Jan 2005: 11 more 'review' articles from WoS
FNISI Export Format
VR1.0
PT J
AU Chastel, C
TI Emergence of new viruses in Asia: is climate change involved?
SO MEDECINE ET MALADIES INFECTIEUSES
AB Tropical Africa is not the only area where deadly viruses have recently emerged. In South-East Asia severe epidemics of dengue hemorrhagic fever started in 1954 and flu pandemics have originated from China such as the Asian flu (H2N2) in 1957, the Hong-Kong flu (H3N2) in 1968, and the Russian flu (H1N1) in 1977. However, it is especially during the last ten years that very dangerous viruses for mankind have repeatedly developed in Asia, with the occurrence of Alkhurma hemorrhagic fever in Saudi Arabia (1995), avian flu (H5N1) in Hong-Kong (1997), Nipah virus encephalitis in Malaysia (1998,) and, above all, the SARS pandemic fever from Southern China (2002). The evolution of these viral diseases was probably not directly affected by climate change. In fact, their emergential success may be better explained by the development of large industry poultry flocks increasing the risks of epizootics, dietary habits, economic and demographic constraints, and negligence in the surveillance and reporting of the first cases. (C) 2004 Elsevier SAS. Tous droits reserves.
PD NOV
PY 2004
VL 34
IS 11
BP 499
EP 505
UT ISI:000225649800002
ER
PT J
AU Krilov, LR
TI Emerging infectious disease issues in international adoptions: severe acute respiratory syndrome (SARS), avian influenza and measles
SO CURRENT OPINION IN INFECTIOUS DISEASES
AB Purpose of review New emerging infections over the last few years demonstrate the potential for the introduction of epidemic illness through global migration. The increasing number of children adopted internationally (>20 000 in 2003, from the United States State Department) provides a unique situation for the spread of emerging infections through the combination of international travel by parents through areas where such infections may be contracted and the nature of the living conditions for many of the orphans being placed by this process.
Recent findings The recent literature on three emerging infections - avian influenza, severe acute respiratory syndrome (SARS) and measles - describes clinical aspects of the illnesses and their epidemiology. For avian influenza aspects of the agrarian economy in southeast Asia enabled the virus to reach the human population. The potential for further adaptation to people could set the stage for a new pandemic. SARS evolved in rural China and spread worldwide in one season with an approximate 10% mortality. Attention to public-health measures led to control of this new illness. Most recently, outbreaks of measles in Chinese orphanages have been documented. These findings demonstrate the potential of such infections to be transmitted during the process of international adoption, and in the case of measles the realization of this potential in recent reported cases from Chinese orphanages brought to the United States on commercial airlines.
Summary Clinicians involved in international adoption and public-health officials assessing emerging infections need to work together in monitoring these issues.
PD OCT
PY 2004
VL 17
IS 5
BP 391
EP 395
UT ISI:000224673700001
ER
PT J
AU Kilbourne, ED
TI Influenza pandemics: Can we prepare for the unpredictable?
SO VIRAL IMMUNOLOGY
AB Although no viruses are better understood or more intensively studied than the viruses of influenza, if the next influenza pandemic occurs within the next 5-10 years its control will depend on innovations in vaccine production developed more than 40 years ago, but not yet applied to the full extent demanded by our present hard-won knowledge of the epidemiology of the disease. We have become so enamored of the brilliant advances made in the interim in understanding the molecular biology of both virus and host that common sense and inexpensive implementation of proven and older methods of control have been neglected as an interim barricade. In this review, I have advocated a return to first principles, while embracing the promise and returns of contemporary research. With the assumption that the next pandemic virus will contain one of the 13 influenza A virus hemagglutinin subtypes not currently causing epidemic human disease, high-yield reassortant viruses of each of these subtypes should be produced with all dispatch and, in collaboration with industry, tested for production stability and immunogenicity in humans. From this archive, an appropriate reassortant could be selected within days or weeks, and production could ensue. If not a perfect match with the imminent pandemic virus, this "barricade vaccine" could stand as a first line of defense until supplanted by a definitive "rampart vaccine," matching better the emergent, potentially pandemic virus.
PD FAL
PY 2004
VL 17
IS 3
BP 350
EP 357
UT ISI:000223940000004
ER
PT J
AU Wood, JM
Robertson, JS
TI From lethal virus to life-saving vaccine: developing inactivated vaccines for pandemic influenza
SO NATURE REVIEWS MICROBIOLOGY
AB Over the past eight years, cases of human infection with highly pathogenic avian influenza viruses have raised international concern that we could be on the brink of a global influenza pandemic. Many of these human infections have proved fatal and if the viruses had been able to transmit efficiently from person to person, the effects would have been devastating. How can we arm ourselves against this pandemic threat when these viruses are too dangerous to use in conventional vaccine production? Recent technological developments (reverse genetics) have allowed us to manipulate the influenza virus genome so that we can construct safe, high-yielding vaccine strains. However, the transition of reverse-genetic technologies from the research laboratory to the manufacturing environment has presented new challenges for vaccine manufacturers as well as veterinary and public health authorities.
PD OCT
PY 2004
VL 2
IS 10
BP 842
EP 847
UT ISI:000224123400016
ER
PT J
AU Capua, I
Alexander, DJ
TI Avian influenza: recent developments
SO AVIAN PATHOLOGY
AB This paper reviews the worldwide situation regarding avian influenza infections in poultry from 1997 to March 2004. The increase in the number of primary introductions and the scientific data available on the molecular basis of pathogenicity have generated concerns particularly for legislative purposes and for international trade. This has led to a new proposed definition of 'avian influenza' to extend all infections caused by H5 and H7 viruses regardless of their virulence as notifiable diseases, although this has encountered some difficulties in being approved.
The paper also reviews the major outbreaks caused by viruses of the H5 or H7 subtype and the control measures applied. The zoonotic aspects of avian influenza, which until 1997 were considered to be of limited relevance in human medicine, are also discussed. The human health implications have now gained importance, both for illness and fatalities that have occurred following natural infection with avian viruses, and for the potential of generating a reassortant virus that could give rise to the next human influenza pandemic.
PD AUG
PY 2004
VL 33
IS 4
BP 393
EP 404
UT ISI:000223975300001
ER
PT J
AU Lipatov, AS
Govorkova, EA
Webby, RJ
Ozaki, H
Peiris, M
Guan, Y
Poon, L
Webster, RG
TI Influenza: Emergence and control
SO JOURNAL OF VIROLOGY
PD SEP
PY 2004
VL 78
IS 17
BP 8951
EP 8959
UT ISI:000223386600001
ER
PT J
AU Tambyah, PA
TI SARS: responding to an unknown virus
SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
AB The severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus which first appeared in southern China at the end of 2002. In early 2003, through a single incident, it spread to Hong Kong, Singapore, Canada and Vietnam. For busy clinicians in large public hospitals, the response to the virus was initially based on ensuring a high level of protection for staff. However, as the epidemic progressed and more information became available about the virus, procedures were rationalized and the virus is currently under control worldwide. There are, however, numerous unanswered questions concerning super-spreading events, the modes of transmission of the virus and, perhaps most importantly, the rapid detection of the virus early in the course of disease. These issues need to be addressed in case the virus becomes more widespread in the near future.
