Genotypic characterization and comparison of full-length envelope glycoproteins from South African HIV type 1 subtype C primary isolates that utilize CCR5 and/or CXCR4.
CCR5 has preferentially been used by all circulating HIV-1 subtype C viruses for cell entry. Recently, we reported the highest proportion of CXCR4-utilizing primary isolates among a cohort of 20 South African AIDS patients. This study describes and compares the Env genotypic characteristics from these 20 HIV-1 subtype C (and unique CD recombinant) primary isolates. Fourteen primary isolates utilized CCR5, four (including the CD recombinant) used CXCR4, and two were dual tropic. Extensive analysis and comparison of important structural motifs such as the N-linked glycosylation sites, signal sequences, CD4-binding sites, variable loops, cleavage sites, known neutralizing antibody and small molecule inhibitor binding sites confirmed that other than the expected differences in the V3 loop, no sequence motifs distinguished between R5 and X4 tropism. Further correlation of the env genotype to functionally relevant motifs is necessary to elucidate the relationship between biologically and immunologically relevant sites and aid vaccine and novel drug design.
HIV Pathogenesis Research Laboratory, Department of Molecular Medicine and Haematology, University of the Witwatersrand Medical School, Parktown, Johannesburg, 2193, South Africa.
Katherine
K
Michler
Bridgette J
BJ
Connell
Willem D F
WD
Venter
Wendy S
WS
Stevens
Alexio
A
Capovilla
Maria A
MA
Papathanasopoulos
D000595:Amino Acid Sequence; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D016415:Sequence Alignment; D013019:South Africa; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D054299:env Gene Products, Human Immunodeficiency Virus