Unique SARS-CoV protein nsp1: bioinformatics, biochemistry and potential effects on virulence

Abstract

Viruses have evolved a myriad of strategies for promoting viral replication, survival and spread. Sequence analysis of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) genome predicts several proteins that are unique to SARS-CoV. The search to understand the high virulence of SARS-CoV compared with related coronaviruses, which cause lesser respiratory illnesses, has recently focused on the unique nsp1 protein of SARS-CoV and suggests evolution of a possible new virulence mechanism in coronaviruses. The SARS-CoV nsp1 protein increases cellular RNA degradation and thus might facilitate SARS-CoV replication or block immune responses.

Figure 1

Potential mechanisms of SARS-CoV nsp1 in virulence. (a) Nsp1 can cause degradation of host RNA (directly or indirectly), thus increasing viral replication. (b) Nsp1 degradation of RNA might decrease the ability of professional antigen presenting cells (APC) to present viral peptides to T cells by decreasing host major histocompatibility complexes (MHC), antigen processing, co-stimulatory molecules or expression of soluble effectors such as cytokines. (c) Nsp1 RNA degradation could block MHC presentation from virally infected cells, decreasing CTL killing.