PD AUG
PY 2004
VL 23
IS 8
BP 589
EP 595
UT ISI:000223374800002
ER
PT J
AU Stephenson, I
Nicholson, KG
Wood, JM
Zambon, MC
Katz, JM
TI Confronting the avian influenza threat: vaccine development for a potential pandemic
SO LANCET INFECTIOUS DISEASES
AB Sporadic human infection with avian influenza viruses has raised concern that reassortment between human and avian subtypes could generate viruses of pandemic potential. Vaccination is the principal means to combat the impact of influenza. During an influenza pandemic the immune status of the population would differ from that which exists during interpandemic periods. An emerging pandemic virus will create a surge in worldwide vaccine demand and new approaches in immunisation strategies may be needed to ensure optimum protection of unprimed individuals when vaccine antigen may be limited. The manufacture of vaccines from pathogenic avian influenza viruses by traditional methods is not feasible for safety reasons as well as technical issues. Strategies adopted to overcome these issues include the use of reverse genetic systems to generate reassortant strains, the use of baculovirus-expressed haemagglutinin or related non-pathogenic avian influenza strains, and the use of adjuvants to enhance immunogenicity. In clinical trials, conventional surface-antigen influenza virus vaccines produced from avian viruses have proved poorly immunogenic in immunologically naive populations. Adjuvanted or whole-virus preparations may improve immunogenicity and allow sparing of antigen.
PD AUG
PY 2004
VL 4
IS 8
BP 499
EP 509
UT ISI:000222995900020
ER
PT J
AU Tracey, JP
Woods, R
Roshier, D
West, P
Saunders, GR
TI The role of wild birds in the transmission of avian influenza for Australia: an ecological perspective
SO EMU
AB Waterbirds, particularly Anatidae, are natural reservoirs for low-pathogenic avian influenza and have been implicated as the primary source of infection in outbreaks of highly pathogenic avian influenza. An understanding of the movements of birds and the ecology of avian influenza viruses within the wild bird population is essential in assessing the risks to human health and production industries. Marked differences in the movements of Australian birds from those of the Northern Hemisphere emphasises the danger of generalising trends of disease prevalence to Australian conditions. Populations of Anatidae in Australia are not migratory, as they are in the Northern Hemisphere, but rather display typical nomadic traits, sometimes moving large distances across continental Australia in response to flooding or drought. There is little known regular interchange of anatids between Australia and Asia. In contrast, species such as shorebirds and some seabirds are annual migrants to Australia along recognised flyways from breeding grounds in the Northern Hemisphere. Movement into Australia by these species mainly occurs into the north-west and along the east coast over the Pacific Ocean. These species primarily arrive during the Australian spring and form large aggregations along the coastline and on inland wetlands. Other Australian migratory species (passerines, bee-eaters, dollar-birds, cuckoos, doves) regularly move to and from Asia through the Torres Strait Islands. The disease status of these birds is unknown. The movements of some species, particularly anatids and ardeids, which have ranges including Australia and regions where the virus is known to occur, have been poorly studied and there is potential for introduction of avian influenza subtypes via this route. Avian influenza viruses are highly unpredictable and can undergo reassortment to more pathogenic forms. There is insufficient knowledge of the epidemiology and transmission of these viruses in Australia and broad-scale surveillance of wild birds is logistically difficult. Long-term studies of anatids that co-habit with Charadriiformes are recommended. This would provide an indication of the spatial and temporal patterns of subtypes entering Australia and improve our understanding of the ecology of endemic viruses. Until such time as these data become available, Australia's preparedness for avian influenza must focus on biosecurity at the wild bird-poultry interface.
PY 2004
VL 104
IS 2
BP 109
EP 124
UT ISI:000222199800002
ER
PT J
AU Larski, Z
TI Some new data concerning virology and transmissible spongiform encephalopathies
SO MEDYCYNA WETERYNARYJNA
AB Data presented in this review concern: mechanism for the unusual severity of H5N1 influenza virus, chronic immune activation-a possible lethal factor in HIV infection; induction of T-cell-specific immunity against herpes simplex virus with CpG-peptide complexes; clinical use of feline recombinant omega interferon in cat and in dog; the antiviral activity of non-nucleosidic inhibitors of hepatitis B virus; inhibition of hepatitis B virus in mice by RNA interference; conversion of PrP in the cytosol; proteasome inhibition and TSEs?; monoclonal antibodies inhibit prion replication in vivo; a prion protein epitope selective for PrPSc.
PD JUN
PY 2004
VL 60
IS 6
BP 563
EP 566
UT ISI:000221723100001
ER
PT J
AU Audsley, JM
Tannock, GA
TI The role of cell culture vaccines in the control of the next influenza pandemic
SO EXPERT OPINION ON BIOLOGICAL THERAPY
AB Pandemic influenza A viruses of avian origin are of particular concern and have crossed the species barrier several times in recent years, giving rise to illness and occasionally death in humans. This situation could become dramatically worse if the infectivity of avian viruses for humans were increased by reassortment between the genes of human and avian viruses. Co-infection of humans or an intermediate host with an avian strain and an existing human strain could produce new viruses of unknown pathogenicity to which the entire population would be susceptible. Inactivated vaccines against influenza have been prepared for many years using viruses grown in embryonated chicken eggs. However, the use of eggs presents difficulties when vaccine supplies need to be expanded at short notice. It seems likely that future vaccines will be prepared in high-yielding cell cultures from continuous lines that are preferably anchorage-independent. At present, only certain preparations of the Vero and Madin-Darby canine kidney cell lines, grown and maintained in serum-free medium, are acceptable to all regulatory authorities. However, this situation is likely to change with increasing need for non-pandemic and pandemic vaccines.
PD MAY
PY 2004
VL 4
IS 5
BP 709
EP 717
UT ISI:000221465600010
ER
EF Jan 2004 set:
FNISI Export Format
VR1.0
PT J
AU Webby, RJ
Webster, RG
TI Are we ready for pandemic influenza?
