Viral interferon regulatory factors decrease the induction of type I and type II interferon during rhesus macaque rhadinovirus infection.

Abstract

Kaposi's sarcoma-associated herpesvirus and rhesus macaque rhadinovirus (RRV), two closely related gammaherpesviruses, are unique in their expression of viral homologs of cellular interferon regulatory factors (IRFs), termed viral IRFs (vIRFs). To assess the role of vIRFs during de novo infection, we have utilized the bacterial artificial chromosome clone of wild-type RRV(17577) (WT(BAC) RRV) to generate a recombinant virus with all 8 of the vIRFs deleted (vIRF-ko RRV). The infection of primary rhesus fibroblasts and peripheral blood mononuclear cells (PBMCs) with vIRF-ko RRV resulted in earlier and increased induction of type I interferon (IFN) (IFN-α/β) and type II IFN (IFN-γ). Additionally, plasmacytoid dendritic cells maintained higher levels of IFN-α production in PBMC cultures infected with vIRF-ko RRV than in cultures infected with WT(BAC) RRV. Moreover, the nuclear accumulation of phosphorylated IRF-3, which is necessary for the induction of type I IFN, was also inhibited following WT(BAC) RRV infection. These findings demonstrate that during de novo RRV infection, vIRFs are inhibiting the induction of IFN at the transcriptional level, and one potential mechanism for this is the disruption of the activation and localization of IRF-3.

• Authors: Bridget A Robinson, Ryan D Estep, Ilhem Messaoudi, Kelsey S Rogers, Scott W Wong
• Journal: Journal of virology (J Virol) Vol. 86 Issue 4 Pg. 2197-211 (Feb 2012) ISSN: 1098-5514 [Electronic] United States
• PMID: 22156526 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interferon Regulatory Factor-3
• Interferon Regulatory Factors
• Interferon Type I
• Viral Proteins
• viral interferon regulatory factors
• Interferon-gamma

Topics

• Animals
• Cell Line
• Down-Regulation
• Herpesviridae Infections (genetics, metabolism, veterinary, virology)
• Interferon Regulatory Factor-3 (genetics, metabolism)
• Interferon Regulatory Factors (genetics, metabolism)
• Interferon Type I (genetics, metabolism)
• Interferon-gamma (genetics, metabolism)
• Macaca mulatta
• Primate Diseases (genetics, metabolism, virology)
• Rhadinovirus (genetics, physiology)
• Viral Proteins (genetics, metabolism)