RESUMEN
After an outbreak of pandemic influenza A/H1N1 (pH1N1) virus, we had previously reported the emergence of a recombinant canine influenza virus (CIV) between the pH1N1 virus and the classic H3N2 CIV. Our ongoing routine surveillance isolated another reassortant H3N2 CIV carrying the matrix gene of the pH1N1 virus from 2012. The infection dynamics of this H3N2 CIV variant (CIV/H3N2mv) were investigated in dogs and ferrets via experimental infection and transmission. The CIV/H3N2mv-infected dogs and ferrets produced typical symptoms of respiratory disease, virus shedding, seroconversion, and direct-contact transmissions. Although indirect exposure was not presented for ferrets, CIV/H3N2mv presented higher viral replication in MDCK cells and more efficient transmission was observed in ferrets compared to classic CIV H3N2. This study demonstrates the effect of reassortment of the M gene of pH1N1 in CIV H3N2.
Asunto(s)
Enfermedades de los Perros/virología , Hurones/virología , Subtipo H1N1 del Virus de la Influenza A/genética , Infecciones por Orthomyxoviridae/veterinaria , Pandemias/veterinaria , Animales , Secuencia de Bases , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/transmisión , Perros/virología , Genes Virales/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Células de Riñón Canino Madin Darby/virología , Datos de Secuencia Molecular , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/genética , Infecciones por Orthomyxoviridae/transmisión , Pandemias/estadística & datos numéricos , Recombinación Genética/genética , Proteínas de la Matriz Viral/genéticaRESUMEN
Recently, novel H7N9 influenza viruses have caused an unprecedented outbreak in humans. Pigs are an important intermediate host for influenza; thus, we assessed the replication ability of three human H7N9 viruses (A/Anhui/1/2013, A/Shanghai/1/2013, A/Shanghai/2/2013) in swine tissue explants. All viruses tested replicated efficiently in explants from tracheas and bronchi, with limited replication in alveolar cells. Swine respiratory tissue explants can serve as an efficient model for screening replication potential of newly emerging H7N9 viruses.
Asunto(s)
Bronquios/virología , Subtipo H7N9 del Virus de la Influenza A/patogenicidad , Infecciones por Orthomyxoviridae/virología , Alveolos Pulmonares/virología , Tráquea/virología , Animales , Bronquios/metabolismo , Humanos , Técnicas para Inmunoenzimas , Infecciones por Orthomyxoviridae/metabolismo , Alveolos Pulmonares/metabolismo , Porcinos , Porcinos Enanos , Técnicas de Cultivo de Tejidos , Tráquea/metabolismoRESUMEN
After emerging in Egypt in 2006, highly pathogenic avian influenza H5N1 viruses continued to cause outbreaks in Egyptian poultry and sporadic human infections. The strategy used by Egyptian authorities relied on vaccinating poultry, depopulating infected areas, and increasing awareness and biosecurity levels. Despite those efforts, H5N1 became endemic, and vaccine-escape variants are thought to have emerged even though commercial poultry vaccines were protective in laboratory settings. We studied the cross-reactivity of 6 commercially available H5 poultry vaccines against recent H5N1 Egyptian isolates in a field setting in Egypt. Only one vaccine based on an Egyptian H5N1 virus induced high cross-reactive antibody titers. Our results may be explained by the fact that the seed viruses in these vaccines are genetically distinct from H5N1 viruses currently circulating in Egypt. In light of our findings, we recommend that the H5N1 prevention and control strategy in Egypt be updated and reinforced. Special consideration should be given to the vaccination strategy, and the use of vaccines based on currently circulating viruses is advisable.
