Disease relevance of GPR15

• CCR5, GPR15, and CXCR6 are major coreceptors of human immunodeficiency virus type 2 variants isolated from individuals with and without plasma viremia [1].
• HIV-2 isolates from aviremic individuals commonly use as coreceptors CCR5, GPR15, and CXCR6, as well as an unidentified receptor expressed by U87 cells [1].
• The majority of HIV-1 envelopes mediated entry into BOB/GPR15-expressing cells, albeit often with low efficiency [2].
• Use of GPR1, GPR15, and STRL33 as coreceptors by diverse human immunodeficiency virus type 1 and simian immunodeficiency virus envelope proteins [3].

High impact information on GPR15

• Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages [4].
• The more efficient of these, gpr15, is also expressed in human CD4(+) T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells [4].
• Human-derived STRL33 (BONZO) and human-derived GPR-15 (BOB) are also used, but with variable efficiency [5].
• Eleven of sixteen substitutions disrupted entry via CCR5 or the alternative coreceptor GPR15 [6].
• Our data show that some HIV-1 isolates of different genetic subtype and of different biological phenotype use BOB/GPR15 for productive infection and suggest that this cofactor may play a role in HIV-1 pathogenesis and transmission [2].

Chemical compound and disease context of GPR15

• The virotoxin model of HIV-1 enteropathy: involvement of GPR15/Bob and galactosylceramide in the cytopathic effects induced by HIV-1 gp120 in the HT-29-D4 intestinal cell line [7].

Biological context of GPR15

• Taken together, our results indicate that GPR15 and STRL33 are rarely used by HIV-1 but are more frequently used by SIV strains, although not in a manner that correlates with SIV tropism [3].
• This study shows that a single amino acid substitution in the V3 loop of the pathogenic SIVmac239 clone, 321P-->S, impaired the ability to use BOB/GPR15 for entry and replication but had little effect on the ability to use CCR5 [8].
• GPR15 was mapped to human chromosome 3q11.2-q13.1 [9].
• A novel human gene encoding a G-protein-coupled receptor (GPR15) is located on chromosome 3 [9].

Anatomical context of GPR15

• Nevertheless, most of these variants replicated in the macaque T-cell line 221-89 and some also replicated in rhesus macaque peripheral blood monocytes, suggesting that efficient usage of CCR5 and GPR15 on cell lines is not a prerequisite for SIV replication in primary cells [6].

Other interactions of GPR15

• The sequence of three cynomolgus macaque receptors, CCR3, GPR15, and STRL33, are presented in this sequence note [10].
• Neutralizing antibodies to GPR15/Bob but not to CXCR4 (the coreceptor allowing infection with these HIV strains) inhibited these effects [7].

Analytical, diagnostic and therapeutic context of GPR15

• Using primers based on conserved regions of the opioid-related receptors, we isolated a PCR product that was used to locate the full-length coding region of a novel human receptor gene, which we have named GPR15 [9].

References