SO SCIENCE
AB During the past year, the public has become keenly aware of the threat of emerging infectious diseases with the global spread of severe acute respiratory syndrome (SARS), the continuing threat of bioterrorism, the proliferation of West Nile virus, and the discovery of human cases of monkeypoxin the United States. At the same time, an old foe has again raised its head, reminding us that our worst nightmare may not be a new one. In 2003, highly pathogenic strains of avian influenza virus, including the H5N1 and H7N7 subtypes, again crossed from birds to humans and caused fatal disease. Direct avian-to-human influenza transmission was unknown before 1997. Have we responded to these threats by better preparing for emerging disease agents, or are we continuing to act only as crises arise? Here we consider progress to date in preparedness for an influenza pandemic and review what remains to be done. We conclude by prioritizing the remaining needs and exploring the reasons for our current lack of preparedness for an influenza pandemic.
PY 2003
PD NOV 28
VL 302
IS 5650
BP 1519
EP 1522
PG 4
UT ISI:000186802200029
ER
PT J
AU Nicholson, KG
Wood, JM
Zambon, M
TI Influenza
SO LANCET
AB Although most influenza infections are self-limited, few other diseases exert such a huge toll of suffering and economic loss. Despite the importance of influenza, there had been, until recently, little advance in its control since amantadine was licensed almost 40 years ago. During the past decade, evidence has accrued on the protection afforded by inactivated vaccines and the safety and efficacy in children of live influenza-virus vaccines. There have been many new developments in vaccine technology. Moreover, work on viral neuraminidase has led to the licensing of potent selective antiviral drugs, and economic decision modelling provides further justification for annual vaccination and a framework for the use of neuraminidase inhibitors. Progress has also been made on developing near-patient testing for influenza that may assist individual diagnosis or the recognition of widespread virus circulation, and so optimise clinical management. Despite these advances, the occurrence of avian H5N1, H9N2, and H7N7 influenza in human beings and the rapid global spread of severe acute respiratory syndrome are reminders of our vulnerability to an emerging pandemic. The contrast between recent cases of H5N1 infection, associated with high mortality, and the typically mild, self-limiting nature of human infections with avian H7N7 and H9N2 influenza shows the gaps in our understanding of molecular correlates of pathogenicity and underlines the need for continuing international research into pandemic influenza. Improvements in animal and human surveillance, new approaches to vaccination, and increasing use of vaccines and antiviral drugs to combat annual influenza outbreaks are essential to reduce the global toll of pandemic and interpandemic influenza.
PY 2003
PD NOV 22
VL 362
IS 9397
BP 1733
EP 1745
PG 13
UT ISI:000186767700023
ER
PT S
AU Weiss, RA
TI Cross-species infections
SO XENO-TRANSPLANTATION
SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY
AB Animals have always been a major source of human infectious disease. Some infections like rabies are recognized as primary zoonoses caused in each case by direct animal-to-human transmission, whereas others like measles become independently sustained within the human population so that the causative virus has diverged from its morbillivirus progenitor in ruminants. Recent examples of direct zoonoses are variant Creutzfeldt-Jakob disease arising from bovine spongiform encephalopathy, and the H5N1 avian influenza outbreak in Hong Kong. Recent epidemic diseases of animal origin are the 1918-1919 influenza pandemic, and the acquired immune deficiency syndrome pandemic caused by human immunodeficiency, virus. Some retroviruses move into and out of the chromosomal DNA of the host germline, so that they may oscillate between being an avirulent inherited Mendelian trait in one species and an infectious pathogen in another. Cross-species viral and other infections are reviewed historically with respect to the evolution of virulence and the concern about iatrogenic enhancement of cross-species transfer by medical procedures akin to xenotransplantation.
PY 2003
VL 278
BP 47
EP 71
PG 25
UT ISI:000185672800003
ER
PT J
AU Baigent, SJ
McCauley, JW
TI Influenza type A in humans, mammals and birds: determinants of virus virulence, host-range and interspecies transmission
SO BIOESSAYS
AB The virulence of a virus is determined by its ability to adversely affect the host cell, host organism or population of host organisms. Influenza A viruses have been responsible for four pandemics of severe human respiratory disease this century. Avian species harbour a large reservoir of influenza virus strains, which can contribute genes to potential new pandemic human strains. The fundamental importance of understanding the role of each of these genes in determining virulence in birds and humans was dramatically emphasised by the recent direct transmission of avian influenza A viruses to humans, causing fatal infection but not community spread. An understanding of the factors involved in transmission between avian and mammalian species should assist in the development of better surveillance strategies for early recognition of influenza A virus strains having human pandemic potential, and possibly in the design of anti-viral strategies. (C) 2003 Wiley Periodicals, Inc.
PY 2003
PD JUL
VL 25
IS 7
BP 657
EP 671
PG 15
UT ISI:000183902700005
ER
PT J
AU Beby-Defaux, A
Giraudeau, G
Bouguermouh, S
Agius, G
TI Influenza: virological aspects, epidemiology and virological diagnosis
SO MEDECINE ET MALADIES INFECTIEUSES
AB Influenza is a major public health issue because of its morbidity and increased mortality observed during epidemics, and because it may develop into a pandemic. A, B and C influenza viruses are RNA segmented viruses with high genetic plasticity including drift leading to new A and B variants responsible for epidemics, and shift resulting in new type A viruses responsible for pandemics. Hemagglutinin and neuraminidase glycoproteins are the targets of neutralizing antibodies. Gene reassortments can occur between human A influenza viruses and the avian reservoir, the pig possibly being an intermediary host. Virulence factors are not well documented, but they might be multigenic. Virological diagnosis is based on direct detection of virus antigens and culture, required for the discovery of new circulating variants in order to adapt vaccinal composition. Influenza epidemiological surveillance is carried out by alert networks. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
PY 2003
PD MAR
VL 33
IS 3
BP 134
EP 142
PG 9
UT ISI:000182998700003
ER
PT J
AU Tollis, M
Di Trani, L
TI Recent developments in avian influenza research: Epidemiology and immunoprophylaxis
SO VETERINARY JOURNAL
AB Influenza A viruses have been isolated from humans, from several other mammalian species and a wide variety of avian species, among which, wild aquatic birds represent the natural hosts of influenza viruses. The majority of the possible combinations of the 15 haemagglutinin (HA) and nine neuraminidase (NA) subtypes recognized have been identified in isolates from domestic and wild birds. Infection of birds can cause a wide range of clinical signs, which may vary according to the host, the virus strain, the host's immune status, the presence of any secondary exacerbating microorganisms and environmental factors. Most infections are inapparent, especially in water-fowl and other wild birds. In contrast, infections caused by viruses of H5 and H7 subtypes can be responsible for devastating epidemics in poultry. Despite the warnings to the poultry industry about these viruses, in 1997 an avian H5N1 influenza virus was directly transmitted from birds to humans in Hong Kong and resulted in 18 confirmed infections, thus strengthening the pandemic threat posed by avian influenza (AI). Indeed, reassortant viruses, harbouring a combination of avian and human viral genomes, have been responsible for major pandemics of human influenza. These considerations warrant the need to continue and broaden efforts in the surveillance of AI. Control programmes have varied from no intervention, as in the case of the occurrence of low pathogenic (LP) AI (LPAI) viruses, to extreme, expensive total quarantine-slaughter programmes carried out to eradicate highly pathogenic (HP) AI (HPAI) viruses. The adoption of a vaccination policy, targeted either to control or to prevent infection in poultry, is generally banned or discouraged. Nevertheless, the need to boost eradication efforts in order to limit further spread of infection and avoid heavy economic losses, and advances in modern vaccine technologies, have prompted a re-evaluation of the potential use of vaccination in poultry as an additional tool in comprehensive disease control strategies. This review presents a synthesis of the most recent research on AI that has contributed to a better understanding of the ecology of the virus and to the development of safe and efficacious vaccines for poultry. (C) 2002 Elsevier Science Ltd. All rights reserved.
