Three adjacent nucleotide changes spanning two residues in SARS-CoV-2 nucleoprotein: possible homologous recombination from the transcription-regulating sequence

Shay Leary; Silvana Gaudieri; Abha Chopra; Suman Pakala; Eric Alves; Mina John; Suman Das; Simon Mallal; Phillips Jane Phillips

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.10.029454 doi: bioRxiv preprint However, the fact that a number of variants are established in the human pandemic indicates some capacity for successful viral diversification in response to host immunogenetic heterogeneity. The consequences of viral host adaptation for SARS-CoV-2 immunopathogenesis may also be complex. If SARS-CoV-2 T-cell responses define the specific nature of the clinical illness, such adaptation may serve to favor prolonged, perhaps asymptomatic viral shedding. This phenomena has been demonstrated in the case of mutations in the influenza genome, with deleterious public health consequences for transmission and control 15 . If the host response to SARS-CoV-2 is dependent on the efficacy or regulation of a specific antiviral cytotoxic T-cell response, adaptation may also impact individual pathways to serious complications such as acute respiratory distress syndrome and other end-organ disease. However, it is important to realize that as evidenced by HCV, HIV and other RNA viruses, any change in replicative fitness cost to the virus will not predictably translate to any attenuation of the nature of the disease in the host. As SARS-CoV-2 becomes globally established over a longer period of time, evolution towards a less immunogenic, but still highly transmissible infection could be facilitated by fixation and spread of immune-based selection events. This has been postulated to be the case for other human-adapted coronaviruses that eventually became established as seasonal "common cold" viruses.