RESUMO
Since the emergence of the pandemic H1N1pdm09 virus in Mexico and California, biannual increases in the number of cases have been detected in Mexico. As observed in previous seasons, pandemic A/H1N1 09 virus was detected in severe cases during the 2011-2012 winter season and finally, during the 2013-2014 winter season it became the most prevalent influenza virus. Molecular and phylogenetic analyses of the whole viral genome are necessary to determine the antigenic and pathogenic characteristics of influenza viruses that cause severe outcomes of the disease. In this paper, we analyzed the evolution, antigenic and genetic drift of Mexican isolates from 2009, at the beginning of the pandemic, to 2014. We found a clear variation of the virus in Mexico from the 2011-2014 season due to different markers and in accordance with previous reports. In this study, we identified 13 novel substitutions with important biological effects, including virulence, T cell epitope presented by MHC and host specificity shift and some others substitutions might have more than one biological function. The systematic monitoring of mutations on whole genome of influenza A pH1N1 (2009) virus circulating at INER in Mexico City might provide valuable information to predict the emergence of new pathogenic influenza virus.
Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , Estações do Ano , Substituição de Aminoácidos/genética , Antígenos Virais/imunologia , Demografia , Feminino , Genoma Viral , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Funções Verossimilhança , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Filogenia , Prevalência , Análise de Sequência de DNARESUMO
BACKGROUND: A characteristic difference between highly and non-highly pathogenic avian influenza strains is the presence of an extended, often multibasic, cleavage motif insertion in the hemagglutinin protein. Such motif is found in H7N3 strains from chicken farm outbreaks in 2012 in Mexico. METHODS: Through phylogenetic, sequence and structural analysis, we try to shed light on the role, prevalence, likelihood of appearance and origin of the inserted cleavage motifs in these H7N3 avian influenza strains. RESULTS: The H7N3 avian influenza strain which caused outbreaks in chicken farms in June/July 2012 in Mexico has a new extended cleavage site which is the likely reason for its high pathogenicity in these birds. This cleavage site appears to have been naturally acquired and was not present in the closest low pathogenic precursors. Structural modeling shows that insertion of a productive cleavage site is quite flexible to accept insertions of different length and with sequences from different possible origins. Different from recent cleavage site insertions, the origin of the insert here is not from the viral genome but from host 28S ribosomal RNA (rRNA) instead. This is a novelty for a natural acquisition as a similar insertion has so far only been observed in a laboratory strain before. Given the abundance of viral and host RNA in infected cells, the acquisition of a pathogenicity-enhancing extended cleavage site through a similar route by other low-pathogenic avian strains in future does not seem unlikely. Important for surveillance of these H7N3 strains, the structural sites known to enhance mammalian airborne transmission are dominated by the characteristic avian residues and the risk of human to human transmission should currently be low but should be monitored for future changes accordingly. CONCLUSIONS: This highly pathogenic H7N3 avian influenza strain acquired a novel extended cleavage site which likely originated from recombination with 28S rRNA from the avian host. Notably, this new virus can infect humans but currently lacks critical host receptor adaptations that would facilitate human to human transmission.