Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses

The genetic diversity of HIV impedes vaccine development. Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. Our findings suggest MTF transmission may select viruses with compact envelopes. •We generated infectious molecular clones of HIV-1 subtype C transmitted/founder (T/F) and chronic infection variants.•The HIV-1 subtype C infectious clones display heterogeneity in in vitro replicative capacity and resistance to type I interferon.•T/F clones predominantly use the CCR5 coreceptor; shorter Env variable regions and fewer glycans compared to chronic viruses.