Zhang and colleagues have verified three molecular determinants of HIV-1 subtype C coreceptor switching. It is the first study of its type to use cloned virus. The topic of coreceptor switching is a hot one! Particularly since the advent of coreceptor inhibiting antiretrovirals, such as Maraviroc (CCR5 antagonist), developing methods of determining HIV tropism in patients has become increasingly important. There are phenotypic methods (ES Trofile), but these are costly and impractical in resource-limited regions, so we are looking for ways to determine tropism using genotypic tools. The three molecular determinants:
(1) Increased positive charge (+6 versus +5) in the V3 loop of env.
(2) MG or LG insertion immediately following position 13.
(3) AA substitution by T downstream of the “GPGQ crown”.
They have indicated that these mutations are required but singularly insufficient to render X4 virus. Knowledge of determinants like these makes it possible to construct algorithms that can decipher tropism directly from genetic information.
Zhang H. et al. Molecular determinants of HIV-1 Subtype C coreceptor transition from R5 to R5X4. Virology. (2010). 407:68-79.