Asunto(s)
Anticuerpos Antivirales/inmunología , Pollos , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Aviar/prevención & control , Animales , Egipto/epidemiología , Vacunas contra la Influenza/clasificación , Gripe Aviar/epidemiologíaRESUMEN
In the past 4 years, incidences of endemic or epidemic respiratory diseases associated with canine influenza H3N2 virus in Asian dogs have been reported in countries such as South Korea and China. Canine species were considered to be the new natural hosts for this virus. However, at the beginning of 2010, influenza-like respiratory signs, such as dyspnoea, were also observed among cats as well as in dogs in an animal shelter located in Seoul, South Korea. The affected cats showed 100â% morbidity and 40â% mortality. We were able to isolate a virus from a lung specimen of a dead cat, which had suffered from the respiratory disease, in embryonated-chicken eggs. The eight viral genes isolated were almost identical to those of the canine influenza H3N2 virus, suggesting interspecies transmission of canine influenza H3N2 virus to the cat. Moreover, three domestic cats infected with intranasal canine/Korea/GCVP01/07 (H3N2) all showed elevated rectal temperatures, nasal virus shedding and severe pulmonary lesions, such as suppurative bronchopneumonia. Our study shows, for the first time, that cats are susceptible to canine influenza H3N2 infection, suggesting that cats may play an intermediate host role in transmitting the H3N2 virus among feline and canine species, which could lead to the endemic establishment of the virus in companion animals. Such a scenario raises a public health concern, as the possibility of the emergence of new recombinant feline or canine influenza viruses in companion animals with the potential to act as a zoonotic infection cannot be excluded.
Asunto(s)
Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/virología , Enfermedades de los Perros/transmisión , Enfermedades de los Perros/virología , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Infecciones por Orthomyxoviridae/veterinaria , Animales , Temperatura Corporal , Enfermedades de los Gatos/mortalidad , Enfermedades de los Gatos/patología , Gatos , Análisis por Conglomerados , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/patología , Perros , Heces/virología , Subtipo H3N2 del Virus de la Influenza A/clasificación , Subtipo H3N2 del Virus de la Influenza A/genética , Pulmón/virología , Datos de Secuencia Molecular , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/virología , Filogenia , ARN Viral/genética , República de Corea/epidemiología , Análisis de Secuencia de ADN , Esparcimiento de VirusRESUMEN
Multiple reassortment events between different subtypes of endemic avian influenza viruses have increased the genomic diversity of influenza viruses circulating in poultry in southern China. Gene exchange from the natural gene pool to poultry has contributed to this increase in genetic diversity. However, the role of domestic ducks as an interface between the natural gene pool and terrestrial poultry in the influenza virus ecosystem has not been fully characterized. Here we phylogenetically and antigenically analyzed 170 H6 viruses isolated from domestic ducks from 2000 to 2005 in southern China, which contains the largest population of domestic ducks in the world. Three distinct hemagglutinin lineages were identified. Group I contained the majority of isolates with a single internal gene complex and was endemic in domestic ducks in Guangdong from the late 1990s onward. Group II was derived from reassortment events in which the surface genes of group I viruses were replaced with novel H6 and N2 genes. Group III represented H6 viruses that undergo frequent reassortment with multiple virus subtypes from the natural gene pool. Surprisingly, H6 viruses endemic in domestic ducks and terrestrial poultry seldom reassort, but gene exchanges between viruses from domestic ducks and migratory ducks occurred throughout the surveillance period. These findings suggest that domestic ducks in southern China mediate the interaction of viruses between different gene pools and facilitate the generation of novel influenza virus variants circulating in poultry.
