Selection for thermostability resulted surprisingly in antigenic variation

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Antigenic diversification is correlated with increased thermostability in a mammalian virus


Text by John B. Presloid

Vesicular stomatitis virus (VSV), a model frequently used to study the evolution of RNA viruses, can adapt to survive and replicate at relatively high temperature, so it becomes more thermostable. Some theoretical work suggests that when thermostability increases we can expect a correlated increase in genetic robustness, so the same amount of mutation results in fewer phenotypic changes. Our thermostable strains showed some evidence supporting this correlation between thermosability and robustness, but only in some cases and under specific conditions. However, we did find that thermostable strains tended to accumulate mutations in antigenic sites, which result in antibody escape, which was generally not observed in control populations that had not increased their thermostability.

We addressed these studies as the logical continuation of our interest in the research of quasispecies theory as it applies to viral populations.  In the late 70s and early 80s Esteban Doming and John Holland started applying quasispecies theory, as proposed by Manfred Eigen to explain the early evolution of an RNA world, to RNA virus populations.  Our group has been testing the predictions of quasispecies theory using VSV as a model and demonstrated that selection promotes robustness while drift allows loss of robustness.  We then started testing the predicted correlation between thermostability and robustness looking at viral populations that differed in robustness and found that it is complex and predicting one based on the other is a difficult task.  The next step was to select for thermostability and then look at robustness, which is the topic of our paper.  To select thermostable VSV we used two methods: incubation at high temperature between infections and incubation at higher temperature during the infectious cycles.  Because we measure robustness as resistance to mutagen, we had to test whether our evolved strains had changes their mutation rate, and we did so looking at mutant frequency and, specifically, escape from a monoclonal antibody.  To our surprise, many of the thermostable strains had increased substantially their resistance to antibody, and some had become almost completely resistant.  In contrast, strains evolved under similar conditions, but without the thermal selective pressure (high temperature) , very rarely become resistant.  Once we saw the result for monoclonal antibody we wondered whether this had a wondered applicability and used immune sera from natural hosts (pigs and horse) and a laboratory host (rabbit) to confirm that this is the case.

Figure 1

Figure legend

Schematic for experimental evolution. Regimens used to generated the 37-adapted and 40-adapted populations as well as the adapted controls.

Introducing the author


Pictured: John B. Presloid

About the research

Antigenic diversification is correlated with increased thermostability in a mammalian virus
John B. Presloid, Tasneem F. Mohammad, Adam S. Lauring, Isabel S. Novella
Virology, Volume 496, September 2016, Pages 203–214