Publications by authors named "L Keleta"
Article Synopsis
- * It was found that A/turkey/Ontario/6213/1966 (H5N1), isolated shortly before H5N9, is the closest genetic relative and has six genome segments in common.
- * The findings reveal that H5N1 was more virulent than H5N9 in animal models, helping identify it as the key ancestral virus for understanding the development of pathogenic avian influenza strains in North America. *
Most monoclonal antibodies (mAbs) generated from humans infected or vaccinated with the 2009 pandemic H1N1 (pdmH1N1) influenza virus targeted the hemagglutinin (HA) stem. These anti-HA stem mAbs mostly used IGHV1-69 and bound readily to epitopes on the conventional seasonal influenza and pdmH1N1 vaccines. The anti-HA stem mAbs neutralized pdmH1N1, seasonal influenza H1N1 and avian H5N1 influenza viruses by inhibiting HA-mediated fusion of membranes and protected against and treated heterologous lethal infections in mice with H5N1 influenza virus.
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- The study investigated the role of the NS1 protein in enhancing the virulence of influenza A by adapting a specific virus strain (A/Hong Kong/1/1968) in mice, resulting in the identification of multiple mutations in the NS1 and NEP genes.
- The NS1 mutations significantly increased virus replication in mouse cells and correlated with higher virulence, as evidenced by decreased survival and weight loss in infected mice, while also improving the virus's ability to evade the immune response by antagonizing IFN-β production.
- Despite all identified NS1 mutations enhancing viral function, some mutants exhibited reduced binding to a key factor (CPSF30), suggesting a complex relationship between NS1
Adaptive evolution is characterized by positive and parallel, or repeated selection of mutations. Mouse adaptation of influenza A virus (IAV) produces virulent mutants that demonstrate positive and parallel evolution of mutations in the hemagglutinin (HA) receptor and non-structural protein 1 (NS1) interferon antagonist genes. We now present a genomic analysis of all 11 genes of 39 mouse adapted IAV variants from 10 replicate adaptation experiments.
View Article and Find Full Text PDFBackground: To understand the evolutionary steps required for a virus to become virulent in a new host, a human influenza A virus (IAV), A/Hong Kong/1/68(H3N2) (HK-wt), was adapted to increased virulence in the mouse. Among eleven mutations selected in the NS1 gene, two mutations F103L and M106I had been previously detected in the highly virulent human H5N1 isolate, A/HK/156/97, suggesting a role for these mutations in virulence in mice and humans.
Results: To determine the selective advantage of these mutations, reverse genetics was used to rescue viruses containing each of the NS1 mouse adapted mutations into viruses possessing the HK-wt NS1 gene on the A/PR/8/34 genetic backbone.