Host-range barrier of influenza A viruses

Ample evidence suggests that all influenza viruses in mammals were probably derived from those in wild waterfowl at some time. In addition to those already established in mammals, the viruses have been transmitted to both mammals and to poultry from wild waterfowl and caused outbreaks in recent years. Experimentally, however, the viruses from one species of animals do not grow efficiently in other species. For example, human influenza viruses do not replicate in ducks or in horses, indicating their host range restriction. This paper reviews current knowledge on the host-range restriction of influenza viruses, focusing on the role of the hemagglutinin (HA).     

Type A influenza viruses in waterfowl in Ohio and implications for domestic turkeys

Because ducks are considered an important reservoir for type A influenza virus, and type A influenza viruses had not been recovered from ducks in Ohio, a 3-year virus surveillance study was conducted in Ohio waterfowl and waterfowl passing through Ohio to determine if domestic turkeys were at risk of exposure to avian influenza (AI) viruses from the waterfowl reservoir. The prevalence of AI infections in ducks during the fall migration averaged about 5.9%. The 55 waterfowl-origin type A influenza viruses recovered from ducks during fall 1986, 1987, and 1988 represented 23 different hemagglutinin-neuraminidase sub-type combinations of type A influenza viruses. Virus recovery frequencies ranged from 3.6% to 7.8% between years, from 2.0% to 8.2% between study sites, from 0.0% to 16.7% for sampling days, and from 0.0% to 14.3% among species of ducks sampled.     

Influenza virus infections in mammals

The natural reservoir of all known subtypes of influenza A viruses are aquatic birds, mainly of the orders Anseriformes and Charadriiformes in which the infection is asymptomatic and the viruses stay at an evolutionary equilibrium. However, mammals may occasionally contract influenza A virus infections from this pool. This article summarizes: (i) natural infections in mammals including pigs, horses, marine mammals, ferrets, minks; (ii) results from experimental infections in several animal models including mice, ferrets, primates, rats, minks, hamsters and (iii) evidence for the increased pathogenicity of the current influenza A H5N1/Asia viruses for mammals. Several reports have shown that a number of mammalian species, including pigs, cats, ferrets, minks, whales, seals and finally also man are susceptible to natural infection with influenza A viruses of purely avian genetic make up. Among the mammalian species naturally susceptible to avian influenza virus the pig and the cat might exert the greatest potential public health impact. Despite numerous studies in animal and cell culture models, the basis of the extended host spectrum and the unusual pathogenicity of the influenza A H5N1 viruses for mammals is only beginning to be unraveled. Recently, also the transmission of equine influenza A virus to greyhound racing dogs has been documented.     

Intracerebral pathogenicity for chickens of avian influenza viruses isolated from free-living waterfowl in Japan

The pathogenicity for chickens of 91 strains of avian influenza A virus isolated from such free-living waterfowl as whistling swan, pintail, tufted duck, mallard and black-tailed gull in Japan was tested. The majority of the virus strains infected and were pathogenic for the chickens. The virulence of these viruses seemed not to be as high as that of fowl plague virus. There were no significant differences in the intracerebral index score among the viruses belonging to the same subtype, irrespective of year of isolation or host.     

Using mean infectious dose of high- and low-pathogenicity avian influenza viruses originating from wild duck and poultry as one measure of infectivity and adaptation to poultry

The mean infectious doses of selected avian influenza virus (AIV) isolates, determined in domestic poultry under experimental conditions, were shown to be both host-dependent and virus strain-dependent and could be considered one measure of the infectivity and adaptation to a specific host. As such, the mean infectious dose could serve as a quantitative predictor for which strains of AIV, given the right conditions, would be more likely transmitted to and maintained in a given species or subsequently cause an AI outbreak in the given species. The intranasal (IN) mean bird infectious doses (BID50) were determined for 11 high-pathogenicity AIV (HPAIV) isolates of turkey and chicken origin for white leghorn (WL) chickens, and for low-pathogenicity AIV (LPAIV) isolates of chicken (n = 1) and wild mallards (n = 2) for turkeys, and WL and white Plymouth rock (WPR) chickens, domestic ducks and geese, and Japanese quail. The BID50 for HPAIV isolates for WL chickens ranged from 10(1.2) to 10(4.7) mean embryo infectious dose (EID50) (median = 10(2.9)). For chicken-origin HPAIV isolates, the BID50 in WL chickens ranged from 10(1.2) to 10(3.0) EID50 (median = 10(2.6)), whereas for HPAIV isolates of turkey origin, the BID50 in WL chickens was higher, ranging from 10(2.8) to 10(4.7) EID50 (median = 10(3.9)). The BID50 of 10(4.7) was for a turkey-origin HPAIV virus that was not transmitted to chickens on the same farm, suggesting that, under the specific conditions present on that farm, there was insufficient infectivity, adaptation, or exposure to that virus population for sustained chicken transmission. Although the upper BID50 limit for predicting infectivity and sustainable transmissibility for a specific species is unknown, a BID50 < 10(4.7) was suggestive of such transmissibility. For the LPAIVs, there was a trend for domestic ducks and geese and Japanese quail to have the greatest susceptible and for WL chickens to be the most resistant, but turkeys were susceptible to two LPAIV tested when used at moderate challenge doses. This suggests domestic ducks and geese, turkeys, and Japanese quail could serve as bridging species for LPAIVs from wild waterfowl to chickens and other gallinaceous poultry. These data do provide support for the commonly held and intuitive belief that mixing of poultry species during rearing and in outdoor production systems is a major risk factor for interspecies transmission of AIVs and for the emergence of new AIV strains capable of causing AI outbreaks because these situations present a more diverse host population to circumvent the natural host dependency or host range of circulating viruses.     

