CCR5tropic

CCR5tropic refers to strains of HIV-1 that primarily use the CCR5 chemokine receptor as a co-receptor for entry into host cells, in contrast to CXCR4-tropic strains that use CXCR4. During early infection, R5-tropic viruses are typically dominant and are common in mucosal transmission; X4-tropic or dual-tropic viruses may appear later in some individuals and can be associated with faster disease progression in some cases.

Mechanism and tropism: HIV-1 entry requires binding of the viral gp120 to CD4 followed by engagement of a co-receptor. R5-tropic viruses interact with CCR5, enabling fusion and infection of CCR5-expressing cells such as activated CD4+ T cells and macrophages. Tropism is determined largely by the envelope, especially the V3 loop, and can evolve over time within a host.

Testing and interpretation: Tropism is assessed with phenotypic assays that test viral growth in the presence of CCR5 inhibitors or with genotypic approaches that predict coreceptor usage from gp120 sequence. Tropism testing is used to determine whether a patient’s virus is likely to respond to CCR5 antagonists and to guide treatment decisions.

Clinical implications and therapy: CCR5 antagonists (for example, maraviroc) are effective only against R5-tropic HIV-1 and require pretreatment tropism testing. If X4-tropic or dual-tropic virus is present, CCR5 antagonists are unlikely to be effective. Tropism can change over time, so ongoing monitoring or repeat testing may be relevant in certain clinical scenarios.

See also: HIV co-receptors, CCR5, CXCR4, viral tropism, CCR5 antagonists.