HIV coreceptors, cell tropism and inhibition by chemokine receptor ligands

HIV is a persistent virus that survives and replicates despite an onslaught by the host's immune system. A strategy for cell entry, requiring the use of two receptors, has evolved that may help evade neutralizing antibodies. HIV and SIV usually require both CD4 and a seven transmembrane (7TM) corece ptor for infection. At least eleven different 7TM coreceptors have been ide ntified that confer HIV and/or SIV entry. For HIV-1, the major coreceptors are CCR5 and CXCR4, while the role of other coreceptors for replication and cell tropism in vivo is currently unclear. Polymorphisms in the CCR5 gene that reduce CCR5 expression levels, protect against disease progression, su ggesting that drugs targeted to CCR5 could be effective. Such therapies how ever will not work if HIV simply adapts to use alternative coreceptors. In the light of these themes, this review will discuss the following topics: ( i) the coreceptors used by primary HIV-1 and HIV-2 viruses, (ii) the proper ties and coreceptors of HIV-2 strains that infect cells without CD4, (iii) the role of coreceptors in HIV cell tropism and particularly macrophage inf ection and (iv) the properties of chemokine receptor ligands that block HIV infection.