Human parainfluenza virus type 2 V protein inhibits interferon production and signaling and is required for replication in non-human primates.
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.
Schaap-Nutt
Anne
A
Laboratory of Infectious Diseases, RNA Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. schaapa@niaid.nih.gov
D'Angelo
Christopher
C
Scull
Margaret A
MA
Amaro-Carambot
Emerito
E
Nishio
Machiko
M
Pickles
Raymond J
RJ
Collins
Peter L
PL
Murphy
Brian R
BR
Schmidt
Alexander C
AC
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D007372:Interferons / Q000276:immunology*; D008992:Monkey Diseases / Q000473:pathology / Q000821:virology; D010223:Parainfluenza Virus 2, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D012141:Respiratory Tract Infections / Q000473:pathology / Q000821:virology; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D014779:Virus Replication
C068854:V protein, human parainfluenza virus type 1; D014764:Viral Proteins; D007372:Interferons