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Human parainfluenza virus type 2 V protein inhibits interferon production and signaling and is required for replication in non-human primates.

Abstract：

:In wild-type human parainfluenza virus type 2 (WT HPIV2), one gene (the P/V gene) encodes both the polymerase-associated phosphoprotein (P) and the accessory V protein. We generated a HPIV2 virus (rHPIV2-V(ko)) in which the P/V gene encodes only the P protein to examine the role of V in replication in vivo and as a potential live attenuated virus vaccine. Preventing expression of V protein severely impaired virus recovery from cDNA and growth in vitro, particularly in IFN-competent cells. rHPIV2-V(ko), unlike WT HPIV2, strongly induced IFN-beta and permitted IFN signaling, leading to establishment of a robust antiviral state. rHPIV2-V(ko) infection induced extensive syncytia and cytopathicity that was due to both apoptosis and necrosis. Replication of rHPIV2-V(ko) was highly restricted in the respiratory tract of African green monkeys and in differentiated primary human airway epithelial (HAE) cultures, suggesting that V protein is essential for efficient replication of HPIV2 in organized epithelial cells and that rHPIV2-V(ko) is over-attenuated for use as a live attenuated vaccine.

journal_name

Virology

journal_title

Virology

authors

Schaap-Nutt A,D'Angelo C,Scull MA,Amaro-Carambot E,Nishio M,Pickles RJ,Collins PL,Murphy BR,Schmidt AC

doi

10.1016/j.virol.2009.11.018

subject

Has Abstract

pub_date

2010-02-20 00:00:00

pages

285-98

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(09)00729-6

journal_volume

397

pub_type

杂志文章

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