Changes in HIV-1 Capsid Stability Induced by Common Cytotoxic-T-Lymphocyte-Driven Viral Sequence Mutations

Abstract

Sequence mutations within p24 Gag selected by CTL responses restricted by protective HLA class I alleles have been associated with reduced viral fitness. However, the precise mechanisms underlying the reduced viral replication capacity and lower viral loads associated with these mutations remain unclear. Here, we demonstrate that dominant HLA-B27-associated CTL escape mutations within HIV-1 capsid lead to enhanced capsid rigidity, providing a possible mechanism for the reduced viral fitness of these variants.