Rapid Progression to AIDS in HIV ⁺ Individuals with a Structural Variant of the Chemokine Receptor CX ₃ CR1

Abstract

Human immunodeficiency virus (HIV) enters cells in vitro via CD4 and a coreceptor. Which of 15 known coreceptors are important in vivo is poorly defined but may be inferred from disease-modifying mutations, as for CCR5. Here two single nucleotide polymorphisms are described in Caucasians in CX3CR1, an HIV coreceptor and leukocyte chemotactic/adhesion receptor for the chemokine fractalkine. HIV-infected patients homozygous for CX3CR1-I249 M280, a variant haplotype affecting two amino acids (isoleucine-249 and methionine-280), progressed to AIDS more rapidly than those with other haplotypes. Functional CX3CR1 analysis showed that fractalkine binding is reduced among patients homozygous for this particular haplotype. Thus, CX3CR1-I249 M280 is a recessive genetic risk factor in HIV/AIDS.

Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity

“…Previous studies have identified genetic polymorphisms in chemokine receptor genes that encode molecules critical for HIV-1 entry into host cells (30,(33)(34)(35). Other studies have identified independent HLA associations with susceptibility or resistance to HIV-1 disease progression after infection with the virus has occurred.…”

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis

“…They affect susceptibility or resistance to several infectious diseases. 45,46,[61][62][63][64] In addition, chemokine receptor signaling processes are important for leukocyte recruitment and controlled trophoblast invasion and thus for implantation and placentation. 25,26 CCR2 and CCR5 are chemokine receptors that have been assigned a function in toxoplasmosis and, independently in pregnancy, they protect from uncontrolled T. gondii replication in adults and favor trophoblast survival or invasion (related to a Th1 response), partially explaining the first-trimester resistance against vertical transmission.…”

A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case–control and a family study in Tunisia

“…19 Real-time detection and analyses were performed on an ABI 7700 thermocycler (Applied Biosystems).…”

“…We identified two common single-nucleotide polymorphisms (SNPs), known as V249I and T280M, in the open reading frame of the chemokine receptor CX3CR1 gene. 19 The common CX3CR1-I249 allele and its genetically linked partner, the CX3CR1-M280 allele, are associated with a reduced risk of cardiovascular diseases 20,21 and inflammatory lung disorders. 22,23 CX3CR1 is thus another plausible link between inflammation, airway remodelling and asthma.…”