Correlation of coreceptor usage and disease progression

Primary HIV-1 infection is usually initiated by viruses with an exclusive affinity for the C-C chemokine receptor type 5 (CCR5) coreceptor. Viral variants that are also able to bind the C-X-C chemokine receptor type 4 (CXCR4) coreceptor arise during the course of the disease in about 50% of the infected individuals and their emergence is associated with a faster disease progression. In this article we provide a historical overview of the events that led to the discovery of the relationship between viral phenotype, coreceptor tropism and pathogenesis.

The prevalence of CCR5 and CXCR4-using viruses differs from study to study, but overall percentages of CXCR4 use fluctuate between 2.0 and 63.0%. The association between coreceptor use and disease stage is recognized, with the lowest X4 prevalence in seroconverters and the highest in the final stage of the disease. Up to date there are insufficient arguments to support an impact of coreceptor tropism on response to combined antiretroviral therapy (cART) or an impact of cART on coreceptor tropism evolution.

This review provides an overview of available data on coreceptor use in the different stages of the HIV-1 infection process. Although it is clear that CXCR4-using viruses emerge during the course of infection, the driving forces and mechanisms behind coreceptor switch remain largely unknown.