RESUMO
The influenza A viral heterotrimeric polymerase complex (PA, PB1, PB2) is known to be involved in many aspects of viral replication and to interact with host factors, thereby having a role in host specificity. The polymerase protein sequences from the 1918 human influenza virus differ from avian consensus sequences at only a small number of amino acids, consistent with the hypothesis that they were derived from an avian source shortly before the pandemic. However, when compared to avian sequences, the nucleotide sequences of the 1918 polymerase genes have more synonymous differences than expected, suggesting evolutionary distance from known avian strains. Here we present sequence and phylogenetic analyses of the complete genome of the 1918 influenza virus, and propose that the 1918 virus was not a reassortant virus (like those of the 1957 and 1968 pandemics), but more likely an entirely avian-like virus that adapted to humans. These data support prior phylogenetic studies suggesting that the 1918 virus was derived from an avian source. A total of ten amino acid changes in the polymerase proteins consistently differentiate the 1918 and subsequent human influenza virus sequences from avian virus sequences. Notably, a number of the same changes have been found in recently circulating, highly pathogenic H5N1 viruses that have caused illness and death in humans and are feared to be the precursors of a new influenza pandemic. The sequence changes identified here may be important in the adaptation of influenza viruses to humans.
Assuntos
Evolução Molecular , Genes Virais/genética , Vírus da Influenza A/enzimologia , Vírus da Influenza A/genética , Influenza Humana/história , Influenza Humana/virologia , RNA Polimerase Dependente de RNA/genética , Adaptação Fisiológica/genética , Substituição de Aminoácidos/genética , Animais , Aves/virologia , Genoma Viral , História do Século XX , Humanos , Vírus da Influenza A/patogenicidade , Influenza Humana/epidemiologia , Mutação/genética , Filogenia , RNA Polimerase Dependente de RNA/química , Vírus Reordenados/genética , Fatores de Tempo , Proteínas Virais/química , Proteínas Virais/genética , Replicação Viral/genéticaRESUMO
The nucleoprotein (NP) gene of the 1918 pandemic influenza A virus has been amplified and sequenced from archival material. The NP gene is known to be involved in many aspects of viral function and to interact with host proteins, thereby playing a role in host specificity. The 1918 NP amino acid sequence differs at only six amino acids from avian consensus sequences, consistent with reassortment from an avian source shortly before 1918. However, the nucleotide sequence of the 1918 NP gene has more than 170 differences from avian strain consensus sequences, suggesting substantial evolutionary distance from known avian strain sequences. Both the gene and protein sequences of the 1918 NP fall within the mammalian clade upon phylogenetic analysis. The evolutionary distance of the 1918 NP sequences from avian and mammalian strain sequences is examined, using several different parameters. The results suggest that the 1918 strain did not retain the previously circulating human NP. Nor is it likely to have obtained its NP by reassortment with an avian strain similar to those now characterized. The results are consistent with the existence of a currently unknown host for influenza, with an NP similar to current avian strain NPs at the amino acid level but with many synonymous nucleotide differences, suggesting evolutionary isolation from the currently characterized avian influenza virus gene pool.
Assuntos
Nucleoproteínas/genética , Proteínas de Ligação a RNA/genética , Proteínas do Core Viral/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Humanos , Influenza Humana/epidemiologia , Dados de Sequência Molecular , Proteínas do Nucleocapsídeo , Nucleoproteínas/química , Orthomyxoviridae/classificação , Filogenia , Proteínas de Ligação a RNA/química , Análise de Regressão , Suínos , Fatores de Tempo , Proteínas do Core Viral/químicaAssuntos
Surtos de Doenças/história , Influenza Humana/história , Sequência de Aminoácidos , Sequência de Bases , DNA Viral/genética , Genes Virais , Variação Genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/fisiologia , História do Século XX , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Vírus da Influenza A/fisiologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Dados de Sequência Molecular , América do Norte/epidemiologia , Receptores Virais/fisiologiaRESUMO
Severe acute respiratory syndrome (SARS) is an infectious condition caused by the SARS-associated coronavirus (SARS-CoV), a new member in the family Coronaviridae. To evaluate the lung pathology in this life-threatening respiratory illness, we studied postmortem lung sections from 8 patients who died from SARS during the spring 2003 Singapore outbreak. The predominant pattern of lung injury in all 8 cases was diffuse alveolar damage. The histology varied according to the duration of illness. Cases of 10 or fewer days' duration demonstrated acute-phase diffuse alveolar damage (DAD), airspace edema, and bronchiolar fibrin. Cases of more than 10 days' duration exhibited organizing-phase DAD, type II pneumocyte hyperplasia, squamous metaplasia, multinucleated giant cells, and acute bronchopneumonia. In acute-phase DAD, pancytokeratin staining was positive in hyaline membranes along alveolar walls and highlighted the absence of pneumocytes. Multinucleated cells were shown to be both type II pneumocytes and macrophages by pancytokeratin, thyroid transcription factor-1, and CD68 staining. SARS-CoV RNA was identified by reverse transcriptase-polymerase chain reaction in 7 of 8 cases in fresh autopsy tissue and in 8 of 8 cases in formalin-fixed, paraffin-embedded lung tissue, including the 1 negative case in fresh tissue. Understanding the pathology of DAD in SARS patients may provide the basis for therapeutic strategies. Further studies of the pathogenesis of SARS may reveal new insight into the mechanisms of DAD.
