HIV-1 subtype C syncytium- and non-syncytium-inducing phenotypes and coreceptor usage among Ethiopian patients with AIDS

Objective: To assess syncytium-inducing (SI) and non-syncytium-inducing (NS I) frequencies, coreceptor usage and gp120 V3 sequences of HIV-1 isolates f rom Ethiopian AIDS patients. Patients: Cross-sectional study on 48 hospitalized AIDS patients (CD4 T cel ls < 200 x 10(6) cell/l) with stage III or IV of the WHO staging system for HIV-1 infection and disease. Methods: Peripheral blood mononuclear cells (PBMC) from all 48 patients wer e tested by MT-2 assay to determine SI/NSI phenotypes. Lymphocyte subsets w ere enumerated using Coulter counting and FACScan analysis. Viral load dete rmination used a nucleic acid sequence-based amplification assay (NASBA). C oreceptor usage of HIV-1 biological clones was measured using U87 CD4/chemo kine receptor transfectants and phytohemaggrutinin-stimulated PBMC of healt hy donors with wildtype CCR5 and homozygous mutation CCR5 Delta 32 (a 32 ba se-pair deletion in CCR5). Reverse transcriptase polymerase chain reaction sequencing was performed on the third variable region (V3) of the HIV-1 gen e gp120. Sequence alignments were done manually; phylogenetic analyses used PHYLIP software packages. Results: SI viruses were detected for 3/48 (6%) AIDS patients only. Lower m ean absolute CD4 counts were determined in patients with SI virus compared with NSI (P = 0.04), but no differences in viral load were observed. All pa tients were found to be infected with HIV-1 subtype C, based on V3 sequenci ng. NSI biological clones used CCR5 as coreceptor; SI biological clones use d CXCR4 and/or CCR5 and/or CCR3. Conclusions: Ethiopian patients with HIV-1 C-subtype AIDS harbour a remarka bly low frequency of SI phenotype viruses. Coreceptor usage of these viruse s correlates with their biological phenotypes. (C) 1999 Lippincott Williams & Wilkins.