Are subtype-C viruses of HIV-1 the fittest?
The HIV-AIDS laboratory at JNCASR, Bangalore is one of the few in India dedicated for HIV research. Our focus is on the characterization of the biological and molecular properties of the subtype-C viruses with special emphasis on how these differences at the biological level might influence their pathogenic properties. HIV-1 is classified into several genetic subtypes or clades that are designated A through K. Of these various genetic families, subtype-C viruses alone are responsible for nearly half of the infections in the world and almost 99% of infections in India. Are subtype-C viruses endowed with unique biological properties that make them successful in establishing the rapidly spreading epidemics of the world? We are preoccupied with finding an answer to this important question. Ours is a well-equipped, self-sufficient and dedicated BSL II plus facility for handling the viral culture. The laboratory has active research collaborations with several hospitals, NGOs and academic laboratories on the national and international scale.
Current areas of research:
· Molecular evolution and molecular biology of HIV-1 subtypes
· Immunoactivation in HIV-AIDS
· Host immune response to HIV-1 and chronic immune activation
· DNA vaccine engineering and optimization
· HIV-1 broadly neutralizing antibodies
Focus of the laboratory:
The fascination of our laboratory is with HIV-1 subtype-C. Consider the following facts, you will understand why.
1. Of the various HIV-1 genetic subtypes, subtype-C alone is responsible for half of the global HIV-1 infections. What makes subtype-C the ‘super HIV’? Its milder (attenuated) nature? This assumption is highly controversial.
2. In India, subtype-C viral strains are responsible for nearly 99% of the infections.
3. Subtype-C global prevalence increased over the past decades from 25% to nearly 50% today.
4. In countries (eg. India and South Africa) where subtype-C is the founder virus (the first one to appear), other subtypes do not seem capable of setting a foothold. No recombinants appear or dominate in these locations. In countries where other subtypes are prevalent, subtype-C produces recombinants and the recombinants appear to quickly dominate the epidemics (eg. China and Brazil).
5. The bulk of the published research is HIV-1 subtype-B centric. We do not know if other subtypes too differ in biological properties. For instance, could subtype-C be less pathogenic as compared to subtype-B?
6. Subtype-C demonstrates important phenotypic properties that are independent of host factor differences such as the co-receptor preference for infection. Unlike other HIV-1 subtypes, subtype-C does not switch its co-receptor usage from CCR5 to CXCR4. It is not clear why the co-receptor switch is necessary for other subtypes, but not for subtype-C. What is the biological significance of this difference? Likewise, we demonstrated that the duplication of the NF-κB motifs in the viral promoter is an exclusive property of subtype-C. All the viral subtypes, including subtype-C, can duplicate the adjacent RBEIII site, but only subtype-C can duplicate the NF-κB sites. The molecular mechanism that governs this phenomenon is presently being investigated.
Some Questions We Would Like To Address:
1.What makes viral subtypes different?
· Subtypes differ up to 35% at the genetic level in some genes such as env. Can genetic variation to this extent translate to biological differences?
· Why subtype C is causing half of the global infections?
· Why only a small minority of viral recombinants survives?
2. Where is HIV heading?
· Is HIV evolving? (Reduced pathogenicity???)
· Which evolutionary path the virus is likely to take?
· Can we predict viral fitness value?