Asunto(s)
Patos/virología , Virus de la Influenza A/genética , Gripe Aviar/virología , Virus Reordenados/genética , Animales , Antígenos Virales/clasificación , Antígenos Virales/genética , China/epidemiología , Reservorios de Enfermedades/virología , Patos/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/clasificación , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Virus de la Influenza A/clasificación , Virus de la Influenza A/patogenicidad , Gripe Aviar/epidemiología , Gripe Humana , Filogenia , Virus Reordenados/clasificación , Virus Reordenados/aislamiento & purificación , Proteínas Virales/clasificación , Proteínas Virales/genética , Zoonosis/virologíaRESUMEN
When primary immunity is boosted not by the homologous but by a crossreacting vaccine, the newly formed antibodies react better with the primary antigen than with the antigen actually eliciting the response. This phenomenon bears the name of Original Antigenic Sin (1). It is shown that the number of antibody molecules produced against the original and the vaccinating antigen is the same; that each of these molecules is capable of reacting with both antigens; that the activity of an antiserum can be completely absorbed with either antigen; that both residual and adsorbed-dissociated fractions of antibody exhibit the same relative affinities towards the two antigens as did the native serum; that, unlike standard primary and secondary responses, the population of antibody molecules characterizing the Original Antigenic Sin is homogeneous; that each molecule has a lower equilibrium constant (i.e. higher avidity) against the original antigen than against the antigen stimulating the present response; and that all equilibrium constants are typical of secondary antibody. It is concluded that the Original Antigenic Sin is a partial anamnestic response, a related antigen stimulating that sector only of the originally primed cells which is destined to produce cross-reacting antibody. A hypothesis is developed according to which the basic difference between primary and secondary reactivity rests on the presence of a trapping mechanism that allows anamnestic production of antibody against lower doses of the homologous antigen. Such a mechanism is capable of cross-trapping related antigens, thus preventing a standard primary response and allowing manifestations of Original Antigenic Sin.
Asunto(s)
Formación de Anticuerpos , Antígenos , Vacunas contra la Influenza , Gripe Humana/inmunología , Niño , Preescolar , Estudios de Seguimiento , Pruebas de Hemaglutinación , HumanosRESUMEN
Experiments in rabbits were designed to test the two unproven assumptions of the hypothesis proposed in the companion paper (1): that Original Antigenic Sin is fundamentally a restricted anamnestic response, and that there exists a trapping mechanism capable of deflecting antigen from one kind of cell and guiding it to another. It is shown that whole-body X-irradiation, sufficient to abolish primary but not secondary production of antibodies, leaves all manifestations of the Original Antigenic Sin untouched. This proves the first assumption. Primary immune animals challenged with very large doses of a related antigen produce an immediate response of cross-reactive antibodies, followed by a standard primary response to the challenging antigen. When boosted with an appropriate mixture of both antigens, the response is of standard secondary type to the homologous antigen, followed by a standard primary response to the crossreacting antigen. When animals are primarily vaccinated with a mixture of two related antigens, small booster doses of either will stimulate a standard secondary response only. When such animals are given very large booster doses of either antigen, the response is a compound of a homologous secondary and of an Original Antigenic Sin-type against the related antigen. Each of these findings demonstrates a corollary of the second assumption. The results are discussed in terms of the limitations they impose on theories concerned with the production of antibodies.
Asunto(s)
Formación de Anticuerpos , Antígenos/farmacología , Vacunas contra la Influenza/farmacología , Infecciones por Orthomyxoviridae/inmunología , Animales , Conejos , Efectos de la RadiaciónRESUMEN
Antigenic variants of A/PR/8/34 [HON1] influenza virus were selected after a single passage of the parent virus in embryonated chicken eggs in the presence of monoclonal antibodies to this virus. The monoclonal antibodies were produced by a hybridoma and were specific for an antigenic determinant on the HA molecule of the parent virus. Seven antigenic variants were analyzed with 95 monoclonal anti-HA antibodies prepared in vitro in the splenic fragment culture system. Three subgroups of antigenic variants were distinguished. The antigenic changes were primarily recognized by monoclonal antibodies to the strain- specific determinants of the parental hemagglutinin (HA) molecule. Monoclonal antibodies to HA determinants shared (in an identical or cross-reactive form) by parental virus and more than three heterologous viruses of the HON1 and H1N1 subtypes were unable to recognize the antigenic change on the variants. Similarly, heterogeneous antibody preparations could not differentiate between parental and variant viruses. The results are compatible with the idea that the HA of PR8 has available a large repertoire of antigenic modifications that may result from single amino acid substitutions, and that antigenic changes can occur in the strain- specific determinants on the HA molecule in the absence of concomitant changes in the cross-reactive HA determinants. The findings suggest that antigenic drift, in order to be epidemiologically significant, probably requires a series of amino acid substitutions in, or close to, the antigenic area on the HA molecule.
