Zika virus targets human STAT2 to inhibit type I interferon signaling

By A. Grant, S. S. Ponia, Shashank Tripathi, V. Balasubramaniam, Lisa Miorin, M. Sourisseau, Megan C Schwarz, M. Sánchez-Seco, M. Evans, S. Best and 1 more. Cell Host and Microbe, 2016

744 citations recorded by the source corpus.

Summary The ongoing epidemic of Zika virus (ZIKV) illustrates the importance of flaviviruses as emerging human pathogens. All vector-borne flaviviruses studied thus far have to overcome type I interferon (IFN) to replicate and cause disease in vertebrates. The mechanism(s) by which ZIKV antagonizes IFN signaling is unknown. Here, we report that the nonstructural protein NS5 of ZIKV and other flaviviruses examined could suppress IFN signaling, but through different mechanisms. ZIKV NS5 expression resulted in proteasomal degradation of the IFN-regulated transcriptional activator STAT2 from humans but not mice, which may explain the requirement for IFN-deficiency to observe ZIKV-induced disease in mice. The mechanism of ZIKV NS5 resembles dengue virus (DENV) NS5 and not its closer relative, Spondweni virus (SPOV). However, unlike DENV, ZIKV did not require the E3 ubiquitin ligase UBR4 to induce STAT2 degradation. Hence, flavivirus NS5 proteins exhibit a remarkable functional convergence in IFN antagonism, albeit by virus-specific mechanisms.

Subfields: Infectious Diseases, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/448af08fcbea4779b15c587107e491751cf8641a

Citations in the corpus

• Shared and Distinct Functions of Type I and Type III Interferons (2019, neutral): “This results in part from species restrictions, including the inability of ZIKV to antagonize murine STAT2 and STING proteins (Ding et al., 2018; Gorman et al., 2018; Grant et al., 2016; Kumar et al., 2016).”
• Modified mRNA vaccines protect against Zika virus infection (2017, neutral): “…viremia with IgG titers of ~1/2,000 (Larocca et al., 2016), some of these studies used immunocompetent strains for challenge, which do not support as efficient ZIKV infection due to a species-specific lack of antagonism of IFN signaling (Grant et al., 2016; Kumar et al., 2016; Lazear et al., 2016).”