Antiviral Activity of Human Immunodeficiency Virus Type 1 Gag-Specific Cytotoxic T Lymphocyte Targeting Is Not Necessarily Intrinsically Superior to Envelope Targeting

Across several cohorts, human immunodeficiency virus type 1 (HIV-1) Gag-and Env-specific CD8(+) T lymphocyte (CTL) responses have demonstrated inverse and positive correlations, respectively, to viremia. The mechanism has been proposed to be superior antiviral activity of Gag-specific CTLs in general. Addressing this hypothesis, we created two HIV-1 constructs with an epitope translocated from Gag (SLYNTVATL, SL9) to Env, thereby switching the protein source of the epitope. A virus expressing SL9 in Env was similar to the original virus in susceptibility to SL9-specific CTLS. This finding suggests that Env targeting is not intrinsically inferior to Gag targeting for CTL antiviral activity.