Speaker
Description
Introduction: A single virus termed HIV-1 Transmitted/Founder (T/F) virus establishes productive clinical infection in 80% of heterosexual cases. The genetic signatures in the envelope glycoprotein (Env) of HIV-T/F subtypes B and C viruses are linked to transmission fitness. However, there is limited evidence on the unique genetic signatures in the Env of HIV-1 T/F subtypes A1, D and A1/D recombinants predominant in Uganda and East Africa. Methodology: Full-length HIV-1 T/F Env subtype A1 sequences (N=41) were generated from acutely infected individuals using Single genome amplification and oxford nanopore sequencing. The phylogenetically corrected strategies (Gensig and Entropy tools) detected the unique genetic signatures in HIV-1 Env associated to the subtype A1 T/F (N=41) compared to the chronic sequences (N=67) (P < 0.01, FDR < 0.2, fisher’s test). Results: The HIV-1 T/F clade A1 Envs exhibited higher genetic variation than the chronics. The Tryptophan signature was more enriched at position 11 in the signal peptide of clade A1 T/F Envs than the clade A1 chronics. The Aspartate was more enriched at position 133 in the V1 loop and VRC38.01 contact site; and Lysine enriched at position 290 in clade A1 chronics than clade A1 T/F gp120 domain. Arginine at position 335 was more associated with clade A1 chronics compared to clade A1 T/F gp120. The HIV-1 T/F clade A1 Envs appeared less glycosylated than the chronics in the V5 hypervariable region, HXB2 Positions: 460-465 (P-value = 0.01083). Conclusion: Additional analyses will detect unique genetic signatures in subtypes D and A1D recombinants as well as 3D signature mapping of these sites. The unique genetic signatures will be associated with bNAbs. These findings are relevant to informing therapeutic strategies targeting genetic signatures selected during acute HIV infection. As well as recurrent signature patterns evading immune responses in the chronic phase of infection.
