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Review
. 2015:2015:272359.
doi: 10.1155/2015/272359. Epub 2015 Jun 25.

The Complex Role of STAT3 in Viral Infections

Suresh V Kuchipudi  1
Affiliations
Review

The Complex Role of STAT3 in Viral Infections

Suresh V Kuchipudi. J Immunol Res. 2015.

Abstract

Signal transducer and activators of transcription-3 (STAT3) regulates diverse biological functions including cell growth, differentiation, and apoptosis. In addition, STAT3 plays a key role in regulating host immune and inflammatory responses and in the pathogenesis of many cancers. Several studies reported differential regulation of STAT3 in a range of viral infections. Interestingly, STAT3 appears to direct seemingly contradictory responses and both pro- and antiviral roles of STAT3 have been described. This review summarized the currently known functions of STAT3 in the regulation of viral replication and pathogenesis of viral infections. Some of the key unanswered questions and the gap in our current understanding of the role of STAT3 in viral pathogenesis are discussed.

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Figures

Figure 1
Figure 1
Structure of STAT3. The six domains of STAT3 are N-terminal domain (ND), coiled-coil domain (CCD), DNA-binding domain (DBD), linker domain, SH2 domain, and transcriptional activation domain (TAD). Between SH2 and TAD there is a tail segment that contains the phosphorylation site Y705.
Figure 2
Figure 2
STAT3 signal transduction pathway. In response to cytokines and growth factors, STAT3 is phosphorylated by receptor-associated kinases and then forms homo- or heterodimers. STAT3 dimers then translocate to the nucleus where they act as a transcription activator and mediate the expression of a variety of genes. STAT3 activates the transcription of suppressors of cytokine signalling 3 (SOCS3) which act as classical feedback inhibitor of STAT3 activation.
Figure 3
Figure 3
STAT3 regulation in viral infections. Epstein-Barr virus (EBV) oncoprotein latent membrane protein 1 (LMP1), human immunodeficiency virus type 1 (HIV-1) Nef protein, hepatitis C virus (HCV) core protein, HCV nonstructural protein 5A (NS5A), hepatitis B virus X protein (HBx), Kaposi's sarcoma-associated herpesvirus (KSHV), saimiri transforming protein (STP) oncogene of Herpesvirus saimiri subgroup A strain 11 (STP-A11), and Varicella-zoster virus (VZV) activate STAT3 phosphorylation. Influenza A virus (IAV) nonstructural protein 1 (NS-1) human metapneumovirus (hMPV) and human cytomegalovirus (HCMV) inhibit STAT3 phosphorylation. Severe acute respiratory syndrome coronavirus (SARS-CoV) infection results in STAT3 dephosphorylation.
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