Little evidence for genetic susceptibility to influenza A (H5N1) from family clustering data.
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ABSTRACT:
SUBMITTER: Pitzer VE
PROVIDER: S-EPMC2878232 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Since 2005, the Qinghai-like lineage of the highly pathogenic avian influenza A virus H5N1 has rapidly spread westward to Europe, the Middle East and Africa, reaching a dominant level at a global scale in 2006. METHODS: Based on a combination of genetic sequence data and H5N1 outbreak information from 2005 to 2011, we use an interdisciplinary approach to improve our understanding of the transmission pattern of this particular clade 2.2, and present cartography of global spatiotemporal transmission footprints with genetic characteristics. RESULTS: Four major viral transmission routes were derived with three sources- Russia, Mongolia, and the Middle East (Kuwait and Saudi Arabia)-in the three consecutive years 2005, 2006 and 2007. With spatiotemporal transmission along each route, genetic distances to isolate A/goose/Guangdong/1996 are becoming significantly larger, leading to a more challenging situation in certain regions like Korea, India, France, Germany, Nigeria and Sudan. Europe and India have had at least two incursions along multiple routes, causing a mixed virus situation. In addition, spatiotemporal distribution along the routes showed that 2007/2008 was a temporal separation point for the infection of different host species; specifically, wild birds were the main host in 2005-2007/2008 and poultry was responsible for the genetic mutation in 2009-2011. "Global-to-local" and "high-to-low latitude" transmission footprints have been observed. CONCLUSIONS: Our results suggest that both wild birds and poultry play important roles in the transmission of the H5N1 virus clade, but with different spatial, temporal, and genetic dominance. These characteristics necessitate that special attention be paid to countries along the transmission routes.
| S-EPMC4059878 | biostudies-other
Project description:Genetic reassortment of H5N1 highly pathogenic avian influenza viruses (HPAI) with currently circulating human influenza A strains is one possibility that could lead to efficient human-to-human transmissibility. Domestic pigs which are susceptible to infection with both human and avian influenza A viruses are one of the natural hosts where such reassortment events could occur. Virological, histological and serological features of H5N1 virus infection in pigs were characterized in this study. Two- to three-week-old domestic piglets were intranasally inoculated with 10(6) EID(50) of A/Vietnam/1203/04 (VN/04), A/chicken/Indonesia/7/03 (Ck/Indo/03), A/Whooper swan/Mongolia/244/05 (WS/Mong/05), and A/Muscovy duck/Vietnam/ 209/05 (MDk/VN/05) viruses. Swine H3N2 and H1N1 viruses were studied as a positive control for swine influenza virus infection. The pathogenicity of the H5N1 HPAI viruses was also characterized in mouse and ferret animal models. Intranasal inoculation of pigs with H5N1 viruses or consumption of infected chicken meat did not result in severe disease. Mild weight loss was seen in pigs inoculated with WS/Mong/05, Ck/Indo/03 H5N1 and H1N1 swine influenza viruses. WS/Mong/05, Ck/Indo/03 and VN/04 viruses were detected in nasal swabs of inoculated pigs mainly on days 1 and 3. Titers of H5N1 viruses in nasal swabs were remarkably lower compared with those of swine influenza viruses. Replication of all four H5N1 viruses in pigs was restricted to the respiratory tract, mainly to the lungs. Titers of H5N1 viruses in the lungs were lower than those of swine viruses. WS/Mong/05 virus was isolated from trachea and tonsils, and MDk/VN/05 virus was isolated from nasal turbinate of infected pigs. Histological examination revealed mild to moderate bronchiolitis and multifocal alveolitis in the lungs of pigs infected with H5N1 viruses, while infection with swine influenza viruses resulted in severe tracheobronchitis and bronchointerstitial pneumonia. Pigs had low susceptibility to infection with H5N1 HPAI viruses. Inoculation of pigs with H5N1 viruses resulted in asymptomatic to mild symptomatic infection restricted to the respiratory tract and tonsils in contrast to mouse and ferrets animal models, where some of the viruses studied were highly pathogenic and replicated systemically.