Review of the literature on avian influenza A viruses in pigeons and experimental studies on the susceptibility of domestic pigeons to influenza A viruses of the haemagglutinin subtype H7

The scientific literature of the past century is reviewed on fowl plague (presently termed highly pathogenic avian influenza, HPAI) in pigeons. HPAI viruses cause epidemic disease outbreaks with high rates of losses in many avian species, particularily in chickens and turkeys. Also susceptible to disease are quails, guinea fowl, ducks, geese, ostriches, passerine birds, and birds of prey whereas conflicting reports on the susceptibility of the domestic pigeon exist. Based on literature reports and on own experiments, and applying as criteria for judgements clinically overt forms of disease, virus multiplication plus shedding and seroconversion, it is concluded that domestic pigeons are only partially susceptible to influenza A viruses of the haemagglutinin subtype H7. Infection of pigeons with H7 viruses results only in some of them in signs, virus shedding and seroconversion. Using the same criteria, pigeons appear to be even less susceptible to infection with influenza A viruses of the H5 subtype. Only one of five publications describe in 1/19 pigeons exposed to H5 influenza A virus depression one day before death, and only 2/19 multiplied and excreted virus, and 1/19 developed circulating antibodies. Consequently, pigeons play only a minor role in the epidemiology of H5 influenza viruses. In contrast, following infection with influenza A virus of the subtype H7 clinical signs in pigeons consist of conjunctivitis, tremor, paresis of wings and legs, and wet droppings. H7-infected pigeons multiply and excrete H7 viruses and develop circulating antibodies. Albeit of the status of infection, free-flying domestic pigeons can act as mechanical vectors and vehicles for long-distance transmission of any influenza A virus if plumage or feet were contaminated.     

Epidemiological findings of outbreaks of disease caused by highly pathogenic H5N1 avian influenza virus in poultry in Egypt during 2006

This paper describes the first threats of H5N1 avian influenza outbreaks in Egypt recorded from February to December 2006 in commercial and domestic poultry from different species and summarizes the major characteristics of the outbreak. There were 1024 cases from different poultry species (rural and commercial chickens of different breeding types, turkeys, ducks, geese, and quail) either in commercial breeding or in backyards from different locations in Egypt. All tested positive for the H5N1 subtype. From these cases only 12 avian influenza A viruses were isolated and characterized from samples collected during outbreaks. All isolates were characterized, and the data confirmed that the isolated viruses belong to highly pathogenic avian influenza of subtype H5N1. Full hemagglutinin (HA) gene (segment 4) sequencing was also done, and the sequences of these isolates were compared with other strains from Russia, Africa, and the Middle East. The data revealed that all Egyptian strains were very closely related and belonging to subclade 2.2 of the H5N1 virus of Eurasian origin, the same one circulating in the Middle East region and introduced into Africa at the beginning of 2006. This study showed evidence of the wide spread of H5N1 virus infection in domestic poultry in Egypt within a short time. The most obvious features of these outbreaks were severe clinical signs and high mortalities as well as very rapid and widespread occurrence within the country in a very short time. The possible causes of its rapid spread and prospects of disease control are discussed.     