Asunto(s)
Antígenos Virales/análisis , Virus de la Influenza A/inmunología , Anticuerpos Antivirales , Reacciones Antígeno-Anticuerpo , Antígenos de Superficie/análisis , Células Clonales/inmunología , Técnicas InmunológicasRESUMEN
Antisera to the type-specific internal influenza virus matrix (M) protein of a type A influenza virus were produced in goats. In the presence of complement, anti-M serum was cytotoxic for target cells which were infected with a variety of serologically distinct type A influenza viruses, but did not react with type B influenza virus-infected cells. Absorption experiments indicated that anti-M serum detected a common antigen(s) on the surface of type A-infected cells. This serological cross-reactivity parallels the cross-reactivity observed for the cytotoxic T-cell response to type A viruses.
Asunto(s)
Anticuerpos Antivirales , Antígenos Virales/análisis , Membrana Celular/inmunología , Virus de la Influenza A/inmunología , Proteínas Virales/inmunología , Línea Celular , Pruebas Inmunológicas de Citotoxicidad , EpítoposRESUMEN
Monoclonal antibody to type-A influenza virus matrix (M)-protein was used to quantitate the appearance of M-protein on abortively infected P815 cells. After 16 h of infection with different type-A viruses, only a low amount of M-protein appears on the surface of infected cells (approximately 10(3) site/cell) in contrast to approximately 10(5) hemagglutinin molecules on each cell surface. However, virus replication is required for M-protein appearance. Analysis of solubilized membranes purified from 16-h-infected cells shows approximately 10(4) M-protein molecule/cell in the plasma membrane, a content that is consistent with the observed low surface expression, and that indicates that most of the M-protein is localized internally. We found no evidence that cross-reactive cytotoxic T cells could recognize M-protein; neither monoclonal antibody or hyperimmune anti-M-protein antiserum could inhibit T cell killing, either alone or in combination with monoclonal anti-H-2 antibody. Taken together, the low level of M-protein appearance and lack of T cell blocking by anti-M-protein antibody leaves doubt that M-protein is the antigen recognized by cross-reactive cytotoxic T cells.
Asunto(s)
Antígenos Virales , Citotoxicidad Inmunológica , Infecciones por Orthomyxoviridae/inmunología , Linfocitos T/inmunología , Animales , Anticuerpos Antivirales , Especificidad de Anticuerpos , Células Cultivadas , Proteínas del Sistema Complemento/metabolismo , Proteínas de la Membrana/inmunología , Ratones , Orthomyxoviridae/inmunología , Proteínas Virales/inmunología , Replicación ViralRESUMEN
In our earlier studies, we showed that an escape mutant of mouse-adapted H9N2 influenza virus carrying a T198N amino acid change in heamagglutinin (HA) has a lowered virulence for mice. The readaptation of this mutant to mice was associated with N198S or N198D reverse mutations. In this study, single-gene reassortants having HA gene of the wild-type virus, its low-virulence escape mutant, or a readapted variant were generated by site-specific mutagenesis and assayed for virulence. The results showed that antibody-selected mutations in the HA of H9 influenza virus can decrease mortality and virus accumulation in mouse lungs, though not in nasal turbinates, and the effect may be compensated by reverse mutations in the course of passaging.
