High frequency of syncytium-inducing and CXCR4-tropic viruses among human immunodeficiency virus type 1 subtype C-infected patients receiving antiretroviral treatment.
Human immunodeficiency virus type 1 (HIV-1) subtype C viruses have been found to almost exclusively use the chemokine receptor CCR5 as a coreceptor for entry, even in patients with advanced AIDS. We have characterized subtype C virus isolates from 28 patients from Harare, Zimbabwe, 20 of whom were receiving antiretroviral treatment. Virus from 10 of the treated patients induced syncytium formation (SI virus) when cultured with MT2 cells. Only non-syncytium-inducing (NSI) virus was cultured from the peripheral blood mononuclear cells of the eight patients who had not received treatment. The majority of these subtype C SI viruses were capable of using both CCR5 and CXCR4 as coreceptors for viral entry, and the consensus V3 loop sequences from the SI viruses displayed a high net charge compared to those of NSI viruses. While those on treatment had reverse transcriptase (RT) and protease mutations, there was no clear association between RT and protease drug resistance mutations and coreceptor tropism. These results suggest that CXCR4-tropic viruses are present within the quasispecies of patients infected with subtype C virus and that antiretroviral treatment may create an environment for the emergence of CXCR4 tropism.
Johnston
Elizabeth R
ER
Division of Infectious Diseases and AIDS Research, Stanford University, Stanford, California 94035, USA. betsyj@stanford.edu
Zijenah
Lynn S
LS
Mutetwa
Solomon
S
Kantor
Rami
R
Kittinunvorakoon
Chonticha
C
Katzenstein
David A
DA
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D015726:Giant Cells; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry; D010802:Phylogeny; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D019562:Viral Load
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019718:Receptors, CXCR4