A review of avian influenza in different bird species

Only type A influenza viruses are known to cause natural infections in birds, but viruses of all 15 haemagglutinin and all nine neuraminidase influenza A subtypes in the majority of possible combinations have been isolated from avian species. Influenza A viruses infecting poultry can be divided into two distinct groups on the basis of their ability to cause disease. The very virulent viruses cause highly pathogenic avian influenza (HPAI), in which mortality may be as high as 100%. These viruses have been restricted to subtypes H5 and H7, although not all viruses of these subtypes cause HPAI. All other viruses cause a much milder, primarily respiratory disease, which may be exacerbated by other infections or environmental conditions. Since 1959, primary outbreaks of HPAI in poultry have been reported 17 times (eight since 1990), five in turkeys and 12 in chickens. HPAI viruses are rarely isolated from wild birds, but extremely high isolation rates of viruses of low virulence for poultry have been recorded in surveillance studies, giving overall figures of about 15% for ducks and geese and around 2% for all other species. Influenza viruses have been shown to affect all types of domestic or captive birds in all areas of the world, but the frequency with which primary infections occur in any type of bird depends on the degree of contact there is with feral birds. Secondary spread is usually associated with human involvement, probably by transferring infective faeces from infected to susceptible birds.     

Influenza virus surveillance in waterfowl in Pennsylvania after the H5N2 avian outbreak

During the latter stages of the lethal H5N2 influenza eradication program in domestic poultry in Pennsylvania in 1983-84, surveillance of waterfowl was done to determine if these birds harbored influenza viruses that might subsequently appear in poultry. From late June to November 1984, 182 hemagglutinating viruses were isolated from 2043 wild birds, primarily ducks, in the same geographical area as the earlier lethal H5N2 avian influenza outbreak. The virus isolates from waterfowl included paramyxoviruses (PMV-1, -4, and -6) and influenza viruses of 13 antigenic combinations. There was only one H5N2 isolate from a duck. Although this virus was antigenically related to the lethal H5N2 virus, genetic and antigenic analysis indicated that it could be discriminated from the virulent family of H5N2 viruses, and it did not originate from chickens. Many of the influenza viruses obtained from wild ducks were capable of replicating in chickens after experimental inoculation but did not cause disease. These studies show that many influenza A virus strains circulating in waterfowl in the vicinity of domestic poultry in Pennsylvania did not originate from domestic poultry. These influenza viruses from wild ducks were capable of infecting poultry; however, transmission of these viruses to poultry apparently was avoided by good husbandry and control measures.     

Vaccines protect chickens against H5 highly pathogenic avian influenza in the face of genetic changes in field viruses over multiple years

Inactivated whole avian influenza (AI) virus vaccines, baculovirus-derived AI haemagglutinin vaccine and recombinant fowlpoxvirus-AI haemagglutinin vaccine were tested for the ability to protect chickens against multiple highly pathogenic (HP) H5 AI viruses. The vaccine and challenge viruses, or their haemagglutinin protein components, were obtained from field AI viruses of diverse backgrounds and included strains obtained from four continents, six host species, and isolated over a 38-year-period. The vaccines protected against clinical signs and death, and reduced the number of chickens shedding virus and the titre of the virus shed following a HP H5 AI virus challenge. Immunization with these vaccines should decrease AI virus shedding from the respiratory and digestive tracts of AI virus exposed chickens and reduce bird-to-bird transmission. Although most consistent reduction in respiratory shedding was afforded when vaccine was more similar to the challenge virus, the genetic drift of avian influenza virus did not interfere with general protection as has been reported for human influenza viruses.     

禽流感感染人的分子机制研究进展

禽流感病毒可以感染多种动物,包括人、猪、鸟、马、海豹、鲸和雪貂等。流感病毒在不同的宿主存在一定的屏障,但禽流感毒株能突破宿主屏障直接感染人,造成死亡。因此流感病毒的变异和病毒如何选择物种跨越物种流行的机制,对预防和控制流感的爆发是非常重要的。本文综述病毒毒力的分子生物学基础、禽流感染人的分子机制研究进展及在控制禽流感方面的研究。     

Low pathogenicity avian influenza viruses infect chicken layers by different routes of inoculation

