Recombinant Human Parainfluenza Virus Type 2 with Mutations in V That Permit Cellular Interferon Signaling Are Not Attenuated in Non-human Primates

Overview

Journal Virology

Specialty Microbiology

Date 2010 Jul 30

PMID 20667570

Citations 6

Authors

Anne Schaap-Nutt

Christopher DAngelo

Emerito Amaro-Carambot

Sheila M Nolan

Stephanie Davis

Shenelle-Marie Wise

Caraline Higgins

Konrad Bradley

Olivia Kim

Reina Mayor

Mario H Skiadopoulos

Peter L Collins

Brian R Murphy

Alexander C Schmidt

Affiliations

Soon will be listed here.

Abstract

The HPIV2 V protein inhibits type I interferon (IFN) induction and signaling. To manipulate the V protein, whose coding sequence overlaps that of the polymerase-associated phosphoprotein (P), without altering the P protein, we generated an HPIV2 virus in which P and V are expressed from separate genes (rHPIV2-P+V). rHPIV2-P+V replicated like HPIV2-WT in vitro and in non-human primates. HPIV2-P+V was modified by introducing two separate mutations into the V protein to create rHPIV2-L101E/L102E and rHPIV2-Delta122-127. In contrast to HPIV2-WT, both mutant viruses were unable to degrade STAT2, leaving virus-infected cells susceptible to IFN. Neither mutant, nor HPIV2-WT, induced significant amounts of IFN-beta in infected cells. Surprisingly, neither rHPIV2-L101E/L102E nor rHPIV2-Delta122-127 was attenuated in two species of non-human primates. This indicates that loss of HPIV2's ability to inhibit IFN signaling is insufficient to attenuate virus replication in vivo as long as IFN induction is still inhibited.

Citing Articles

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