C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3

PLoS Neglected Tropical Diseases
Yun WuXun Zhu

Abstract

The rapidly emerging human health crisis associated with the Zika virus (ZIKV) epidemic and its link to severe complications highlights the growing need to identify the mechanisms by which ZIKV accesses hosts. Interferon response protects host cells against viral infection, while the cellular factors that mediate this defense are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified, only a few have been characterized for their antiviral potential, target specificity and mechanisms of action. In this work, we focused our investigation on the possible antiviral effect of a novel ISG, C19orf66 in response to ZIKV infection and the associated mechanisms. We found that ZIKV infection could induce C19orf66 expression in ZIKV-permissive cells, and such an overexpression of C19orf66 remarkably suppressed ZIKV replication. Conversely, the depletion of C19orf66 led to a significant increase in viral replication. Furthermore, C19orf66 was found to interact and co-localize with ZIKV nonstructural protein 3 (NS3), thus inducing NS3 degradation via a lysosome-dependent pathway. Taken together, this study identified C19orf66 as a novel ISG that exerts antiviral effects against ZIKV by specifically...Continue Reading

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Datasets Mentioned

BETA
KY379148.1

Methods Mentioned

BETA
reverse transcription-PCR
PCR
transfection
protein assay
electrophoresis
confocal microscopy
co-IP
immunoprecipitation
co-immunoprecipitation
fluorescence microscopy

Software Mentioned

Quantity One
SPSS

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