Mutations within the human parainfluenza virus type 3 (HPIV 3) C protein affect viral replication and host interferon induction.
Human parainfluenza virus type 3 (HPIV 3) encodes a multifunctional C protein that is capable of inhibiting viral replication and counteracting the host interferon (IFN) signaling pathway. We recently demonstrated that the C protein is phosphorylated both in vitro and in vivo and mutations within the phosphorylation sites exhibit differential inhibitory activities in vitro. In this study, we report for the first time the successful recovery of mutant HPIV 3 viruses containing mutations within the C protein. Three mutant viruses, Cm-1, Cm-3 and Cm-4, harboring individual mutations of S7, S47T48 and S81 residues, respectively, were examined for their replication profiles and their ability to abrogate host IFN induction. Viral transcription was similar for all viruses; however Cm-3 displayed a relatively higher replication. Infection of cells with Cm-1 and Cm-3 led to the activation of IFN regulatory transcription factor 3 (IRF-3) and subsequent increase in IFN-β mRNA levels as determined by immunofluorescence assay and RT-PCR analyses, respectively. Moreover, Cm-3 was able to partially resist the interferon induced antiviral state in Vero cells. Taken together, these results suggest that mutations within the C protein differentially affect viral replication and host interferon induction.
Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA.
Greg
G
Wells
Matthew
M
Addington-Hall
Achut G
AG
Malur
D000818:Animals; D002522:Chlorocebus aethiops; D020869:Gene Expression Profiling; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology*; D020125:Mutation, Missense; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D060888:Real-Time Polymerase Chain Reaction; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication
D050838:Interferon Regulatory Factor-3; D014764:Viral Proteins; D016899:Interferon-beta