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 (NSI) frequencies, coreceptor usage and gp120 V3 sequences of HIV-1 isolates from Ethiopian AIDS patients.


METHODS
Cross-sectional study on 48 hospitalized AIDS patients (CD4 T cells < 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 were tested by MT-2 assay to determine SI/NSI phenotypes. Lymphocyte subsets were enumerated using Coulter counting and FACScan analysis. Viral load determination used a nucleic acid sequence-based amplification assay (NASBA). Coreceptor usage of HIV-1 biological clones was measured using U87 CD4/chemokine receptor transfectants and phytohemagglutinin-stimulated PBMC of healthy donors with wild-type CCR5 and homozygous mutation CCR5delta32 (a 32 base-pair deletion in CCR5). Reverse transcriptase polymerase chain reaction sequencing was performed on the third variable region (V3) of the HIV-1 gene 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 mean 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 patients were found to be infected with HIV-1 subtype C, based on V3 sequencing. NSI biological clones used CCR5 as coreceptor; SI biological clones used CXCR4 and/or CCR5 and/or CCR3.


CONCLUSIONS
Ethiopian patients with HIV-1 C-subtype AIDS harbour a remarkably low frequency of SI phenotype viruses. Coreceptor usage of these viruses correlates with their biological phenotypes.
Abebe
A
A
Ethiopian-Netherlands AIDS Research Project, Ethiopian Health and Nutrition Research Institute, Addis Ababa. enarp@telecom.net.et
Demissie
D
D
Goudsmit
J
J
Brouwer
M
M
Kuiken
C L
CL
Pollakis
G
G
Schuitemaker
H
H
Fontanet
A L
AL
Rinke de Wit
T F
TF
D000328:Adult; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics; D005002:Ethiopia; D005260:Female; D015726:Giant Cells / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D010446:Peptide Fragments / Q000235:genetics*; D010641:Phenotype; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D015728:Receptors, HIV / Q000378:metabolism*; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D012367:RNA, Viral; D015728:Receptors, HIV