Background: Viral evolution of HIV-1 is dynamic and moving towards a higher order of replicative fitness. Results: HIV-1 subtype C acquires an extra (4th) NF-B site to achieve a higher degree of transcription and in turn enhances its replicative fitness and preponderance. Conclusion: Subtype C with an extra NF-B site adopts a novel strategy of strengthening its promoter to gain fitness. Significance: Learning how the new strains could impact viral prevalence, pathogenesis, and disease management strategies is critical.
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-jB and RBEIII, importantly, in a mutually exclusive fashion. Furthermore, while some of the viral strains contained insertions of jB-like sites, a few others contained dual insertions of the RBEIII and jB sites together but only one of the two was intact. NFjB 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-jB sites in the viral enhancer, acquisition of a fourth NF-jB 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.
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