Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection

Abstract

The continuing pandemic threat posed by avian influenza A/H5N1 viruses calls for improved insights into their evolution during human infection. We performed whole genome deep sequencing of respiratory specimens from 44 H5N1-infected individuals from Indonesia and found substantial within-host viral diversity. At nearly 30% of genome positions multiple amino acids were observed within or across samples, including positions implicated in aerosol transmission between ferrets. Amino acid variants detected our cohort were often found more frequently in available H5N1 sequences of human than avian isolates. We additionally identified previously unreported amino acid variants and multiple variants that increased in proportion over time in available sequential samples. Given the importance of the polymerase complex for host adaptation, we tested 121 amino acid variants found in the PB2, PB1 and PA subunits for their effects on polymerase activity in human cells. We identified multiple single amino acid variants in all three polymerase subunits that substantially increase polymerase activity including some with effects comparable to that of the widely recognized adaption and virulence marker PB2-E627 K. These results indicate highly dynamic evolutionary processes during human H5N1 virus infection and the potential existence of previously undocumented adaptive pathways.

Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses

“…As for some human-derived influenza viruses both the (3SL)-and the (6SL)-conjugated PAMAM dendrimers showed an inhibitory effect, we repeated the HAI assay for one of those viruses (BR/59) by mixing the (3SL) 8 -and the (6SL) 8 -PAMAMs but unfortunately, the combination did not result in a reduction of the minimal inhibitory concentration. Hence, a PAMAM dendrimer conjugated to both α2,3and α2,6-linked SA might not increase the inhibitory effect but such broad-specificity inhibitors might be of advantage to inhibit strains of unknown tropism and those with dual receptor specificity, like the avian influenza A(H5N1) 27 or A(H7N9) 28 virus.…”

Asynchrony between virus diversity and antibody selection limits influenza virus evolution

“…These phenotypes affect virus fitness throughout the timecourse of infection, so they can be efficiently replication-selected (where selection is manifest in the direct competition for infecting other cells rather than indirect competition by escaping antibodies). Indeed, next generation sequencing studies have found observable adaptative evolution of non-antigenic phenotypes in individual humans infected with avian H5N1 viruses (Welkers et al, 2019).…”

In silico QSAR and molecular docking simulation of some novel aryl sulfonamide derivatives as inhibitors of H5N1 influenza A virus subtype

“…The influenza infection is also called flu, and there are three (3) key types of the influenza virus namely, A, B, and C which are also classified into different subtypes. The circulating seasonal viruses presently are influenza A (H1N1, H3N2) and influenza B viruses [1]. The European Centre for Disease Prevention and Control (ECDPC) in 2019 published a surveillance report on influenza virus characterization which summarizes the percentage of influenza virus detections in the WHO European Region.…”