Asunto(s)
Hemaglutininas Virales/genética , Subtipo H9N2 del Virus de la Influenza A/fisiología , Subtipo H9N2 del Virus de la Influenza A/patogenicidad , Gripe Humana/virología , Mutación , Adaptación Fisiológica , Sustitución de Aminoácidos , Animales , Línea Celular , Hemaglutininas Virales/metabolismo , Humanos , Subtipo H9N2 del Virus de la Influenza A/clasificación , Subtipo H9N2 del Virus de la Influenza A/genética , Gripe Humana/patología , Pulmón/patología , Pulmón/virología , Ratones , Mutagénesis Sitio-Dirigida , VirulenciaRESUMEN
A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 (refs 2-4) and subsequent avian outbreaks in 2001 and 2002 (refs 5, 6). These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003-04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.
Asunto(s)
Evolución Molecular , Gripe Humana/epidemiología , Gripe Humana/virología , Orthomyxoviridae/genética , Orthomyxoviridae/patogenicidad , Animales , Aves/virología , Asia Oriental/epidemiología , Genes Virales/genética , Genotipo , Humanos , Gripe Humana/transmisión , Datos de Secuencia Molecular , Mutación/genética , Orthomyxoviridae/aislamiento & purificación , Filogenia , Virus Reordenados/genética , Virus Reordenados/aislamiento & purificación , Virus Reordenados/patogenicidad , Factores de TiempoRESUMEN
The transmission of highly pathogenic avian influenza H5N1 virus to Southeast Asian countries triggered the first major outbreak and transmission wave in late 2003, accelerating the pandemic threat to the world. Due to the lack of influenza surveillance prior to these outbreaks, the genetic diversity and the transmission pathways of H5N1 viruses from this period remain undefined. To determine the possible source of the wave 1 H5N1 viruses, we recently conducted further sequencing and analysis of samples collected in live-poultry markets from Guangdong, Hunan, and Yunnan in southern China from 2001 to 2004. Phylogenetic analysis of the hemagglutinin and neuraminidase genes of 73 H5N1 isolates from this period revealed a greater genetic diversity in southern China than previously reported. Moreover, results show that eight viruses isolated from Yunnan in 2002 and 2003 were most closely related to the clade 1 virus sublineage from Vietnam, Thailand, and Malaysia, while two viruses from Hunan in 2002 and 2003 were most closely related to viruses from Indonesia (clade 2.1). Further phylogenetic analyses of the six internal genes showed that all 10 of those viruses maintained similar phylogenetic relationships as the surface genes. The 10 progenitor viruses were genotype Z and shared high similarity (>/=99%) with their corresponding descendant viruses in most gene segments. These results suggest a direct transmission link for H5N1 viruses between Yunnan and Vietnam and also between Hunan and Indonesia during 2002 and 2003. Poultry trade may be responsible for virus introduction to Vietnam, while the transmission route from Hunan to Indonesia remains unclear.
Asunto(s)
Subtipo H5N1 del Virus de la Influenza A/clasificación , Subtipo H5N1 del Virus de la Influenza A/genética , Gripe Aviar/virología , Enfermedades de las Aves de Corral/virología , ARN Viral/genética , Animales , China/epidemiología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/epidemiología , Epidemiología Molecular , Datos de Secuencia Molecular , Neuraminidasa/genética , Filogenia , Aves de Corral , Enfermedades de las Aves de Corral/epidemiología , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Proteínas Virales/genéticaRESUMEN
The influenza virus hemagglutinin (HA) is a well-characterized integral membrane glycoprotein composed of three identical subunits. We have analyzed the formation of mixed trimers in cells expressing two different HA gene products. The results show efficient and essentially random assembly of functional hybrid trimers provided that the HAs are from the same HA subtype. Trimerization is thus a posttranslational event, and subunits are recruited randomly from a common pool of monomers in the endoplasmic reticulum. Mixed trimers were not observed between HAs derived from different subtypes, indicating that the trimerization event is sequence specific. Mixed trimers containing mutant subunits were, moreover, used to establish that the acid-induced conformational change involved in the membrane fusion activity of HA is a highly cooperative event.
