Molecular Characterization Of H1N1 Influenza A Viruses From Human Cases In North America And Global Spread Mode Of Human Highly Pathogenic H5N1 Avian Influenza Virus

Subtypes of H1N1 influenza virus can be found in humans in North America, while they are also associated with the infection of swine. Characterization of the genotypes of viral strains in human populations is important to understand the source and distribution of viral strains. Genomic and protein sequences of 10 isolates of the 2009 outbreak of influenza A (H1N1) virus in North America were obtained from GenBank database. To characterize the genotypes of these viruses, phylogenetic trees of genes PB2, PB1, PA, HA, NP, NA, NS and M were constructed by Phylip3.67 program and N-Linked glycosylation sites of HA, NA, PB2, NS1 and M2 proteins were analyzed online by NetNGlyc1.0 program. Phylogenetic analysis indicated that these isolates are virtually identical but may be recombinant viruses because their genomic fragments come from different viruses. The isolates also contain a characteristic lowly pathogenic amino acid motif at their HA cleavage sites (IPSIQSR↓GL), and an E residue at position 627 of the PB2 protein which shows its high affinity to humans. The homologous model of M2 proteins showed that the viruses had obtained the ability of anti-amantadine due to the mutation at the drug-sensitive site, while sequence analysis of NA proteins indicated that the viruses are still susceptible to the neuraminidase inhibitor drug (i.e. oseltamivir and zanamivir) because no mutations have been observed. Our results strongly suggested that the viruses responsible for the 2009 outbreaks of influenza A (H1N1) virus have the ability to cross species barriers to infect human and mammalian animals based on molecular analysis. These findings may further facilitate the therapy and prevention of possible transmission from North America to other countries.Highly pathogenic avian influenza virus of type A of subtype H5N1(HPAI H5N1) is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus. A global effort is underway to control or eradicate HAPI H5N1 in poultry and prevent human exposure, both of which may also reduce the risk of pandemic emergence. Hemagglutinin gene (HA) sequences from 215 human cases of H5N1 were used to trace the source and dispersal pattern of human cases of H5N1 on a global scale. A mutation network and phylogenetic analyses of the HA shows that human H5N1 virus can be clearly divided into four clusters across geographic space. Based on the 100 and 170 N-glycosylation sites in the HA, human H5N1 viruses were also divided into three types. When combined with GIS data analysis, we found Southern China is often a common source of multiple H5N1 clusters and each cluster has different dispersal patterns and individual evolutionary features. In summary, the genetic evidence presented here provides clear evidence for multiple clusters of human H5N1 initially originating from southern China.