Upregulation of Noxa and p53 upregulated modulator of apoptosis (PUMA) in response to Zika virus infection

Diksha  Pokhrel; Atitaya  Hitakarun; Sittiruk  Roytrakul; Nitwara  Wikan; Duncan R. Smith

Authors

Diksha Pokhrel Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand
Atitaya Hitakarun Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand
Sittiruk Roytrakul National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathumthani 12120, Thailand
Nitwara Wikan Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand
Duncan R. Smith Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand

Keywords:

Apoptosis, ER-stress, expression of Noxa and PUMA, NOXA, PUMA, Zika virus

Abstract

Zika virus (ZIKV) is a single stranded RNA virus that belongs to the genus Flavivirus, family Flaviviridae. The symptoms associated with ZIKV are normally a mild fever, headache, rash and conjunctivitis, but after 2015, ZIKV became a public health concern worldwide because of the occurrence of microcephaly in newborns from mothers infected with Zika virus during pregnancy. Virus replication inside host cells causes accumulation of disordered proteins, and exploitation of ER membranes can cause ER stress that leads to anti-viral defense mechanisms and cell death. Noxa and p53 upregulated modulator of apoptosis (PUMA) belong to Bcl-2 homology domain (BH3) family and induction of both Noxa and PUMA is mediated through p53 in prolonged ER stress conditions. As a recently emerging virus, little is known about strain specific manifestations of this virus and whether ZIKV associated with cases of microcephaly are functionally distinct from normal circulating virus remains unclear. Therefore, this study aimed to analyze expression of Noxa and PUMA in A549 cells after infection with two different Thai strains of Zika virus, namely SV0010/15 isolated from a Thai case of Zika fever, and MU1-2017 isolated from the brain tissue of a fetus aborted for reasons of abnormal development including microcephaly. Results showed significant increase in expression of Noxa and PUMA in A549 cells infected by both viruses, compared with mock infected cells. This shows that ZIKV infection in A549 cell induces p53 mediated ER stress that may lead to apoptosis.

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