Clinical isolates of primate immunodeficiency viruses, including human immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor CCR5, a member of the seven-transmembrane receptor family. HIV-1 variants which use additional chemokine receptors are present in the central nervous system or emerge during the course of infection. Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a coreceptor, but no other receptors for these viruses have been identified. 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. The more efficient of these, gpr15, is also expressed in human CD4+ T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues. These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis.

Background While some individual foods and nutrients have been associated with knee osteoarthritis (KOA) progression, the association between dietary patterns and KOA progression has received little research attention. Objective The objective of this study was to determine whether dietary patterns, derived by principal components analysis (PCA), are associated with KOA progression. Methods In the Osteoarthritis Initiative (OAI), a prospective cohort with clinical centers in Maryland, Ohio, Pennsylvania, and Rhode Island, 2757 participants with existing KOA (mean age 62 y) and diet assessed at baseline were followed for ≤72 mo. Using PCA, Western and prudent dietary patterns were derived. Radiographic KOA progression was assessed using 2 separate measures, 1 full Kellgren–Lawrence (KL) grade increase and loss in joint space width (JSW). Symptomatic KOA progression was defined as an increase in or remaining in 1 of the 2 highest classification categories of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Results Adherence to Western and prudent dietary patterns was significantly associated with radiographic and symptomatic progression of KOA. With increasing Western pattern score, there was increased KL-worsening risk (compared with quartile 1, HR for quartile 4: 1.30; 95% CI: 1.05, 1.61; P-trend < 0.01) and increased odds of progression to higher WOMAC score (compared with quartile 1, OR for quartile 4: 1.39; 95% CI: 1.18, 1.63; P-trend < 0.01) but no significant change in JSW loss. With increasing prudent pattern score there was decreased KL-worsening risk (compared with quartile 1, HR for quartile 4: 0.79; 95% CI: 0.64, 0.98; P-trend = 0.02), decreased JSW loss (quartile 1: 0.46 mm; quartile 4: 0.38 mm; P-trend < 0.01), and decreased odds of higher WOMAC progression (compared with quartile 1, OR for quartile 4 0.73; 95% CI: 0.62, 0.86; P-trend < 0.01) in multivariable adjusted models. Conclusions Adherence to a Western dietary pattern was associated with increased radiographic and symptomatic KOA progression, while following a prudent pattern was associated with reduced progression. In general, for people already diagnosed with KOA, eating a diet rich in fruits, vegetables, fish, whole grains, and legumes may be related to decreased radiographic and symptomatic disease progression.