| S-EPMC2438613 | biostudies-literature
Project description:In January and November 2008, outbreaks of avian influenza have been reported in 4 provinces of Thailand. Eight Influenza A H5N1 viruses were recovered from these 2008 AI outbreaks and comprehensively characterized and analyzed for nucleotide identity, genetic relatedness, virulence determinants, and possible sites of reassortment. The results show that the 2008 H5N1 viruses displayed genetic drift characteristics (less than 3% genetic differences), as commonly found in influenza A viruses. Based on phylogenetic analysis, clade 1 viruses in Thailand were divided into 3 distinct branches (subclades 1, 1.1 and 1.2). Six out of 8 H5N1 isolates have been identified as reassorted H5N1 viruses, while other isolates belong to an original H5N1 clade. These viruses have undergone inter-lineage reassortment between subclades 1.1 and 1.2 and thus represent new reassorted 2008 H5N1 viruses. The reassorted viruses have acquired gene segments from H5N1, subclade 1.1 (PA, HA, NP and M) and subclade 1.2 (PB2, PB1, NA and NS) in Thailand. Bootscan analysis of concatenated whole genome sequences of the 2008 H5N1 viruses supported the reassortment sites between subclade 1.1 and 1.2 viruses. Based on estimating of the time of the most recent common ancestors of the 2008 H5N1 viruses, the potential point of genetic reassortment of the viruses could be traced back to 2006. Genetic analysis of the 2008 H5N1 viruses has shown that most virulence determinants in all 8 genes of the viruses have remained unchanged. In summary, two predominant H5N1 lineages were circulating in 2008. The original CUK2-like lineage mainly circulated in central Thailand and the reassorted lineage (subclades 1.1 and 1.2) predominantly circulated in lower-north Thailand. To prevent new reassortment, emphasis should be put on prevention of H5N1 viruses circulating in high risk areas. In addition, surveillance and whole genome sequencing of H5N1 viruses should be routinely performed for monitoring the genetic drift of the virus and new reassorted strains, especially in light of potential reassortment between avian and mammalian H5N1 viruses.
| S-EPMC2949837 | biostudies-literature
Project description:Migratory birds have been implicated in the long-range spread of highly pathogenic avian influenza (HPAI) A virus (H5N1) from Asia to Europe and Africa. Although sampling of healthy wild birds representing a large number of species has not identified possible carriers of influenza virus (H5N1) into Europe, surveillance of dead and sick birds has demonstrated mute (Cygnus olor) and whooper (C. cygnus) swans as potential sentinels. Because of concerns that migratory birds could spread H5N1 subtype to the Western Hemisphere and lead to its establishment within free-living avian populations, experimental studies have addressed the susceptibility of several indigenous North American duck and gull species. We examined the susceptibility of Canada geese (Branta canadensis) to HPAI virus (H5N1). Large populations of this species can be found in periagricultural and periurban settings and thus may be of potential epidemiologic importance if H5N1 subtype were to establish itself in North American wild bird populations.
| S-EPMC2876756 | biostudies-literature
Project description:The complete genome sequences of two isolates A/chicken/Egypt/CL6/07 (CL6/07) and A/duck/Egypt/D2br10/07 (D2br10/07) of highly pathogenic avian influenza virus (HPAI) H5N1 isolated at the beginning of 2007 outbreak in Egypt were determined and compared with all Egyptian HPAI H5N1 sequences available in the GenBank. Sequence analysis utilizing the RNA from the original tissue homogenate showed amino acid substitutions in seven of the viral segments in both samples. Interestingly, these changes were different between the CL6/07 and D2br10/07 when compared to other Egyptian isolates. Moreover, phylogenetic analysis showed independent sub-clustering of the two viruses within the Egyptian sequences signifying a possible differential adaptation in the two hosts. Further, pre-amplification analysis of H5N1 might be necessary for accurate data interpretation and identification of distinct factor(s) influencing the evolution of the virus in different poultry species.
| S-EPMC3112484 | biostudies-literature
Project description:Selection for resource conservation can shape the coding sequences of organisms living in nutrient-limited environments. Recently, it was proposed that selection for resource conservation, specifically for nitrogen and carbon content, has also shaped the structure of the standard genetic code, such that the missense mutations the code allows tend to cause small increases in the number of nitrogen and carbon atoms in amino acids. Moreover, it was proposed that this optimization is not confounded by known optimizations of the standard genetic code, such as for polar requirement or hydropathy. We challenge these claims. We show the proposed optimization for nitrogen conservation is highly sensitive to choice of null model and the proposed optimization for carbon conservation is confounded by the known conservative nature of the standard genetic code with respect to the molecular volume of amino acids. There is therefore little evidence the standard genetic code is optimized for resource conservation. We discuss our findings in the context of null models of the standard genetic code.
