Tertiary mutations stabilize CD8+ T lymphocyte escape-associated compensatory mutations following transmission of simian immunodeficiency virus.

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.