In order to develop better control measures against avian influenza, it is necessary to understand how the virus transmits in poultry. In a previous study in which the infectivity and transmissibility of the pandemic H1N1 influenza virus was examined in different poultry species, we found that no or minimal infection occurred in chicken and turkeys intranasally (IN) inoculated with the virus. However, we demonstrated that the virus can infect laying turkey hens by the intracloacal (IC) and intraoviduct (IO) routes, possibly explaining the drops in egg production observed in turkey breeder farms affected by the virus. Such novel routes of exposure have not been previously examined in chickens and could also explain outbreaks of low pathogenicity avian influenza (LPAI) that cause a decrease in egg production in chicken layers and breeders. In the present study, 46-wk-old specific-pathogen-free chicken layers were infected by the IN, IC, or IO routes with one of two LPAI viruses: a poultry origin virus, A/chicken/CA/1255/02 (H6N2), and a live bird market isolate, A/chicken/NJ/12220/97 (H9N2). Only hens IN inoculated with the H6N2 virus presented mild clinical signs consisting of depression and anorexia. However, a decrease in number of eggs laid was observed in all virus-inoculated groups when compared to control hens. Evidence of infection was found in all chickens inoculated with the H6N2 virus by any of the three routes and the virus transmitted to contact hens. On the other hand, only one or two hens from each of the groups inoculated with the H9N2 virus shed detectable levels of virus, or seroconverted and did not transmit the virus to contacts, regardless of the route of inoculation. In conclusion, LPAI viruses can also infect chickens through other routes besides the IN route, which is considered the natural route of exposure. However, as seen with the H9N2 virus, the infectivity of the virus did not increase when given by these alternate routes.     

Experimental infection of chickens, ducks and quails with the highly pathogenic H5N1 avian influenza virus

Highly pathogenic avian influenza viruses (HPAIV) of the H5N1 subtype have spread since 2003 in poultry and wild birds in Asia, Europe and Africa. In Korea, the highly pathogenic H5N1 avian influenza outbreaks took place in 2003/2004, 2006/2007 and 2008. As the 2006/2007 isolates differ phylogenetically from the 2003/2004 isolates, we assessed the clinical responses of chickens, ducks and quails to intranasal inoculation of the 2006/2007 index case virus, A/chicken/Korea/IS/06. All the chickens and quails died on 3 days and 3-6 days post-inoculation (DPI), respectively, whilst the ducks only showed signs of mild depression. The uninoculated chickens and quails placed soon after with the inoculated flock died on 5.3 and 7.5 DPI, respectively. Both oropharyngeal and cloacal swabs were taken for all three species during various time intervals after inoculation. It was found that oropharyngeal swabs showed higher viral titers than in cloacal swabs applicable to all three avian species. The chickens and quails shed the virus until they died (up to 3 to 6 days after inoculation, respectively) whilst the ducks shed the virus on 2-4 DPI. The postmortem tissues collected from the chickens and quails on day 3 and days 4-5 and from clinically normal ducks that were euthanized on day 4 contained the virus. However, the ducks had significantly lower viral titers than the chickens or quails. Thus, the three avian species varied significantly in their clinical signs, mortality, tissue virus titers, and duration of virus shedding. Our observations suggest that duck and quail farms should be monitored particularly closely for the presence of HPAIV so that further virus transmission to other avian or mammalian hosts can be prevented.     

Avian influenza: eradication from commercial poultry is still not in sight

Avian influenza viruses are highly infectious micro-organisms that primarily affect birds. Nevertheless, they have also been isolated from a number of mammals, including humans. Avian influenza virus can cause large economic losses to the poultry industry because of its high mortality. Although there are pathogenic variants with a low virulence and which generally cause only mild, if any, clinical symptoms, the subtypes H5 and H7 can mutate from a low to a highly virulent (pathogenic) virus and should be taken into consideration in eradication strategies. The primary source of infection for commercial poultry is direct and indirect contact with wild birds, with waterfowl forming a natural reservoir of the virus. Live-poultry markets, exotic birds, and ostriches also play a significant role in the epidemiology of avian influenza. The secondary transmission (i.e., between poultry farms) of avian influenza virus is attributed primarily to fomites and people. Airborne transmission is also important, and the virus can be spread by aerosol in humans. Diagnostic tests detect viral proteins and genes. Virus-specific antibodies can be traced by serological tests, with virus isolation and identification being complementary procedures. The number of outbreaks of avian influenza seems to be increasing - over the last 5 years outbreaks have been reported in Italy, Hong Kong, Chile, the Netherlands, South Korea, Vietnam, Japan, Thailand, Cambodia, Indonesia, Laos, China, Pakistan, United States of America, Canada, South Africa, and Malaysia. Moreover, a growing number of human cases of avian influenza, in some cases fatal, have paralleled the outbreaks in commercial poultry. There is great concern about the possibility that a new virus subtype with pandemic potential could emerge from these outbreaks. From the perspective of human health, it is essential to eradicate the virus from poultry; however, the large number of small-holdings with poultry, the lack of control experience and resources, and the international scale of transmission and infection make rapid control and long-term prevention of recurrence extremely difficult. In the Western world, the renewed interest in free-range housing carries a threat for future outbreaks. The growing ethical objections to the largescale culling of birds require a different approach to the eradication of avian influenza.     

