Host shutoff activity of VHS and SOX-like proteins: role in viral survival and immune evasion

Abstract

Background: Host shutoff refers to the widespread downregulation of host gene expression and has emerged as a key process that facilitates the reallocation of cellular resources for viral replication and evasion of host antiviral immune responses. Main body: The Herpesviridae family uses a number of proteins that are responsible for host shutoff by directly targeting messenger RNA (mRNA), including virion host shutoff (VHS) protein and the immediate-early regulatory protein ICP27 of herpes simplex virus types 1 (HSV-1) and the SOX (shutoff and exonuclease) protein and its homologs in Gammaherpesvirinae subfamilies, although these proteins are not homologous. In this review, we highlight evidence that host shutoff is promoted by the VHS, ICP27 and SOX-like proteins and that they also contribute to immune evasion. Conclusions: Further studies regarding the host shutoff proteins will not only contribute to provide new insights into the viral replication, expression and host immune evasion process, but also provide new molecular targets for the development of antiviral drugs and therapies.

The m 6 A reader YTHDC2 is essential for escape from KSHV SOX-induced RNA decay

“…Herpesviruses extensively manipulate the fate of host transcripts during lytic reactivation through the use of virally encoded endonucleases. In the case of KSHV, the viral endonuclease SOX targets a wide array of mRNAs via a sequence-specific degron and cleaves around 70% of mRNAs in the cell ( 1 , 49 , 50 ). This allows the virus unfettered access to the host expression machinery for viral replication.…”

The m6A reader YTHDC2 is essential for escape from KSHV SOX-induced RNA decay

“…Herpesviruses extensively manipulate the fate of host transcripts during lytic reactivation through the use of virally encoded endonucleases. In the case of KSHV, the viral endonuclease SOX targets a wide array of mRNAs via a sequence specific degron and cleaves around 70% of mRNAs in the cell [1, 48, 49]. This allows the virus unfettered access to the host expression machinery for viral replication.…”

Interplay Between CMGC Kinases Targeting SR Proteins and Viral Replication: Splicing and Beyond

“…It is important to note that the impact of HSV-1 infection on cellular splicing and polyadenylation is likely not a complete inhibition. Indeed, changes in alternative polyadenylation and alternative splicing have been documented and some of these alterations may turn out as important to insure a productive infection and immune evasion (Hu et al, 2016;Wang et al, 2016;Tang et al, 2019;He et al, 2020). Homologues of ICP27 displaying similar functions are found in all the other members of the herpes virus family.…”