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Interferon Regulatory Factor 1 and Type I Interferon Cooperate To Control Acute Gammaherpesvirus Infection. J Virol 2017 Jan 01;91(1)

Date

11/01/2016

Pubmed ID

27795415

Pubmed Central ID

PMC5165188

DOI

10.1128/JVI.01444-16

Scopus ID

2-s2.0-85008186468   3 Citations

Abstract

: Gammaherpesviruses are ubiquitous pathogens that establish lifelong infection in >95% of adults worldwide and are associated with a variety of malignancies. Coevolution of gammaherpesviruses with their hosts has resulted in an intricate relationship between the virus and the host immune system, and perturbation of the virus-host balance results in pathology. Interferon regulatory factor 1 (IRF-1) is a tumor suppressor that is also involved in the regulation of innate and adaptive immune responses. Here, we show that type I interferon (IFN) and IRF-1 cooperate to control acute gammaherpesvirus infection. Specifically, we demonstrate that a combination of IRF-1 and type I IFN signaling ensures host survival during acute gammaherpesvirus infection and supports IFN gamma-mediated suppression of viral replication. Thus, our studies reveal an intriguing cross talk between IRF-1 and type I and II IFNs in the induction of the antiviral state during acute gammaherpesvirus infection.

IMPORTANCE: Gammaherpesviruses establish chronic infection in a majority of adults, and this long-term infection is associated with virus-driven development of a range of malignancies. In contrast, a brief period of active gammaherpesvirus replication during acute infection of a naive host is subclinical in most individuals. Here, we discovered that a combination of type I interferon (IFN) signaling and interferon regulatory factor 1 (IRF-1) expression is required to ensure survival of a gammaherpesvirus-infected host past the first 8 days of infection. Specifically, both type I IFN receptor and IRF-1 expression potentiated antiviral effects of type II IFN to restrict gammaherpesvirus replication in vivo, in the lungs, and in vitro, in primary macrophage cultures.

Author List

Mboko WP, Rekow MM, Ledwith MP, Lange PT, Schmitz KE, Anderson S, Tarakanova VL

Author

Vera Tarakanova PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antigens, Differentiation, Myelomonocytic
Antigens, Nuclear
Gammaherpesvirinae
Gene Expression Regulation
Herpesviridae Infections
Host-Pathogen Interactions
Humans
Interferon Regulatory Factor-1
Interferon Regulatory Factor-3
Interferon Regulatory Factor-7
Interferon-Induced Helicase, IFIH1
Interferon-alpha
Interferon-beta
Interferon-gamma
Lung
Macrophages
Mice
Mice, Inbred C57BL
Mice, Knockout
Primary Cell Culture
Proteins
Receptor, Interferon alpha-beta
Signal Transduction
Spleen
Survival Analysis
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a