The CCR5 and CXCR4 coreceptors are both used by human immunodeficiency virus type 1 primary isolates from subtype C.
Human immunodeficiency virus type 1 (HIV-1) subtype C viruses with different coreceptor usage profiles were isolated from 29 South African patients with advanced AIDS. All 24 R5 isolates were inhibited by the CCR5-specific agents, PRO 140 and RANTES, while the two X4 viruses and the three R5X4 viruses were sensitive to the CXCR4-specific inhibitor, AMD3100. The five X4 or R5X4 viruses were all able to replicate in peripheral blood mononuclear cells that did not express CCR5. When tested using coreceptor-transfected cell lines, one R5 virus was also able to use CXCR6, and another R5X4 virus could use CCR3, BOB/GPR15, and CXCR6. The R5X4 and X4 viruses contained more-diverse V3 loop sequences, with a higher overall positive charge, than the R5 viruses. Hence, some HIV-1 subtype C viruses are able to use CCR5, CXCR4, or both CXCR4 and CCR5 for entry, and they are sensitive to specific inhibitors of entry via these coreceptors. These observations are relevant to understanding the rapid spread of HIV-1 subtype C in the developing world and to the design of intervention and treatment strategies.
Cilliers
Tonie
T
AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa.
Nhlapo
Jabulani
J
Coetzer
Mia
M
Orlovic
Dragana
D
Ketas
Thomas
T
Olson
William C
WC
Moore
John P
JP
Trkola
Alexandra
A
Morris
Lynn
L
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology; D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001596:Benzylamines; D065100:CCR5 Receptor Antagonists; D002460:Cell Line; D018946:Chemokine CCL5 / Q000494:pharmacology; D000080027:Cyclams; D005260:Female; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015728:Receptors, HIV / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013019:South Africa; D014162:Transfection; D014779:Virus Replication
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001596:Benzylamines; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5; D000080027:Cyclams; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D006571:Heterocyclic Compounds; D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV; C088327:plerixafor; C420063:leronlimab