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ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Exotic & Emerging Avian Viral Diseases Research » Research » Research Project #428435

Research Project: Evolution of the High Pathogenicity Phenotype in Avian Influenza Virus

Location: Exotic & Emerging Avian Viral Diseases Research

Project Number: 6040-32000-066-02-I
Project Type: Interagency Reimbursable Agreement

Start Date: Feb 1, 2015
End Date: Jan 31, 2020

Objective:
The objective of this US-UK collaborative study is to elucidate the mechanisms behind the evolution of the high pathogenicity phenotype in avian influenza virus. The overall problem we are addressing is that of understanding the evolutionary pathways followed by avian influenza viruses in poultry that lead to the switch from an LPAI to an HPAI phenotype. We will test the hypothesis that specific alterations to the viral M2 ion channel protein are necessary to support the virulent HA function, both in vitro and in vivo. We will also evaluate whether or not these changes to M2 have implications for “universal” AIV vaccine strategies.

Approach:
We wish to understand the influence the viral M2 ion channel exerts on the interplay between HA proteolytic activation, glycosylation and pH sensitivity and how these factors combine to alter virulence and transmissibility of the virus. It is clear that the increased cleavability of the HA is key to the HPAI phenotype, but that it often comes at a cost of decreased pH stability and thus increased dependence on the pH-modulating effects of M2. We will use the A/chicken/Pennsylvania/83 lineage of viruses as a model system in which to explore this because they exhibit the twin properties of (a) HA glycosylation masking of the HPAI phenotype and (b) expressing the M42 form of the ion channel. Following on from this, we will also explore whether the ability of some strain of AIV to express M42 in preference to M2 has implications for ‘universal’ vaccination strategies directed against M2e.