Asunto(s)
Hemaglutininas Virales/metabolismo , Virus de la Influenza A/metabolismo , Procesamiento Proteico-Postraduccional , Animales , Fusión Celular/efectos de los fármacos , Línea Celular , Electroforesis en Gel de Poliacrilamida , Técnica del Anticuerpo Fluorescente , Glicoproteínas Hemaglutininas del Virus de la Influenza , Hemaglutininas Virales/genética , Concentración de Iones de Hidrógeno , Inmunoensayo , Virus de la Influenza A/genética , Sustancias Macromoleculares , Conformación ProteicaRESUMEN
The hemagglutinin (HA) of influenza virus is a homotrimeric integral membrane glycoprotein. It is cotranslationally inserted into the endoplasmic reticulum as a precursor called HA0 and transported to the cell surface via the Golgi complex. We have, in this study, investigated the kinetics and cellular location of the assembly reaction that results in HA0 trimerization. Three independent criteria were used for determining the formation of quaternary structure: the appearance of an epitope recognized by trimer-specific monoclonal antibodies; the acquisition of trypsin resistance, a characteristic of trimers; and the formation of stable complexes which cosedimented with the mature HA0 trimer (9S20,w) in sucrose gradients containing Triton X-100. The results showed that oligomer formation is a posttranslational event, occurring with a half time of approximately 7.5 min after completion of synthesis. Assembly occurs in the endoplasmic reticulum, followed almost immediately by transport to the Golgi complex. A stabilization event in trimer structure occurs when HA0 leaves the Golgi complex or reaches the plasma membrane. Approximately 10% of the newly synthesized HA0 formed aberrant trimers which were not transported from the endoplasmic reticulum to the Golgi complex or the plasma membrane. Taken together the results suggested that formation of correctly folded quaternary structure constitutes a key event regulating the transport of the protein out of the endoplasmic reticulum. Further changes in subunit interactions occur as the trimers move along the secretory pathway.
Asunto(s)
Hemaglutininas Virales/metabolismo , Virus de la Influenza A/análisis , Animales , Transporte Biológico , Línea Celular , Membrana Celular/metabolismo , Chlorocebus aethiops , Epítopos/inmunología , Fibroblastos/metabolismo , Aparato de Golgi/metabolismo , Glicoproteínas Hemaglutininas del Virus de la Influenza , Hemaglutininas Virales/inmunología , Riñón , Modelos Moleculares , Conformación Proteica , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , Tripsina/farmacologíaRESUMEN
The A/Hong Kong/1/68 (H3N2) influenza virus which has not been isolated from man for several years, was recently isolated from pigs in Hong Kong. Influenza viruses similar to A/Victoria/3/75, which are currently circulating in man, were also isolated from pigs. Both above-mentioned viruses could be transmitted readily from pig to pig in experimental studies. The isolation of influenza viruses similar to A/Hong Kong/68 from pigs in 1976 suggests that pigs may serve as a potential reservoir for future human pandemics as well as a possible source of genetic information for recombination between human and porcine strains of influenza virus.
Asunto(s)
Virus de la Influenza A/aislamiento & purificación , Infecciones por Orthomyxoviridae/transmisión , Porcinos/microbiología , Animales , Reservorios de EnfermedadesRESUMEN
Influenza A viruses (subtype H1N1), recently isolated from turkeys in different areas of the United States, were determined to be closely related to strains typically associated with pigs. This conclusion was based on comparisons of H1N1 isolates from pigs, humans, ducks, and turkeys with polyclonal and monoclonal antibodies, RNA-RNA competitive hybridization, and replication studies. One of the H1N1 isolates from turkeys caused influenza in a laboratory technician, who displayed fever, respiratory illness, virus shedding, and seroconversion. These results suggest that turkeys as well as pigs are involved in the maintenance of these viruses and their transmission to humans.
