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 (CD8 TL )-mediated escape, but their impact on viral evolution following transmission to naive hosts remains unclear. Here, we investigated the reversion kinetics of Gag 181–189 CM9 CD8 TL 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 Gag 181–189 CM9 escape mutations. Therefore, transmitted compensatory mutations do not necessarily predict rapid CD8 TL escape.