PARP1 and Viral infection
Several members of PARP family are reported to play varied roles in viral infections. PARP activity or PARylation can function as both enhancer and repressor of virus replication (Ko et al., 2013; Lupey-Green et al., 2017). PARP7, 10 and 12 reportedly inhibits replication of Venezuelan equine encephalitis virus (VEEV) (Atasheva et al., 2012; Atasheva et al., 2014). PARP1 is observed to be a facilitator of influenza A virus (IAV) infection through regulation of RNA dependent RNA polymerase (Rdrp polymerase) of influenza A virus. However, endogenous PARylation inhibited Rdrp assembly (Westera et al., 2019). Host protein PARP1 is reported to facilitate propagation of influenza A virus through degradation of interferon receptor type I (IFNAR) (Xia et al., 2020). This novel role of PARP1 could be utilized to design antivirals for influenza treatment and such study can also be expanded to other viruses which utilizes same receptor for entry in host. Furthermore, PARP1 is required for HIV-1 infection and integration in cells(Ha et al., 2001) and PARP1 activity is also required for transcriptional activation of HIV-1(Yu et al., 2018) . In addition to aforementioned studies, PARP1 inhibition has been found to be effective in management of HIV infection and replication in vitro (Rom et al., 2015). Although some contradictory reports are also there in context to HIV-1 infection but still PARP1 inhibition can be an effective strategy for viral disease management. Recent study has proposed the role of PARP1 in regulating the NK cell migration to the site of viral infection through production of CCL2 and further CCL2-CCR axis regulates the migration of NK cells (Shou et al., 2019). Another instance where interaction with PARP1 was found important for viral biology was Porcine reproductive and respiratory syndrome virus (PRRSV) (Liu et al., 2015), indicating that targeting PARP1 could be a viable option to inhibit virus proliferation.
Interestingly, few studies have recently been carried out to identify PARPs relationship with coronavirus infection and replication in mammalian cells. ADP-ribosylation of coronavirus nucleocapsid protein (N protein) was identified as a novel post translational modification (Grunewald et al., 2018). Several family of virus including Coronaviridae possess a macrodomain with poly(ADP-ribose) glycohydrolase activity. There are reports of a coronavirus macrodomain binding to ADP-ribose and further removal of mono ADP-ribose from proteins thus facilitates virus to replicate. These macrodomains are reported to counteract the antiviral ADP-ribosylation of PARP during infection. Although it has not been clear whether PARP1 is involved in inhibition of coronavirus replication but role of PARP-12 and -14 has been identified in enhancement of interferon production and coronavirus inhibition (Grunewald et al., 2019). Thus, PARP either promotes or inhibits the replication of viruses and their pathogenesis (Fehr et al., 2020). Further analysis of macrodomain of SARS-CoV-2 could highlight the use of PARP inhibitors for treatment of Covid-19.Interestingly, few studies have recently been carried out to identify PARPs relationship with coronavirus infection and replication in mammalian cells. ADP-ribosylation of coronavirus nucleocapsid protein (N protein) was identified as a novel post translational modification (Grunewald et al., 2018). Several family of virus including Coronaviridae possess a macrodomain with poly(ADP-ribose) glycohydrolase activity. There are reports of a coronavirus macrodomain binding to ADP-ribose and further removal of mono ADP-ribose from proteins thus facilitates virus to replicate. These macrodomains are reported to counteract the antiviral ADP-ribosylation of PARP during infection. Although it has not been clear whether PARP1 is involved in inhibition of coronavirus replication but role of PARP-12 and -14 has been identified in enhancement of interferon production and coronavirus inhibition (Grunewald et al., 2019). Thus, PARP either promotes or inhibits the replication of viruses and their pathogenesis (Fehr et al., 2020). Further analysis of macrodomain of SARS-CoV-2 could highlight the use of PARP inhibitors for treatment of Covid-19.