The Role of Virus Biological Phenotype in Human Immunodeficiency Virus Pathogenesis

HIV-1 pathogenesis in children as well as in adults is closely associated with changes in co-receptor use of isolated viruses. The ability to use the CXCR4 receptor appears to be a marker of increased virulence, even if the mechanism(s) leading to an accelerated immunodeficiency awaits understanding. Multi-tropism, in the sense that the virus can use several receptors, is not a sign of increased virulence per se, since HIV-2 using many receptors, and presumably entering many different cell types, is less pathogenic than HIV-1. The SIV model is useful in studies of the very early events of virus infection and suggests that the availability of target cells may determine the pattern of co-receptor use.