Consortium of 'consistent amino acid substitutions' on influenza A (H1N1) viral proteins emerged at specific stages of viral infection: a big data analysis.

Abstract

Influenza A (H1N1) virus has been one of the most common threats to humankind since 1918. The viral genome is frequently substituted, leading to new strains and recurrent pandemics. Despite knowing the effects of single amino acid substitutions on individual viral proteins, the effects of collective substitutions on viral infection remain elusive. Here, we addressed whether the 'consistent amino acid substitutions' occur in a consortium on functional domains and protein-protein interaction (PPI) sites, impacting overall viral infection and host immune responses. By definition, 'consistent substitutions' occur on 'all' the Influenza A (H1N1) viral strains isolated in a particular year. To address this question, big protein data (563370 sequences and 9824 PPI) were analysed using multiple sequence alignment, text mining, protein structure analyses etc. A total of one hundred and five 'consistent substitutions' were mapped on the ten viral proteins of influenza A(H1N1) pdm09 strain. Fifty of those emerged on viral protein functional domains and PPIs, engaged in the specific stages of the viral infection, namely, i) cell surface entry and exit, ii) nuclear import, vRNP assembly, and nuclear export, and iii) antagonizing immune responses. For the first time, the study showed that a consortium of 'consistent substitutions' emerged on protein functional domains and PPIs, impacting specific stages of viral infection rather than a single protein and presumably navigating viral escape from human immune response.