Abstract 1019 Poster Session IV, Tuesday, 5/4 (poster 107)

Background: Significant cardiac morbidity associated with human immunodeficiency virus (HIV) is estimated at 6-7% and mortality between 1-6%. Cardiomyopathy occurs in about 15% of HIV infected individuals but its pathogenesis is unclear. Recent reports have shown increasing evidence of cardiomyocyte infection by HIV, suggesting that viral mechanisms could play a direct role in the etiology of HIV related cardiac disease. As heart tissue lacks CD4, alternative cellular receptors must be used by HIV to infect the myocardium in a CD4-independent manner. HIV-1 and HIV-2 infection of CD4-negative cells has been shown to occur by means of coreceptor usage. Thus, we examined chemokine (CK) receptor expression in cultured human cardiac myocytes from fetal hearts.

Methods: Expression of the CK receptors CXCR4 and CCR5 was studied in a primary culture of human fetal cardiac myocytes (HFCM) using three different techniques: flow cytometry (FC), indirect immunofluorescence labeling (IF) and a multiprobe ribonuclease protection assay (RPA). Expression of other CK and orphan receptors (e.g. CCR3, CCR8 and gpr1, gpr15 respectively) was also examined by RPA.

Results: FC analysis showed that 26% of HFCM expressed CXCR4. Expression of CXCR4 was also detected by IF and RPA. Interestingly, expression of gpr1, implicated as a coreceptor for simian immunodeficiency virus infection, was also identified by RPA. In contrast, no evidence of CCR5 expression was observed by FC or by RPA. Similarly, RNA for other CK receptors, CCR3, CCR2b and CCR8, known to be used by HIV as coreceptors for infection was not detected by RPA.

Discussion: CXCR4 is a chemokine receptor used as a coreceptor by T cell line-tropic HIV strains which usually emerge later in the course of infection. Its expression has been detected in a broad range of tissues and cell types, including the brain, vascular endothelial cells and some leukocytes but to our knowledge its expression has not been previously reported in the human myocardium. CXCR4 has been clearly associated with CD4-independent HIV-1 and HIV-2 infection. The presence of CXCR4 on myocardium suggests that this chemokine receptor may be involved in HIV infection of the heart. Further studies are underway to elucidate the specific role of this receptor and its ligand in mediating viral entry and their role in HIV related cardiac disease.