| S-EPMC8557452 | biostudies-literature
Project description:The direct precursors of the A/Goose/Guangdong/1/1996 (GS/GD) virus lineage and its reassortants have been established geographically and ecologically. To investigate the variation and evolutionary dynamics of H5N1 viruses, whole-genome viral sequences (n?=?164) were retrieved from the NCBI Influenza Virus Resource. Here, we present phylogenetic evidence for intrasubtype reassortments among H5N1 viruses isolated from China during 1996-2012. On the basis of phylogenetic analysis, we identified four major groups and further classified the reassortant viruses into three subgroups. Putative mosaic structures were mostly found in the viral ribonucleoprotein (vRNP) complexes and 91.0% (10/11) mosaics were obtained from terrestrial birds. Sequence variability and selection pressure analyses revealed that both surface glycoproteins (HA and NA) and nonstructural protein 1 (NS1) have higher dN/dS ratio and variability than other internal proteins. Furthermore, we detected 47 positively selected sites in genomic segments with the exception of PB2 and M1 genes. Hemagglutinin (HA) and neuraminidase (NA) are considered highly variable due to host immune pressure, however, it is not known what drives NS1 variability. Therefore, we performed a thorough analysis of the genetic variation and selective pressure of NS1 protein (462 available NS1 sequences). We found that most of positively selected sites and variable amino acids were located in the C-terminal effector domain (ED) of NS1. In addition, we focused on the NS1-RNA and NS1-protein interactions that were involved in viral replication mechanisms and host immune response. Transcriptomic analysis of H5N1-infected monkey lungs showed that certain PI3K-related genes were up-regulated.
| S-EPMC4086889 | biostudies-literature
Project description:After reports of unusually high mortality rates among ducks on farms in Java Island, Indonesia, in September 2012, influenza A(H5N1) viruses were detected and characterized. Sequence analyses revealed all genes clustered with contemporary clade 2.3.2.1 viruses, rather than enzootic clade 2.1.3 viruses, indicating the introduction of an exotic H5N1 clade into Indonesia.
| S-EPMC3966381 | biostudies-literature
Project description:If highly pathogenic H5N1 influenza viruses acquire affinity for human rather than avian respiratory epithelium, will their susceptibility to neuraminidase (NA) inhibitors (the likely first line of defense against an influenza pandemic) change as well? Adequate pandemic preparedness requires that this question be answered. We generated and tested 31 recombinants of A/Vietnam/1203/04 (H5N1) influenza virus carrying single, double, or triple mutations located within or near the receptor binding site in the hemagglutinin (HA) glycoprotein that alter H5 HA binding affinity or specificity. To gain insight into how combinations of HA and NA mutations can affect the sensitivity of H5N1 virus to NA inhibitors, we also rescued viruses carrying the HA changes together with the H274Y NA substitution, which was reported to confer resistance to the NA inhibitor oseltamivir. Twenty viruses were genetically stable. The triple N158S/Q226L/N248D HA mutation (which eliminates a glycosylation site at position 158) caused a switch from avian to human receptor specificity. In cultures of differentiated human airway epithelial (NHBE) cells, which provide an ex vivo model that recapitulates the receptors in the human respiratory tract, none of the HA-mutant recombinants showed reduced susceptibility to antiviral drugs (oseltamivir or zanamivir). This finding was consistent with the results of NA enzyme inhibition assay, which appears to predict influenza virus susceptibility in vivo. Therefore, acquisition of human-like receptor specificity does not affect susceptibility to NA inhibitors. Sequence analysis of the NA gene alone, rather than analysis of both the NA and HA genes, and phenotypic assays in NHBE cells are likely to adequately identify drug-resistant H5N1 variants isolated from humans during an outbreak.
| S-EPMC2276691 | biostudies-literature
Project description:Avian influenza viruses (AIV) potentially transmit to swine as shown by experiments, where further reassortment may contribute to the generation of pandemic strains. Associated risks of AIV inter-species transmission are greater in countries like Nigeria with recurrent epidemics of highly pathogenic AI (HPAI) in poultry and significant pig population. Analysis of 129 tracheal swab specimens collected from apparently healthy pigs at slaughterhouse during presence of HPAI virus H5N1 in poultry in Nigeria for influenza A by RT-qPCR yielded 43 positive samples. Twenty-two could be determined by clade specific RT-qPCR as belonging to the H5N1 clade 2.3.2.1c and confirmed by partial hemagglutinin (HA) sequence analysis. In addition, 500 swine sera were screened for antibodies against influenza A virus nucleoprotein and H5 HA using competition ELISAs and hemagglutination inhibition (HI) tests. Serologically, 222 (44.4%) and 42 (8.4%) sera were positive for influenza A virus NP and H5 antibodies, respectively. Sera reacted to H5N1 and A/H1N1pdm09 strains by HI suggesting exposure of the Nigerian domestic pig population to these viruses. We report for the first time in Nigeria, exposure of domestic pigs to H5N1 virus. This poses potential public health and pandemic risk due to interspecies transmission of avian and human influenza viruses.
| S-EPMC5897404 | biostudies-literature