PY 2002
PD NOV
VL 164
IS 3
BP 202
EP 215
PG 14
UT ISI:000180614300007
ER
PT J
AU Steinhauer, DA
Skehel, JJ
TI Genetics of influenza viruses
SO ANNUAL REVIEW OF GENETICS
AB Influenza A viruses contain genomes composed of eight separate segments of negative-sense RNA. Circulating human strains are notorious for their tendency to accumulate mutations from one year to the next and cause recurrent epidemics. However, the segmented nature of the genome also allows for the exchange of entire genes between different viral strains. The ability to manipulate influenza gene segments in various combinations in the laboratory has contributed to its being one of the best characterized viruses, and studies on influenza have provided key contributions toward the understanding of various aspects of virology in general, However, the genetic plasticity of influenza viruses also has serious potential implications regarding vaccine design, pathogenicity, and the capacity for novel viruses to emerge from natural reservoirs and cause global pandemics.
PY 2002
VL 36
BP 305
EP 332
PG 28
UT ISI:000180365100012
ER
PT J
AU Stephenson, I
Zambon, M
TI The epidemiology of influenza
SO OCCUPATIONAL MEDICINE-OXFORD
AB Influenza remains a globally important cause of febrile respiratory illness. Influenza virus activity in the community results in significant mortality, morbidity and economic disruption, particularly in those at high risk of developing complications, such as the elderly and those with underlying chronic medical conditions, including pulmonary disease and diabetes mellitus. The occurrence in Hong Kong in 1997 of avian influenza H5N1 in man, which resulted in six deaths, served to remind us of the importance of continuing surveillance and preparation for the next pandemic.
PY 2002
PD AUG
VL 52
IS 5
BP 241
EP 247
PG 7
UT ISI:000177527900003
ER
PT J
AU Ison, MG
Mills, J
Openshaw, P
Zambon, M
Osterhaus, A
Hayden, F
TI Current research on respiratory viral infections: Fourth International Symposium
SO ANTIVIRAL RESEARCH
PY 2002
PD AUG
VL 55
IS 2
BP 227
EP 278
PG 52
UT ISI:000177186000002
ER
PT J
AU Hatta, M
Kawaoka, Y
TI The continued pandemic threat posed by avian influenza viruses in Hong Kong
SO TRENDS IN MICROBIOLOGY
AB In 1997, a highly pathogenic avian H5N1 influenza virus was transmitted directly from live commercial poultry to humans in Hong Kong. Of the 18 people infected, six died. The molecular basis for the high virulence of this virus in mice was found to involve an amino acid change in the PB2 protein. To eliminate the source of the pathogenic virus, all birds in the Hong Kong markets were slaughtered. In 1999, another avian influenza virus of H9N2 subtype was transmitted to two children in Hong Kong. In 2000-2002, H5N1 avian viruses reappeared in the poultry markets of Hong Kong, although they have not infected humans. Continued circulation of H5N1 and other avian viruses in Hong Kong raises the possibility of future human influenza outbreaks. Moreover, the acquisition of properties of human viruses by the avian viruses currently circulating in southeast China might result in a pandemic.
PY 2002
PD JUL
VL 10
IS 7
BP 340
EP 344
PG 5
UT ISI:000176847300012
ER
PT J
AU Capua, I
Alexander, DJ
TI Avian influenza and human health
SO ACTA TROPICA
AB Natural infections with influenza A viruses have been reported in a variety of animal species including humans, pigs, horses, sea mammals, mustelids and birds. Occasionally devastating pandemics occur in humans. Although viruses of relatively few HA and NA subtype combinations have been isolated from mammalian species, all 15 HA subtypes and all 9 NA subtypes, in most combinations, have been isolated from birds.In the 20th century the sudden emergence of antigenically different strains transmissible in humans, termed antigenic shift, has occurred on four occasions, 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1), each time resulting in a pandemic. Genetic analysis of the isolates demonstrated that 'new' strains most certainly emerged after reassortment of genes of viruses of avian and human origin in a permissive host. The leading theory is that the pig represents the 'mixing vessel' where this genetic reassortment may occur.In 1996, an H7N7 influenza virus of avian origin was isolated from a woman with a self-limiting conjunctivitis. During 1997 in Hong Kong, an H5N1 avian influenza virus was recognised as the cause of death of 6 of 18 infected patients. Genetic analysis revealed these human isolates of H5N1 subtype to be indistinguishable from a highly pathogenic avian influenza virus that was endemic in the local poultry population. More recently, in March 1999, two independent isolations of influenza virus subtype H9N2 were made from girls aged one to four who recovered from flu-like illnesses in Hong Kong. Subsequently, five isolations of H9N2 virus from humans on mainland China in August 1998 were reported. H9N2 viruses were known to be widespread in poultry in China and other Asian countries.In all these cases there was no evidence of human to human spread except with the H5N1 infections where there was evidence of very limited spread. This is in keeping with the finding that all these viruses possessed all eight genes of avian origin. It may well be that infection of humans with avian influenza viruses occurs much more frequently than originally assumed, but due to their limited effect go unrecognised.For the human population as a whole the main danger of direct infection with avian influenza viruses appears to be if people infected with an 'avian' virus are infected simultaneously with a 'human' influenza virus. In such circumstances reassortment could occur with the potential emergence of a virus fully capable of spread in the human population, but with antigenic characteristics for which the human population was immunologically naive. Presumably this represents a very rare coincidence, but one which could result in a true influenza pandemic. (C) 2002 Elsevier Science B.V. All rights reserved.
