Persistent Host Markers in Pandemic and H5N1 Influenza Viruses

TLDR

Avian influenza viruses have adapted to humans, causing pandemics, yet the specific host‑specific amino acid mutations enabling this adaptation remain unknown. By performing multiple‑sequence alignment and statistical testing of each aligned amino acid, the authors identified markers that discriminate human from avian influenza viruses and retained only those highly preserved in human isolates over time. A subset of these persistent host markers is present in all human pandemic influenza virus sequences from 1918, 1957, and 1968, while others emerge as the virus becomes seasonal; human H5N1 viruses are more likely to carry the human‑predominant amino acids for some markers, indicating modest recent adaptation and suggesting these markers can aid monitoring of potential pandemic strains.

Abstract

Avian influenza viruses have adapted to human hosts, causing pandemics in humans. The key host-specific amino acid mutations required for an avian influenza virus to function in humans are unknown. Through multiple-sequence alignment and statistical testing of each aligned amino acid, we identified markers that discriminate human influenza viruses from avian influenza viruses. We applied strict thresholds to select only markers which are highly preserved in human influenza virus isolates over time. We found that a subset of these persistent host markers exist in all human pandemic influenza virus sequences from 1918, 1957, and 1968, while others are acquired as the virus becomes a seasonal influenza virus. We also show that human H5N1 influenza viruses are significantly more likely to contain the amino acid predominant in human strains for a few persistent host markers than avian H5N1 influenza viruses. This sporadic enrichment of amino acids present in human-hosted viruses may indicate that some H5N1 viruses have made modest adaptations to their new hosts in the recent past. The markers reported here should be useful in monitoring potential pandemic influenza viruses.