Abstract
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which can be activated by cytokines, growth factor receptors, and nonreceptor-like tyrosine kinase. An activated STAT3 translocates into the nucleus and combines with DNA to regulate the expression of target genes involved in cell proliferation, differentiation, apoptosis and metastasis. Recent studies have shown that STAT3 plays important roles in viral infection and pathogenesis. STAT3 exhibits a proviral function in several viral infections, including those of HBV, HCV, HSV-1, varicella zoster virus, human CMV and measles virus. However, in some circumstances, STAT3 has an antiviral function in other viral infections, such as enterovirus 71, severe acute respiratory syndrome coronavirus and human metapneumovirus. This review summarizes the roles of STAT3 in viral infection and pathogenesis, and briefly discusses the molecular mechanisms involved in these processes.
Highlights
STAT3 signaling is mainly activated by the IL-6 and IL-10 family cytokines and growth factor receptors
STAT3 phosphorylated at Tyr705 is required for dimerization to activate STAT3 signaling, which would be inhibited by suppressor of cytokine signaling, protein inhibitor of activated STAT and protein tyrosine phosphatase
In some circumstances, STAT3 has an antiviral activity in other viral infections
Summary
Role of STAT3 in viral infection STAT3 can be activated by IL-6 and IL-10 family cytokines and growth factors [10]. The role of STAT3 in viral infection is complicated, and various viruses cause differences in the host cell STAT3 activation (Table 1 & Figure 3). STAT3 participates in host antiviral immune response, and in the inflammatory responses induced by viruses. The role of STAT3 in virus replication is uncertain and seems to function as a proviral or antiviral factor in a virus-specific manner (Table 1). STAT3 in hepatitis B & C virus infection STAT3 can be activated by HBV, HCV and several oncogenes [37,44,46]. HBV or HCV infection is the major risk factor of hepatocellular carcinoma (HCC) [94]. HBV-induced primary liver cancer, advanced liver cancer recurrence and metastasis are associated with persistent inflammation accompanying the
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