Inhibition of influenza A virus matrix and nonstructural gene expression using RNA interference.

Abstract:

:Influenza antiviral drugs that use protein inhibitors can lose their efficacy as resistant strains emerge. As an alternative strategy, we investigated the use of small interfering RNA molecules (siRNAs) by characterizing three siRNAs (M747, M776 and M832) targeting the influenza matrix 2 gene and three (NS570, NS595 and NS615) targeting the nonstructural protein 1 and 2 genes. We also re-examined two previously reported siRNAs, M331 and M950, which target the matrix 1 and 2 genes. Treatment with M331-, M776-, M832-, and M950-siRNAs attenuated influenza titer. M776-siRNA treated cells had 29.8% less infectious virus than cells treated with the previously characterized siRNA, M950. NS570-, NS595- and NS615-siRNAs reduced nonstructural protein 1 and 2 expression and enhanced type I interferon expression by 50%. Combination siRNA treatment attenuated 20.9% more infectious virus than single siRNA treatment. Our results suggest a potential use for these siRNAs as an effective anti-influenza virus therapy.

journal_name

Virology

journal_title

Virology

authors

McMillen CM,Beezhold DH,Blachere FM,Othumpangat S,Kashon ML,Noti JD

doi

10.1016/j.virol.2016.07.019

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

171-184

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(16)30188-X

journal_volume

497

pub_type

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