Biological fitness and natural selection of amantadine resistant variants of avian influenza H5N1 viruses.

Abstract:

:Outbreaks caused by the highly pathogenic H5N1 avian influenza virus (A/H5N1) devastated the poultry industry in several countries and posed a significant pandemic threat. In addition to culling of infected poultry and vaccination, amantadine has been applied in poultry in some countries to control the spread of the virus. The prevalence of the amantadine resistance marker at position 31 (Ser31Asn) of the M2 protein increased over time. However, little is known about the biological fitness and selection of H5N1 amantadine resistant strains over their sensitive counterparts. Here, using reverse genetics we investigated the biological impact of Ser31Asn in M2 commonly seen in viruses in clade 2.2.1.1 in farmed poultry in Egypt. Findings of the current study indicated that the resistance to amantadine conferred by Asn31 evolved rapidly after the application of amantadine in commercial poultry. Both the resistant and sensitive strains replicated at similar levels in avian cell culture. Asn31 increased virus entry into the cells and cell-to-cell spread and was genetically stable for several passages in cell culture. Moreover, upon co-infection of cell culture resistant strains dominated sensitive viruses even in the absence of selection by amantadine. Together, rapid emergence, stability and domination of amantadine-resistant variants over sensitive strains limit the efficacy of amantadine in poultry.

journal_name

Virus Res

journal_title

Virus research

authors

Abdelwhab EM,Veits J,Mettenleiter TC

doi

10.1016/j.virusres.2016.11.032

subject

Has Abstract

pub_date

2017-01-15 00:00:00

pages

109-113

eissn

0168-1702

issn

1872-7492

pii

S0168-1702(16)30504-4

journal_volume

228

pub_type

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