Asunto(s)
Virus de la Influenza A/aislamiento & purificación , Infecciones por Orthomyxoviridae/transmisión , Pavos/microbiología , Animales , Anticuerpos Monoclonales/inmunología , Antígenos Virales/inmunología , Patos/microbiología , Hurones/inmunología , Humanos , Virus de la Influenza A/inmunología , Enfermedades de las Aves de Corral/microbiología , ARN Viral/metabolismo , Porcinos/microbiologíaRESUMEN
An influenza A reassortant virus that contained the hemagglutinin and neuraminidase genes of a virulent human virus, A/Udorn/72 (H3N2), and the six other influenza A virus genome segments from an avirulent avian virus, A/Mallard/New York/6750/78 (H2N2), was evaluated for its level of replication is squirrel monkeys and hamsters. In monkeys, the reassortant virus was as attenuated and as restricted in its level of replication in the upper and lower respiratory tract as its avian influenza virus parent. Nonetheless, infection with the reassortant induced significant resistant to challenge with virulent human influenza virus. In hamsters, the reassortant virus replicated to a level intermediate between that of its parents. These findings suggest that the nonsurface antigen genes of the avian parental virus are the primary determinants of restriction of replication of the reassortant virus in monkeys. Attenuation of the reassortant virus for primates is achieved by inefficient functioning of the avian influenza genes in primate cells, while antigenic specificity of the human influenza virus is provided by the neuraminidase and hemagglutinin genes derived from the human virus. This approach could lead to the development of a live influenza A virus vaccine that is attenuated for man if the avian influenza genes are similarly restricted in human cells.
Asunto(s)
Virus de la Influenza A/genética , Vacunas contra la Influenza/inmunología , Animales , Antígenos de Superficie/genética , Cricetinae , Epítopos/genética , Epítopos/inmunología , Hemaglutininas/genética , Hemaglutininas/inmunología , Neuraminidasa/genética , Neuraminidasa/inmunología , Saimiri , Vacunas Atenuadas/inmunologíaRESUMEN
More than 400 harbor seals, most of them immature, died along the New England coast between December 1979 and October 1980 of acute pneumonia associated with influenza virus, A/Seal/Mass/1/180 (H7N7). The virus has avian characteristics, replicates principally in mammals, and causes mild respiratory disease in experimentally infected seals. Concurrent infection with a previously undescribed mycoplasma or adverse environmental conditions may have triggered the epizootic. The similarities between this epizootic and other seal mortalities in the past suggest that these events may be linked by common biological and environmental factors.
Asunto(s)
Caniformia/microbiología , Brotes de Enfermedades/veterinaria , Infecciones por Orthomyxoviridae/veterinaria , Neumonía/veterinaria , Phocidae/microbiología , Animales , Virus de la Influenza A/aislamiento & purificaciónRESUMEN
The highly pathogenic Asian H5N1 influenza virus that was first detected in Guangdong in the People's Republic of China (China) in 1996 is unique in having spread to humans and other mammalian species. To date, this virus has not consistently transmitted between any mammalian species but the continued spread and evolution of these viruses in domestic poultry across Eurasia presents a continuing pandemic threat. These viruses have caused devastation in domestic poultry and have killed over 60% of infected humans. The H5N1 viruses are unique in having evolved into multiple clades and subclades by reassortment with other influenza viruses in the epicentre of southern China, and accumulation of point mutations has resulted in antigenic differences between the clades. Three waves of spread have occurred, wave one to East Asia and Southeast Asia, wave two through Qinghai Lake, China, to Europe, India and Africa, and wave three to Southeast Asia again. This paper deals with the molecular epidemiology of the evolution of the multiplicity of H5N1 clades. The continuing evolution of these H5N1 viruses and the possible establishment of secondary epicentres in Indonesia, Egypt and Nigeria present a continuing threat to poultry and people globally.