Enhanced Transmissibility and Decreased Virulence of HIV-1 CRF07_BC May Explain Its Rapid Expansion in China

HIV-1 CRF07_BC is one of the most common circulating recombinant forms (CRFs) in China and is becoming increasingly prevalent especially in HIV-infected men who have sex with men (MSM). The reason why this strain expanded so quickly in China remains to be defined. We previously observed that individuals infected with HIV1 CRF07_BC showed slower disease progression than those infected with HIV-1 subtype B or CRF01_AE. CRF07_BC viruses carry two unique mutations in the p6Gag protein: insertion of PTAPPE sequences downstream of the original Tsg101 binding domain, and deletion of a seven-amino-acid sequence (30PIDKELY36) that partially overlaps with the Alix binding domain. In this study, we confirmed the enhanced transmission capability of CRF07_BC over HIV-1 subtype B or CRF01_AE by constructing HIV-1 transmission networks to quantitatively evaluate the growth rate of transmission clusters of different HIV1 genotypes. We further determined lower virus infectivity and slower replication of CRF07_BC with aforementioned PTAPPE insertion (insPTAP) and/or PIDKELY deletion (D7) in the p6Gag protein, which in turn may increase the pool of people infected with CRF07_BC and the risk of HIV-1 transmission. These new features of CRF07_BC may explain its quick spread and will help adjust prevention strategy of HIV-1 epidemic. IMPORTANCE HIV-1 CRF07_BC is one of the most common circulating recombinant forms (CRFs) in China. The question is why and how CRF07_BC expanded so rapidly remains unknown. To address the question, we explored the transmission capability of CRF07_BC by constructing HIV-1 transmission networks to quantitatively evaluate the growth rate of transmission clusters of different HIV-1 genotypes. We further characterized the role of two unique mutations in CRF07_BC, PTAPPE insertion (insPTAP) and/or PIDKELY deletion (D7) in the p6Gag in virus replication. Our results help define the molecular mechanism regarding the association between the unique mutations and the slower disease progression of CRF07_BC as well as the quick spread of CRF07_BC in China.