Tertiary Mutations Stabilize CD8+ T Lymphocyte Escape-Associated Compensatory Mutations following Transmission of Simian Immunodeficiency Virus

ABSTRACT Compensatory mutations offset fitness defects resulting from CD8+ T lymphocyte (CD8TL)-mediated escape, but their impact on viral evolution following transmission to naive hosts remains unclear. Here, we investigated the reversion kinetics of Gag181–189CM9 CD8TL escape-associated compensatory mutations in simian immunodeficiency virus (SIV)-infected macaques. Preexisting compensatory mutations did not result in acute-phase escape of the SIVmac239 CD8TL epitope Gag181-189CM9 and instead required a tertiary mutation for stabilization in the absence of Gag181–189CM9 escape mutations. Therefore, transmitted compensatory mutations do not necessarily predict rapid CD8TL escape.

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