PY 2002
PD JUL
VL 83
IS 1
BP 1
EP 6
PG 6
UT ISI:000176613500001
ER
PT J
AU Mori, I
Yokochi, T
Kimura, Y
TI Role of influenza A virus hemagglutinin in neurovirulence for mammalians
SO MEDICAL MICROBIOLOGY AND IMMUNOLOGY
AB Influenza viruses with potential neuroinvasiveness for humans emerged in Hong Kong in 1997. Prophylactic and therapeutic strategies are urgently needed for controlling the central nervous system complications caused by influenza. Here we review recent advances toward understanding of the possible mechanisms of the neuropathogenesis of influenza virus infection, especially focusing on the role of viral hemagglutinin glycoprotein.
PY 2002
PD MAY
VL 191
IS 1
BP 1
EP 4
PG 4
UT ISI:000176327500001
ER
PT J
AU Varner, AE
TI The increase in allergic respiratory diseases - Survival of the fittest?
SO CHEST
AB The prevalence of allergic respiratory diseases, asthma and allergic rhinoconjunctivitis, has increased since the advent of industrialization. The inverse relationship between the number of infections early in life and atopy has been interpreted as the "hygicne hypothesis." That is, many infections early in life promote the development of T helper type 1 cytokines, while fever infections early in life favor the development of T helper type 2 (Th2) cytokines and atopy. An alternate interpretation of the same data, that atopy is protective against infections early in life, is rarely considered. With epidemiologic, historical, and immunologic data, I suggest that human evolution has favored individuals with an atopic predisposition. Th2 immune responses promote parity, and ensure successful pregnancy and term birth; provide the infant protection against infections and the inflammation induced by common pathogens in the first years of life until the immune system matures; and protect young adults exposed to viral respiratory pathogens. These traits are of particular value with the advent of industrialization, especially so in the era prior to the development of antibiotics. This theory contradicts the assumption that there is no biological or evoltitionary advantage for allergic disease to exist in humans and has significant implications for our current and future treatments of allergic diseases.
PY 2002
PD APR
VL 121
IS 4
BP 1308
EP 1316
PG 13
UT ISI:000175226400046
ER
PT J
AU Zambon, MC
TI The pathogenesis of influenza in humans
SO REVIEWS IN MEDICAL VIROLOGY
AB The rapid evolution of influenza A and B viruses contributes to annual influenza epidemics in humans. In addition, pandemics of influenza are also caused by influenza A viruses, whereas influenza B does not have the potential to cause pandemics because there is no animal reservoir of the virus. Study of the genetic differences between influenza A and influenza B viruses, which are restricted to humans, may be informative in understanding the factors that govern mammalian adaptation of influenza A viruses.Aquatic birds provide the natural reservoir for influenza A viruses, but in general, avian influenza is asymptomatic in feral birds. Occasionally, however, highly pathogenic strains of influenza cause serious systemic infections in domestic poultry. The pathogenicity of these strains is related to the presence of a polybasic cleavage sequence in the precursor of the surface glycoprotein haemagglutinin, which makes the glycoprotein susceptible to activation by ubiquitous proteases such as furin and PC6.However, the mechanism of pathogenicity may differ in highly pathogenic strains of human influenza, such as the H1N1 pandemic strain of 1918 and the H5N1 strain involved in the outbreak in Hong Kong in 1997. Binding of host proteases by the viral neuraminidase to assist activation of the haemagglutinin, shortening of the neuraminidase and substitutions in the polymerase gene, PB2, have all been suggested as alternative molecular correlates of pathogenicity of human influenza viruses. Additionally, systemic spread in humans of pathogenic subtypes has not been demonstrated and host factors such as interferons may be crucial in preventing the spread of the virus outside the respiratory tract. Copyright (C) 2001 John Wiley & Sons, Ltd.
PY 2001
PD JUL-AUG
VL 11
IS 4
BP 227
EP 241
PG 15
UT ISI:000170106600004
ER
PT J
AU Stephenson, I
Nicholson, KG
TI Influenza: vaccination and treatment
SO EUROPEAN RESPIRATORY JOURNAL
AB Few conditions exert such an enormous toll of absenteeism, suffering, medical consultations, hospitalization, death and economic loss as influenza. Patients at high risk of complications and mortality include the elderly and those with pre-existing cardiopulmonary disease.The outbreak in 1997 in Hong Kong, of avian H5N1 influenza in man, which resulted in six deaths among 18 hospitalized cases, and the recent isolation of H9N2 viruses from two children in Hong Kong, are reminders that preparation must be made for the next pandemic, Since the 1970s, efforts to control influenza have mostly focussed on the split product and surface antigen vaccines. These vaccines are of proven efficacy in healthy adults and are effective in elderly people with and without medical conditions putting them at high risk of complications and death following influenza infection,However, vaccine coverage is patchy and often low, and outbreaks of influenza are not uncommon in well-immunized residents of nursing homes. New vaccines and methods of vaccine delivery are being del eloped in attempts to overcome the limitations of existing vaccines.The antiviral drugs amantadine and rimantadine were developed in the 1960s, but have not been used widely due to their spectrum of activity, rapid emergence of resistance, and adverse effects associated with amantadine, The site of enzyme activity of the influenza neuraminidase is highly conserved between types, subtypes and strains of influenza and has emerged as the target of an exciting new class of antiviral agents that are effective both prophylactically and as therapy.
PY 2001
PD JUN
VL 17
IS 6
BP 1282
EP 1293
PG 12
UT ISI:000169967700035
ER
PT J
AU Horimoto, T
Kawaoka, Y
TI Pandemic threat posed by avian influenza A viruses
SO CLINICAL MICROBIOLOGY REVIEWS
AB Influenza pandemics, defined as global outbreaks of the disease due to viruses with new antigenic subtypes, have exacted high death tolls from human populations. The last two pandemics were caused by hybrid viruses, or reassortants, that harbored a combination of avian and human viral genes. Avian influenza viruses are therefore key contributors to the emergence of human influenza pandemics. In 1997 an H5N1 influenza virus was directly transmitted from birds in live poultry markets in Hong Kong to humans. Eighteen people were infected in this outbreak, six of whom died. This avian virus exhibited high virulence in both avian and mammalian species, causing systemic infection in both chickens and mice. Subsequently, another avian virus with the H9N2 subtype was directly transmitted from birds to humans in Hong Kong. Interestingly, the genes encoding the internal proteins of the H9N2 virus are genetically highly related to those of the H5N1 virus, suggesting a unique property of these gene products. The identification of avian viruses in humans underscores the potential of these and similar strains to produce devastating influenza outbreaks in major population centers. Although highly pathogenic avian influenza viruses had been identified before the 1997 outbreak in Hong Kong, their devastating effects had been confined to poultry. With the Hong Kong outbreak, it became clear that the virulence potential of these viruses extended to humans.
