Inherited Resistance to HIV-1 Conferred by an Inactivating Mutation in CC Chemokine Receptor 5: Studies in Populations with Contrasting Clinical Phenotypes, Defined Racial Background, and Quantified Risk

Abstract

The data suggest that homozygous CCR5-2 is an HIV-1 resistance factor in Caucasians with complete penetrance, and that heterozygous CCR5-2 slows the rate of disease progression in infected Caucasian homosexuals. Since the majority (approximately 96%) of highly exposed-seronegative individuals tested are not homozygous for CCR5-2, other resistance factors must exist. Since CCR5-2 homozygotes have no obvious clinical problems, CCR5 may be a good target for the development of novel antiretroviral therapy.

CCR5-Δ32 mutation is strongly associated with primary sclerosing cholangitis

“…In addition, the control allele frequency was consistent with previous studies from Caucasian populations. 24 Importantly, the PSC cohort in this study was particularly well characterized. Relevant and detailed clinical information was available for over 90% of the patients and, specifically, the diagnosis of PSC was based on both radiological and histological records for all patients included in the study.…”

“…21 CCR5 is a coreceptor for the M-tropic strain of human immunodeficiency virus (HIV) and as a result CCR5-D32 homozygotes are afforded complete immunity from this strain, while heterozygotes show resistance to infection and a delay in the onset of acquired immunodeficiency syndrome (AIDS) compared to the wild-type counterparts. [22][23][24][25] In chronic inflammatory disorders, the CCR5-D32 mutation shows a negative association with rheumatoid arthritis, 26 which in turn is associated with a predominantly Th1 immune response. In patients with multiple sclerosis, the mutation is associated with a delayed age of onset of the disease and a lower risk of recurrent clinical disease activity.…”

Lentiviral transduction of human T-lymphocytes with a RANTES intrakine inhibits human immunodeficiency virus type 1 infection

“…1,2 Persons with a homozygous 32 base-pair deletion in the CCR-5 gene, resulting in a truncated protein that remains within the cell, are highly resistant to HIV-1 infection. [9][10][11][12][13][14] This alteration does not affect the health of homozygous carriers, indicating that its functions are dispensable. [9][10][11][12][13][14] Thus, CCR-5 affords an attractive therapeutic target, especially for patients in the early stage of infection.…”

The Distribution of CCR2-64I, SDF1-3′A and MCP1-2518 G/A Genes Polymorphism in a Specific High Risk Group from the Northeastern States West Bengal, and Gorkha Population in India

“…Chemokine receptors such as CCR5 and CXCR4 are known to be associated with entry of HIV into susceptible cells like T lymphocytes, macrophages and Langerhan's cell [13,16,30]. Primarily, the macrophage line viruses also called the Non syncitium inducing (NSI) strains or R5 viruses utilize the CCR5 receptors whereas the T cell line viruses also known as the Syncitium inducing (SI) strains or X4 viruses use the CXCR4 receptors for entry into the cell [6,[9][10][11].…”