Antigenic diversification is correlated with increased thermostability in a mammalian virus
| Autor: | John B. Presloid, Adam S. Lauring, Isabel S. Novella, Tasneem F. Mohammad |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Nonsynonymous substitution Viral pathogenesis Adaptation Biological Biology Virus Article 03 medical and health sciences Virology Antigenic variation Animals Humans Thermostability Genetics Temperature Robustness (evolution) biology.organism_classification Adaptation Physiological Antigenic Variation Biological Evolution Oncolytic virus 030104 developmental biology Amino Acid Substitution Vesicular stomatitis virus Mutation Viruses |
| Zdroj: | Virology. 496:203-214 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2016.06.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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