PY 2001
PD JAN
VL 14
IS 1
BP 129
EP +
PG 22
UT ISI:000166436100007
ER
PT J
AU Luscher-Mattli, M
TI Influenza chemotherapy: a review of the present state of art and of new drugs in development
SO ARCHIVES OF VIROLOGY
AB Influenza is worldwide one of the deadliest infectious diseases. Lethal influenza mutants can unpredictably arise, as in the 1918 pandemic, or in the 1997 I-long Kong influenza outbreak. Vaccines are today the only protective prophylactic agents, and development of potent new anti-influenza drugs of therapeutic effectiveness appears urgent.It is the aim of the present review, to summarize and discuss the different investigational approaches to this goal. In Medline- and several internet virology database-searches, numerous citations were compiled, and selected according to their relevance to the different topics discussed.The antiviral agents are classified according to their target in the viral replication cycle: proteolytic activation of haemagglutinin, attachment of the virus to specific cell-surface receptors, endocytosis and fusion with the endosomal membrane, uncoating of the nucleocapsid, multiplication, i.e. synthesis of viral RNA and mRNA, and release of the new virus generation from the host cell surface.Potential drugs, directed towards each of these replication steps are described with respect to their mechanism of action, antiviral activity, toxic side effects and induction of resistance. The most promising candidates for safe and potent new influenza drugs, are antiviral agents, directed towards a virus-specific, well conserved target, such as inhibitors of virus-cell fusion, inhibitors of RNA transcriptase and endonuclease, and inhibitors of neuraminidase.It can be hoped that in the near future potent and therapeutically effective anti-influenza drugs will be available.influenza belongs to the class of Orthomyxoviridae. Three subtypes of influenza viruses (A. B and C) are distinguished, influenza A being the most common source of epidemics or pandemics: this subtype can affect humans, other mammalian and avian species, and is genetically extremely variable (antigenic shifts or drifts). By reassortment of genes during virus replication- either with other human influenza virus types or with avian or swine virus genetic material, new reassortant virus strains are produced [30, 35, 65, 74]. The resulting new virus strain is not recognized by the human immune system, and may cause unpredictable and severe epidemic or even pandemic influenza outbreaks.The most lethal pandemic of 1918 (with over 20 millions of deaths) was followed by several more recent influenza epidemics [15, 19, 22, 57], all clearly associated with the appearance of new influenza A strains. Ln the 1997 Hong Kong influenza outbreak, the appearance of an avian (H5N1) virus was - for the first time - observed in humans [9]. In an attempt to control and prevent highly lethal pandemics, a global program for influenza surveillance was initiated by the World Health Organization (WHO) in 1947.Epidemics spread rapidly from country to country, in some cases with alarming speed: one to six months for the 1968 Hong Kong- and the Russian flu of 1977, respectively [15]. Due to increased global traveling and trading, this spread can be expected to be even faster in the future.In a moderate influenza year, globally as many as 500 million people are affected by the disease, and annually 20-40 000 deadly flu infections were registered in the US [19]. Despite these facts, influenza appears to be an underestimated public health problem, and HIV remains the predominant target for antiviral research [3].
PY 2000
VL 145
IS 11
BP 2233
EP 2248
PG 16
UT ISI:000166018500001
ER
PT J
AU Subbarao, K
Katz, J
TI Avian influenza viruses infecting humans
SO CELLULAR AND MOLECULAR LIFE SCIENCES
AB Avian species, particularly waterfowl, are the natural hosts Of influenza A viruses. Influenza viruses bearing each of the 15 hemagglutinin and nine neuraminidase subtypes infect birds and serve as a reservoir from which influenza viruses or genes are introduced into the human population. Viruses with novel hemagglutinin genes derived from avian influenza viruses, with or without other accompanying avian influenza virus genes, have the potential for pandemic spread when the human population lacks protective immunity against the new hemagglutinin. Avian influenza viruses were thought to be limited in their ability to directly infect humans until 1997, when 18 human infections with avian influenza H5N1 viruses occurred in Hong Kong. In 1999, two human infections with avian influenza H9N2 viruses Ts ere also identified in Hong Kong. These events established that avian viruses could infect humans without acquiring human influenza genes by reassortment in an intermediate host and highlighted challenges associated with the detection of human immune responses to avian influenza viruses and the development of appropriate vaccines.
PY 2000
PD NOV
VL 57
IS 12
BP 1770
EP 1784
PG 15
UT ISI:000165691100009
ER
PT J
AU Skehel, JJ
Wiley, DC
TI Receptor binding and membrane fusion in virus entry: The influenza hemagglutinin
SO ANNUAL REVIEW OF BIOCHEMISTRY
AB Hemagglutinin (HA) is the receptor-binding and membrane fusion glycoprotein of influenza virus and the target for infectivity-neutralizing antibodies. The structures of three conformations of the ectodomain of the 1968 Hong Kong influenza virus HA have been determined by X-ray crystallography: the single-chain precursor, HA0; the metastable neutral-pH conformation found on virus, and the fusion pH-induced conformation. These structures provide a framework for designing and interpreting the results of experiments on the activity of HA in receptor binding, the generation of emerging and reemerging epidemics, and membrane fusion during viral entry.
PY 2000
VL 69
BP 531
EP 569
PG 39
UT ISI:000089735700018
ER
PT J
AU Subbarao, K
Shaw, MW
TI Molecular aspects of avian influenza (H5N1) viruses isolated from humans
SO REVIEWS IN MEDICAL VIROLOGY
AB In 1997, 18 human infections with H5N1 influenza type A were identified in Hong Kong and six of the patients died. There were concomitant outbreaks of H5N1 infections in poultry. The gene segments of the human H5N1 viruses were derived from avian influenza A viruses and not from circulating human influenza A viruses, in 1999 two cases of human infections caused by avian H9N2 virus were also identified in Hong Kong. These events established that avian influenza viruses can infect humans without passage through an intermediate host and without acquiring gene segments from human influenza viruses. The likely origin of the H5N1 viruses has been deduced from molecular analysis of these and other viruses isolated from the region. The gene sequences of the H5N1 viruses were analysed in order to identify the molecular basis for the ability of these avian viruses to infect humans. Copyright (C) 2000 John Wiley & Sons, Ltd.
