Cell membrane proteins and quasispecies compartmentalization of CSF and plasma HIV-1 from aids patients with neurological disorders

Abstract

Cell membrane protein (CMP) profile of HIV-1 from cerebrospinal fluid (CSF) and plasma of five AIDS patients with neurologic disorders was analyzed and compared with viral quasispecies composition in these body compartments. To this aim, paired CSF and plasma samples from AIDS subjects with HIV-related neurological diseases (three HIV-1 encephalopaty (HIVE) and two primary CNS lymphoma (PCNSL)) underwent immobilized antibody capture (IAC) assay to determine the profile of CMP acquired by HIV-1. The considered CMPs were CD45RO, CD26, CD36, glut-R, N-CAM, VCAM-1, ELAM-1, CD44 and CD58, representing lymphomonocyte, neuronal and adhesion molecules. Cloning and sequencing of env and gag regions was performed to predict coreceptor usage and to analyze quasispecies compartmentalization. The results indicated that CD44 and CD58 were the most represented molecules on HIV-1 from CSF, whereas CD36 was the most abundant molecule on plasma HIV-1. V3 env aminoacidic sequences and net charge were consistent with M-R5 phenotype in all CSF and in most plasma clones. The degree of genetic heterogeneity (both complexity and diversity) in p17 gag was significantly lower in CSF-HIV than that in plasma-HIV for three patients, higher for one patient, and not significantly different for one patient, suggesting compartmentalization for all but the latter patient. When considering the pattern of CMP, the most abundant CMP observed in HIV from plasma and CSF was different in patients showing compartmentalization, while was the same in the patient without significant differences in CSF and plasma quasispecies. In conclusion, the present data on CMP pattern, V3 loop aminoacidic signature and genetic heterogeneity of HIV-1 quasispecies from CSF and plasma of HIVE patients, are consistent with a compartmentalized virus replication, at least in some patients, and with a possible different source of HIV in the two body sites, even though in a context of a largely prevalent M-R5 phenotype.