Skip to main content

This is a preprint.

It has not yet been peer reviewed by a journal.

The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

bioRxiv logoLink to bioRxiv
[Preprint]. 2024 Aug 19:2024.08.19.606826. [Version 1] doi: 10.1101/2024.08.19.606826

Enhanced Diversifying Selection on Polymerase Genes in H5N1 Clade 2.3.4.4b: A Key Driver of Altered Species Tropism and Host Range Expansion

Sougat Misra, Elizabeth Gilbride, Santhamani Ramasamy, Sergei L Kosakovsky Pond, Suresh V Kuchipudi
PMCID: PMC11370473  PMID: 39229076

Abstract

Highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses have shown unprecedented host range and pathogenicity, including infections in cattle, previously not susceptible to H5N1. We investigated whether selection pressures on clade 2.3.4.4b viral genes could shed light on their unique epidemiological features. Our analysis revealed that while the gene products of clade 2.3.4.4b H5N1 primarily undergo purifying selection, there are notable instances of episodic diversifying selection. Specifically, the polymerase genes PB2, PB1, and PA exhibit significantly greater selection pressures in clade 2.3.4.4b than all earlier H5N1 virus clades. Polymerases play critical roles in influenza virus adaptation, including viral fitness, interspecies transmission, and virulence. Our findings provide evidence that significant selection pressures have shaped the evolution of the H5N1 clade 2.3.4.4b viruses, facilitating their expanded host tropism and the potential for further adaptation to mammalian hosts. We discuss how exogenous factors, such as altered bird migration patterns and increased host susceptibility, may have contributed to the expanded host range. As H5N1 viruses continue to infect new hosts, there is a greater risk of emergent novel variants with increased pathogenicity in humans and animals. Thus, comprehensive One Health surveillance is critical to monitor transmission among avian and mammalian hosts.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


Articles from bioRxiv are provided here courtesy of Cold Spring Harbor Laboratory Preprints

RESOURCES