PY 2000
PD SEP-OCT
VL 10
IS 5
BP 337
EP 348
PG 12
UT ISI:000089517300007
ER
PT J
AU Swayne, DE
Suarez, DL
TI Highly pathogenic avian influenza
SO REVUE SCIENTIFIQUE ET TECHNIQUE DE L OFFICE INTERNATIONAL DES EPIZOOTIES
AB Highly pathogenic (HP) avian influenza (Al) (HPAI) is an extremely contagious, multi-organ systemic disease of poultry leading to high mortality, and caused by some H5 and H7 subtypes of type A influenza virus, family Orthomyxoviridae. However, most Al virus strains are mildly pathogenic (MP) and produce either subclinical infections or respiratory and/or reproductive diseases in a variety of domestic and wild bird species. Highly pathogenic avian influenza is a List A disease of the Office International des Epizooties, while MPAI is neither a List A nor List B disease. Eighteen outbreaks of HPAI have been documented since the identification of Al virus as the cause of fowl plague in 1955.Mildly pathogenic avian influenza viruses are maintained in wild aquatic bird reservoirs, occasionally crossing over to domestic poultry and causing outbreaks of mild disease. Highly pathogenic avian influenza viruses do not have a recognised wild bird reservoir, but can occasionally be isolated from wild birds during outbreaks in domestic poultry, Highly pathogenic avian influenza viruses have been documented to arise from MPAI viruses through mutations in the haemagglutinin surface protein.Prevention of exposure to the virus and eradication are the accepted methods for dealing with HPAI. Control programmes, which imply allowing a low incidence of infection, are not an acceptable method for managing HPAI, but have been used during some outbreaks of MPAI. The components of a strategy to deal with MPAI or HPAI include surveillance and diagnosis, biosecurity, education, quarantine and depopulation, Vaccination has been used in some control and eradication programmes for Al.
PY 2000
PD AUG
VL 19
IS 2
BP 463
EP 482
PG 20
UT ISI:000088194900009
ER
PT J
AU de Jong, JC
Rimmelzwaan, GF
Fouchier, RAM
Osterhaus, ADME
TI Influenza virus: a master of metamorphosis
SO JOURNAL OF INFECTION
PY 2000
PD MAY
VL 40
IS 3
BP 218
EP 228
PG 11
UT ISI:000087992300002
ER
PT J
AU Zientara, S
Legay, V
TI Emerging viral zoonoses
SO POINT VETERINAIRE
AB The concept of emerging diseases has become apparent in the last twenty years. The concept includes newly discovered diseases and other older diseases. which were thought to be controlled but which, for a variety of reasons, are now re-appearing. It includes influenza viruses such as avian nu H5N1, Borna virus, West Nile, Hantavirus and the morbilliviruses (3 tables, figures,40 references).
PY 2000
PD MAY
VL 31
IS 207
BP 23
EP 30
PG 8
UT ISI:000087437600006
ER
PT J
AU Cox, NJ
Subbarao, K
TI Global epidemiology of influenza: Past and present
SO ANNUAL REVIEW OF MEDICINE
AB Pandemics are the most dramatic presentation of influenza. Three have occurred in the twentieth century: the 1918 H1N1 pandemic, the 1957 H2N2 pandemic, and the 1968 H3N2 pandemic. The tools of molecular epidemiology have been applied in an attempt to determine the origin of pandemic viruses and to understand what made them such successful pathogens. An excellent example of this avenue of research is the recent phylogenetic analysis of genes of the virus that caused the devastating 1918 pandemic. This analysis has been used to identify evolutionarily related influenza virus genes as a clue to the source of the pandemic of 1918. Molecular methods have been used to investigate the avian H5N1 and H9N2 influenza viruses that recently infected humans in Hong Kong. Antigenic, genetic, and epidemiologic analyses have also furthered our understanding of interpandemic influenza. Although many questions remain, advances of the past two decades have demonstrated that several widely held concepts concerning the global epidemiology of influenza were false.
PY 2000
VL 51
BP 407
EP 421
PG 15
UT ISI:000086339800025
ER
PT J
AU Alexander, DJ
Brown, IH
TI Recent zoonoses caused by influenza A viruses
SO REVUE SCIENTIFIQUE ET TECHNIQUE DE L OFFICE INTERNATIONAL DES EPIZOOTIES
AB Influenza is a highly contagious, acute illness which has afflicted humans and animals since ancient times. Influenza viruses are part of the Orthomyxoviridae family and are grouped into types A, B and C according to antigenic characteristics of the core proteins. Influenza A viruses infect a large variety of animal species, including humans, pigs, horses, sea mammals and birds, occasionally producing devastating pandemics in humans, such as in 1918, when over twenty million deaths occurred world-wide. The two surface glycoproteins of the virus, haemagglutinin (HA) and neuraminidase (NA), are the most important antigens for inducing protective immunity in the host and therefore show the greatest variation. For influenza A viruses, fifteen antigenically distinct HA subtypes and nine NA subtypes are recognised at present; a virus possesses one HA and one NA subtype, apparently in any combination. Although viruses of relatively few subtype combinations have been isolated from mammalian species, all subtypes, in most combinations, have been isolated from birds. In the 20th Century, the sudden emergence of antigenically different strains in humans, termed antigenic shift, has occurred on four occasions, as follows, in 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1), each resulting in a pandemic. Frequent epidemics have occurred between the pandemics as a result of gradual antigenic change in the prevalent virus, termed antigenic drift. Currently, epidemics occur throughout the world in the human population due to infection with influenza A Viruses of subtypes H1N1 and H3N2 or with influenza B virus. The impact of these epidemics is most effectively measured by monitoring excess mortality due to pneumonia and influenza. Phylogenetic studies suggest that aquatic birds could be the source of all influenza A viruses in other species. Human pandemic strains are thought to have emerged through one of the following three mechanisms:genetic reassortment (occurring as a result of the segmented genome of the virus) of avian and human influenza A viruses infecting the same hostdirect transfer of whole virus from another speciesthe re-emergence of a virus which may have caused an epidemic many years earlier.Since 1996, the viruses H7N7, H5N1 and H9N2 have been transmitted from birds to humans but have apparently failed to spread in the human population. Such incidents are rare, but transmission between humans and other animals has also been demonstrated. This has led to the suggestion that the proposed reassortment of human and avian viruses occurs in an intermediate animal with subsequent transference to the human population. Pigs have been considered the leading contender for the role of intermediary because these animals may serve as hosts for productive infections of both avian and human viruses and, in addition, the evidence strongly suggests that pigs have been involved in interspecies transmission of influenza viruses, particularly the spread of H1N1 viruses to humans. Global surveillance of influenza is maintained by a network of laboratories sponsored by the World Health Organization. The main control measure for influenza in human populations is immunoprophylaxis, aimed at the epidemics occurring between pandemics.