禽流感病毒宿主特异性与致病性的分子基础研究进展

禽流感病毒不断重排和变异导致新型流感病毒不断出现,其中有些毒株已经获得了感染哺乳动物的能力,严重危害人类公共卫生安全。近年来,对于禽流感病毒致宿主特异性和致病性的研究取得了一定进展。病毒蛋白某些氨基酸位点的突变就能够改变病毒的宿主特异性,使病毒能够跨宿主传播。而且,病毒的RNA聚合酶、NS1非结构蛋白和几种新发现的病毒蛋白都与病毒的致病性密切相关。论文阐述了禽流感病毒宿主特异性与致病性的分子基础,为禽流感跨物种传播机制研究及防控工作提供参考。     

Potential of low pathogenicity avian influenza viruses of wild bird origin to establish experimental infections in turkeys and chickens

The potential of low pathogenicity (LP) avian influenza virus (AIV) isolates of wild bird origin to establish infection in commercial turkeys and broiler chickens was studied. Isolates, representing subtypes H5N1, H7N3, H6N2, and H3N6, were recovered in 2005 and 2006 from waterfowl and shorebirds in the Delmarva Peninsula region of the east coast of the United States. The LP AIV isolates were not pathogenic for 2-wk-old meat-type turkeys and broiler chickens. No mortality, clinical signs, or gross lesions were observed following intratracheal and conjunctival sac routes of exposures with 10(6.0) EID50 (embryo infectious dose) per bird. Isolates resulting in an established infection based on virus isolation were: A/mallard/Maryland/1159/ 2006 (H5N1) in the upper respiratory tract of turkeys; A/mallard/Delaware/418/2005 (H7N3) in the upper respiratory and intestinal tracts of turkeys and chickens; and A/shorebird-environment/Delaware/251/2005 (H3N6) in the upper respiratory and intestinal tracts of chickens. Infections were also confirmed by production of AIV-specific serum antibodies detected by hemagglutination inhibition.     

Differences in receptor specificity between Newcastle disease viruses originating from chickens and waterfowl.

We compared the receptor specificity of Newcastle disease viruses from a variety of avian species, including chickens and wild waterfowl, using hemagglutination tests with erythrocytes from different animal species. All isolates from wild waterfowl agglutinated horse erythrocytes, while the chicken isolates did not. The results showed that the receptor specificity of Newcastle disease viruses is different, depending on the avian species from which the viruses are isolated.     

Classic fowl plague--a review

Highly pathogenic avian influenza (HPAI) represents a severe form of generalized avian influenza which is characterized by a rapid and severe course of disease and a very high mortality. All poultry species are susceptible. Turkeys and chickens are most vulnerable. There are no pathognomonic symptoms or specific pathological alterations. The disease is caused by avian influenza virus strains of the subtypes H5 or H7. These viruses arise spontaneously from apathogenic progenitors by insertional mutation in the HA gene. Until recently, outbreaks of HPAI were rare events, however, they have been found to cause increasing losses over the past few years. Since 2003, a widespread occurrence of HPAI has been registered in southeast Asia, and some countries are endemically infected with HPAIV strain H5N1. In six countries this virus has also caused fatal human infections. This has sparked fears that this agent may be the progenitor of a new pandemic influenza virus. During summer 2005 the disease has slowly spread westward. Isolated outbreaks have been reported from Kazakhstan, Russia, Romania, Turkey, Croatia and Ukraine. Migratory birds have been tentatively accused for spreading the infection along their flyways.     

Isolation from turkey breeder hens of a reassortant H1N2 influenza virus with swine, human, and avian lineage genes

Type A influenza viruses can infect a wide range of birds and mammals, but influenza in a particular species is usually considered to be species specific. However, infection of turkeys with swine H1N1 viruses has been documented on several occasions. This report documents the isolation of an H1N2 influenza virus from a turkey breeder flock with a sudden drop in egg production. Sequence analysis of the virus showed that it was a complex reassortant virus with a mix of swine-, human-, and avian-origin influenza genes. A swine influenza virus with a similar gene complement was recently reported from pigs in Indiana. Isolation and identification of the virus required the use of nonconventional diagnostic procedures. The virus was isolated in embryonated chicken eggs by the yolk sac route of inoculation rather than by the typical chorioallantoic sac route. Interpretation of hemagglutination-inhibition test results required the use of turkey rather than chicken red blood cells, and identification of the neuraminidase subtype required the use of alternative reference sera in the neuraminidase-inhibition test. This report provides additional evidence that influenza viruses can cross species and cause a disease outbreak, and diagnosticians must be aware that the variability of influenza viruses can complicate the isolation and characterization of new isolates.