HIVbio: HIV Bioinformatics |
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HIV TropismHIV tropism refers to the cell type that the human immunodeficiency virus (HIV) infects and replicates in. HIV tropism of a patient's virus is measured by the Trofile assay.HIV can infect a variety of cells such as CD4+ helper T-cells and macrophages that express the CD4 molecule on their surface. HIV-1 entry to macrophages and T helper cells is mediated not only through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells but also with its chemokine coreceptors. Macrophage (M-tropic) strains of HIV-1, or non-syncitia-inducing strains (NSI) use the beta-chemokine receptor CCR5 for entry and are thus able to replicate in macrophages and CD4+ T-cells. The normal ligands for this receptor, RANTES, macrophage inflammatory protein (MIP)-1-beta and MIP-1-alpha, are able to suppress HIV-1 infection in vitro. This CCR5 coreceptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype. T-tropic isolates, or syncitia-inducing (SI) strains replicate in primary CD4+ T-cells as well as in macrophages and use the alpha-chemokine receptor, CXCR4, for entry. The alpha-chemokine, SDF-1, a ligand for CXCR4, suppresses replication of T-tropic HIV-1 isolates. It does this by down regulating the expression of CXCR4 on the surface of these cells. Viruses that use only the CCR5 receptor are termed R5, those that only use CXCR4 are termed X4, and those that use both, X4R5. However, the use of coreceptor alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection. HIV can also infect a subtype of dendritic cells, MDC-1, which probably constitute a major reservoir that maintains infection when T helper cell numbers have declined to extremely low levels. Delta-32Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection HIV-1 infection in individuals with the CCR5-Delta32/Delta32 genotype: acquisition of syncytium-inducing virus at seroconversion Reappraisal of the historical selective pressures for the CCR5-32 mutation Persistence of dual-tropic HIV-1 in an individual homozygous for the CCR532 allele Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation |