Molecular identification, cloning and characterization of transmitted/founder HIV-1 subtype A, D and A/D infectious molecular clones.
Baalwa J., Wang S., Parrish NF., Decker JM., Keele BF., Learn GH., Yue L., Ruzagira E., Ssemwanga D., Kamali A., Amornkul PN., Price MA., Kappes JC., Karita E., Kaleebu P., Sanders E., Gilmour J., Allen S., Hunter E., Montefiori DC., Haynes BF., Cormier E., Hahn BH., Shaw GM.
We report the molecular identification, cloning and initial biological characterization of 12 full-length HIV-1 subtype A, D and A/D recombinant transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open reading frames and all T/F viruses were replication competent in primary human T-cells, although subtype D virus replication was more efficient (p<0.05). All 12 viruses utilized CCR5 but not CXCR4 as a co-receptor for entry and exhibited a neutralization profile typical of tier 2 primary virus strains, with significant differences observed between subtype A and D viruses with respect to sensitivity to monoclonal antibodies VRC01, PG9 and PG16 and polyclonal subtype C anti-HIV IgG (p<0.05 for each). The present report doubles the number of T/F HIV-1 clones available for pathogenesis and vaccine research and extends their representation to include subtypes A, B, C and D.