Naturally Occurring Mutations in HIV-1 CRF01-AE Capsid Affect Viral Sensitivity to Restriction Factors

Abstract

TRIM5α and MxB are known as restriction factors that inhibit the early step of intracellular HIV-1 replication cycle. Both factors are believed to interact with the incoming virus core to suppress HIV-1 infection. The extreme diversity of HIV-1 is thought to be a consequence of its propensity to mutate to escape immune responses and host restriction factors. We recently determined the capsid sequences for 144 HIV-1 CRF01-AE viruses obtained in Thailand from 2005 to 2011. In this study, we further analyzed the amino acid variations among the capsid sequences of 204 HIV-1 CRF01-AE obtained in Thailand and China, including 84 of the aforementioned 144 viruses, to detect mutations permitting escape from restriction by host factors. We found a characteristic combination of E79D, V83T, and H87Q in sequences from Chinese viruses and subsequently showed that this combination conferred partial resistance to MxB. Interestingly, this combination conferred resistance to human TRIM5α as well. The H87Q mutation alone conferred resistance to MxB in the CRF01-AE background, but not in subtype B virus. In contrast, the H87Q mutation alone conferred resistance to human TRIM5α in both the CFR01-AE and subtype B backgrounds. BLAST analysis revealed the presence of the E79D, V83T, and H87Q combination in CRF01-AE viruses isolated not only in China but also in many other countries. Although the mechanistic details as well as precise role of MxB antiviral activity in infected individuals remain to be clarified, our data suggest an interaction between MxB and the HIV-1 capsid in vivo.