Sequence Insertions in the HIV Type 1 Subtype C Viral Promoter Predominantly Generate an Additional NF-κB Binding Site

After screening a large number of clinical samples of HIV-1 subtype C in India, a subset of viral strains containing sequence insertions upstream of the viral enhancer has been identified. The sequence insertions contained binding sites for at least two different transcription factors NF-kappa B and RBEIII, importantly, in a mutually exclusive fashion. Furthermore, while some of the viral strains contained insertions of kappa B-like sites, a few others contained dual insertions of the RBEIII and kappa B sites together but only one of the two was intact. NF-kappa B acquisition appears to be the most common phenotype unique for subtype C with nearly half of the variant strains containing such insertions. Given that subtype C already contains three functional NF-kappa B sites in the viral enhancer, acquisition of a fourth NF-kappa B motif in some variant viral strains is intriguing. Further investigation is warranted to examine the significance of the sequence insertions for the replicative fitness of the variant viral strains.