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bioRxiv · 10.1101/2020.07.28.226126

Simplexviruses successfully adapt to their host by fine-tuning immune responses

Mozzi, A.·Cagliani, R.·Pontremoli, C.·Forni, D.·Saulle, I.·Saresella, M.·Pozzoli, U.·Clerici, M.·Biasin, M.·Sironi, M.
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Abstract

Primate herpes simplex viruses are relatively harmless to their natural hosts, whereas cross-species transmission can result in severe disease. We performed a genome-wide scan for signals of adaptation of simplexviruses to hominins. We found evidence of positive selection in three glycoproteins, with selected sites located in antigenic determinants. Positively selected non-core proteins were involved in different immune-escape mechanisms. By expressing mutants of one of these proteins (ICP47), we show that the amino acid status at the positively selected sites is sufficient to induce HLA-G. HSV-1/HSV-2 ICP47 induced HLA-G when mutated to recapitulate residues in B virus, whereas the mutated version of B virus ICP47 failed to determine HLA-G expression. Thus, the evolution of ICP47 in HSV-1/HSV-2 determined the loss of an immunosuppressive effect, suggesting that simplexviruses tune immune responses to promote successful co-existence with their hosts. These results also help explain the high pathogenicity of B virus in humans.

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Mozzi, A., Cagliani, R., Pontremoli, C., Forni, D., Saulle, I., Saresella, M., Pozzoli, U., Clerici, M., Biasin, M., Sironi, M.. 2020-07-29. Simplexviruses successfully adapt to their host by fine-tuning immune responses. https://doi.org/10.1101/2020.07.28.226126

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