Antigenic diversification is correlated with increased thermostability in a mammalian virus

Abstract

The theory of plastogenetic congruence posits that ultimately, the pressure to maintain function in the face of biomolecular destabilization produces robustness. As temperature goes up so does destabilization. Thus, genetic robustness, defined as phenotypic constancy despite mutation, should correlate with survival during thermal challenge. We tested this hypothesis using vesicular stomatitis virus (VSV). We produced two sets of evolved strains after selection for higher thermostability by either preincubation at 37°C or by incubation at 40°C during infection. These VSV populations became more thermostable and also more fit in the absence of thermal selection, demonstrating an absence of tradeoffs. Eleven out of 12 evolved populations had a fixed, nonsynonymous substitution in the nucleocapsid (N) open reading frame. There was a partial correlation between thermostability and mutational robustness that was observed when the former was measured at 42°C, but not at 37°C. These results are consistent with our earlier work and suggest that the relationship between robustness and thermostability is complex. Surprisingly, many of the thermostable strains also showed increased resistance to monoclonal antibody and polyclonal sera, including sera from natural hosts. These data suggest that evolved thermostability may lead to antigenic diversification and an increased ability to escape immune surveillance in febrile hosts, and potentially to an improved robustness. These relationships have important implications not only in terms of viral pathogenesis, but also for the development of vaccine vectors and oncolytic agents.

A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses

“…The mutational bias of RT may also differ from that of viral RNA-dependent RNA polymerases. Guanine to adenine transitions are the most common mutation made by RT (Gout et al, 2013; Mansky and Temin, 1995; Holtz and Mansky, 2013; Cuevas et al, 2015) and are the ones found most frequently in our study as well as many others that rely on RT-PCR amplification for sequencing (for example, [Crotty et al, 2000; Pauly and Lauring, 2015; Cheung et al, 2014; Presloid et al, 2016]). In contrast, our fluctuation test suggests that A to G and U to C mutations are the most common classes in influenza.…”

Identification of H209 as Essential for pH 8-Triggered Receptor-Independent Syncytium Formation by S Protein of Mouse Hepatitis Virus A59

“…The relationship between the stability of glycoproteins of other types of enveloped viruses and their fitness has been studied extensively (37)(38)(39)(40)(41)(42)(43)(44). The pH stability of influenza virus hemagglutinin (HA) has been linked to differences in host adaptation and transmission.…”

The mutation rates and mutational bias of influenza A virus

“…Guanine to adenine transitions are the most common mutation made by RT (28, 31–33) and are the ones found most frequently in our dataset as well as many others that rely on RT-PCR amplification for sequencing (e.g. (11, 12, 53, 54)). In contrast, our fluctuation test suggests that A to G and U to C mutations are the most common classes in influenza.…”