The coreceptor usage of an HIV strain (CCR5 vs. CXCR4) largely defines its cytopathology, replication kinetics, and tissue tropism in in vitro culture. CXCR4-using (X4) isolates tend to replicate rapidly, induce the formation of syncitia (giant multinucleated cells), and have the capacity to infect transformed T cell lines. CCR5-using (R5) isolates, on the other hand, replicate slowly, do not induce syncytia, and can often infect monocyte-derived macrophages in a laboratory setting (Fenyo et al, 1997).
Coreceptor usage is also indicative of in vivo pathogenicity and transmissibility. CXCR4 strains are associated with more rapid progression to AIDS, in line with their accelerated replication rates in vitro (Kreisberg et al, 2001). It has been observed that HIV-infected individuals experiencing opportunistic infections associated with end-stage disease are several times more likely to harbor a syncitium-inducing (X4) strain than asymptomatic patients (Richman et al, 1994). In addition, people homozygous for a common 32 base-pair deletion in the gene encoding the CCR5 receptor may only be productively infected by CXCR4-using HIV variants (Michael et al, 1998). Coreceptor usage also modulates viral access to various compartments within the human body, due to tissue-specific cellular characteristics. For example, HIV infection in the central nervous system is highly correlated with the preferential usage of CCR5, while the thymus is mainly colonized by X4 variants (Shieh et al, 1998;Kitchen et al, 1997). In light of the AIDS epidemic as a whole, the majority of HIV-positive individuals are initially infected with R5 HIV strains, suggesting that there may be a selective advantage of such variants with respect to transmission (van't Wout et al, 1994).
In all, the coreceptor used by a particular HIV strain is highly indicative of its behavior both in in vitro and in vivo settings. Unsurprisingly, the determination of this viral phenotype is critical in a wide variety of HIV research contexts. Coreceptor usage is typically determined by either laboratory-based assay or amino acid sequence-based prediction. If you have sequences to screen, you can go back and scroll down to try out several of our classifiers.