PY 2000
PD APR
VL 19
IS 1
BP 197
EP 225
PG 29
UT ISI:000086242500018
ER
PT J
AU Demicheli, V
Jefferson, T
Rivetti, D
Deeks, J
TI Prevention and early treatment of influenza in healthy adults
SO VACCINE
AB Introduction: We present three systematic reviews carried out within the Cochrane Collaboration, focusing on a different influenza intervention in healthy adults: Vaccines; Ion Channel Inhibitor antivirals and Neuraminidase Inhibitor (NIs) antivirals. The objectives were to identify, retrieve and assess all studies evaluating the effects of these interventions in prophylaxis and early treatments of influenza and the frequency of adverse events. Additionally we present the results of the economic evaluation of effective alternatives in order to define the most cost-effective intervention. The economic evaluation is set in the context of the British Army.Methods: Studies were identified using a standard Cochrane search strategy. Any randomised or quasi-randomised studies in healthy individuals aged 14-60 years were considered for inclusion in the systematic review. Those which met inclusion criteria were assessed for quality and their data meta-analysed. The economic model was constructed using Cost-effectiveness and Cost-utility study designs,Results: Live aerosol vaccines reduced cases of clinical influenza A with virological confirmation (by serology and/or viral isolation) by 48% (95%CI, 24-64%), whilst recommended inactivated parenteral vaccines have an efficacy of 68% (95%CI, 49-79%). Vaccine effectiveness in reducing clinical influenza cases (i.e. without virological confirmation) was lower, with efficacies of 13 and 24% respectively. Use of the vaccine significantly reduced time off work, but only by 0.4 days (95%CI, 0.1-0.8 days). Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. When compared to placebo for the prevention of influenza, oral amantadine was 61% (95%CI: 51-69%) efficacious (RR 0.39 - 95%CI: 0.31-0.49), and oral rimantadine was 64% (95%CI: 41-78%) efficacious (RR 0.36 - 95%CI: 0.22-0.59), When compared to placebo for the treatment of influenza, oral amantadine significantly shortened duration of fever (by 1.00 days - 95%CI: 0.73-1.29), and oral rimantadine significantly shortened duration of fever (by 1.27 days - 95%CI: 0.77-1.77), When compared to placebo, NIs were 74% (95%CIs: 50-87%) effective in preventing naturally occurring cases of clinically defined influenza. In a treatment role, NIs shortened the duration of symptoms by one day (Weighted Mean Difference - 1.0; 95%CIs: -1.3 to - 0.6) when a clinical case definition is used. The economic results show that in healthy adults, inactivated vaccines appear the best buy.Conclusions: If assessed from the point of view of effectiveness and efficiency, vaccines are undoubtedly the best preventive means for clinical influenza in healthy adults. However, when safety and quality of life considerations are included, parenteral vaccines hate such low effectiveness and high incidence of trivial local adverse effects that the trade-off is unfavourable, This is so even when the incidence of influenza is high and adverse effect quality of life preferences are rated low. We reached similar conclusions for antivirals and NIs even at high influenza incidence levels. On current evidence we conclude in healthy adults aged 14-60 the most cost-effective option is not to take any action. (C) 2000 Elsevier Science Ltd. All rights reserved.
PY 2000
PD JAN 6
VL 18
IS 11-12
BP 957
EP 1030
PG 74
UT ISI:000084600000001
ER
PT J
AU Steinhauer, DA
TI Role of hemagglutinin cleavage for the pathogenicity of influenza virus
SO VIROLOGY
AB Although human epidemics of influenza occur on nearly an annual basis and result in a significant number of "excess deaths," the viruses responsible are not generally considered highly pathogenic. On occasion, however, an outbreak occurs that demonstrates the potential lethality of influenza viruses. The human pandemic of 1918 spread worldwide and killed millions, and the limited human outbreak of highly pathogenic avian viruses in Hong Kong at the end of 1997 is a warning that this could happen again. In avian species such as chickens and turkeys, several outbreaks of highly pathogenic influenza viruses have been documented. Although the reason for the lethality of the human 1918 viruses remains unclear, the pathogenicity of the avian viruses, including those that caused the human 1997 outbreak, relates primarily to properties of the hemagglutinin glycoprotein (HA). Cleavage of the HA precursor molecule HA, is required to activate virus infectivity, and the distribution of activating proteases in the host is one of the determinants of tropism and, as such, pathogenicity. The HAs of mammalian and nonpathogenic avian viruses are cleaved extracellularly, which limits their spread in hosts to tissues where the appropriate proteases are encountered. On the other hand, the HAs of pathogenic viruses are cleaved intracellularly by ubiquitously occurring proteases and therefore have the capacity to infect various cell types and cause systemic infections. The x-ray crystal structure of HA, has been solved recently and shows that the cleavage site forms a loop that extends from the surface of the molecule, and it is the composition and structure of the cleavage loop region that dictate the range of proteases that can potentially activate infectivity, Here influenza virus pathogenicity is discussed, with an emphasis on the role of HA, cleavage as a determining factor. (C) 1999 Academic Press.
PY 1999
PD MAY 25
VL 258
IS 1
BP 1
EP 20
PG 20
UT ISI:000080592400001
ER
PT J
AU Mendel, DB
Roberts, NA
TI In-vitro and in-vivo efficacy of influenza neuraminidase inhibitors
SO CURRENT OPINION IN INFECTIOUS DISEASES
AB Influenza continues to be a major health concern and there is always the threat of a pandemic due to the emergence of a viral strain new to the human population, as exemplified by the avian influenza A/H5N1 virus which was responsible for six deaths in Hong Kong last year. Data reported in the past year, based on in-vitro, in-vivo (animal) and clinical studies, suggest that a new class of antiviral compounds targeting the viral neuraminidase is likely to be useful for the treatment and prevention of influenza virus infections in humans. Curr Opin Infect Dis 11:727-732, (C) 1998 Lippincott Williams & Wilkins.
PY 1998
PD DEC
VL 11
IS 6
BP 727
EP 732
PG 6
UT ISI:000077917900013
ER
PT J
AU Boibieux, A
Bouhour, D
Biron, F
Chidiac, C
Peyramond, D
TI Avian influenza in Hong Kong
SO MEDECINE ET MALADIES INFECTIEUSES
AB The first human case of avian influenza type A(H5N1) occured in a 3-year-old child who died from respiratory failure in May 1997, in Hong Kong, even though human cells are known not to have receptors for avian influenza viruses. By January 6, 1998, 16 confirmed and 3 suspected cases had been identified in Hong Kong. initial antigenic and genetic analyses suggest multiple introductions in humans from poultry sources. Al this time, epidemiological studies Indicate that the virus not being efficiently transmitted among humans. However a pandemic of avian influenza remains possible and global surveillance for influenza viruses is essential.
PY 1998
PD FEB
VL 28
IS 2
BP 193
EP 194
PG 2
UT ISI:000073006400002
ER
EF