PARP-1 mediated cell death is directly activated by ZIKV infection

Abstract

Zika virus (ZIKV) has emerged as a severe health threat due to its association with microcephaly. It has been reported that the strong cytopathic effects, including cell-cycle arrest and cell death are responsible for the nervous system disease. However, the mechanisms by which ZIKV infection induced cell death were largely unknown. Here, we reported that cell death is readily detected after ZIKV infection as indicated by PI staining and the reduction of cell viability. Importantly, cell death can be induced by overexpression of ZIKV NS3 protein alone but not the other non-structure proteins. Mass spectrometry analysis revealed that NS3 bond to and activated PARP-1. In agreement with these observations, we found that PARP-1 was massively activated during ZIKV infection and the intracellular ATP and NAD⁺ concentrations rapidly declined. Finally, PARP-1 knockdown simultaneously restrained ZIKV infection-induced cell death and ablated host restriction of virus infection. Our finding indicates that PARP-1 activation is an important cellular event during ZIKV infection, which contributes to the cell death.

Keywords: NAD(+); NS3; PARP-1; Programmed cell death; Zika virus.