title: Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in Southern Africa.
abstract: A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Zambia. In general, the gp120 region of these clones was shorter (most evident in V1 and V4) and less glycosylated compared to newly transmitted subtype B viruses, and it was underglycosylated but no different in length compared to chronic subtype C viruses. The gp120s also exhibited low amino acid sequence variability (12%) in V3 and high variability (39%) immediately downstream of V3, a feature shared with newly transmitted subtype B viruses and chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a luciferase reporter gene assay, all clones possessed an R5 phenotype and resembled primary isolates in their sensitivity to neutralization by HIV-1-positive plasmas. Results obtained with a multisubtype plasma panel suggested partial subtype preference in the neutralizing antibody response to infection. The clones were typical of subtype C in that all were resistant to 2G12 (associated with loss of N-glycosylation at position 295) and most were resistant to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor binding domain of gp120 were poorly accessible and were difficult to induce and stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines. A subset of these gp160 clones are suitable for use as reference reagents to facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.
authors.affiliation: Department of Surgery, Laboratory for AIDS Vaccine Research and Development, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Derdeyn
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
authors.forename: Julie M
authors.initials: JM
authors.lastname: Decker
authors.forename: Yingying
authors.initials: Y
authors.lastname: Li
authors.forename: Maria G
authors.initials: MG
authors.lastname: Salazar
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.forename: Salim Abdool
authors.initials: SA
authors.lastname: Karim
authors.forename: Kunxue
authors.initials: K
authors.lastname: Hong
authors.forename: Kelli M
authors.initials: KM
authors.lastname: Greene
authors.forename: Miroslawa
authors.initials: M
authors.lastname: Bilska
authors.forename: Jintao
authors.initials: J
authors.lastname: Zhou
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: Elwyn
authors.initials: E
authors.lastname: Chomba
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: Cheswa
authors.initials: C
authors.lastname: Vwalika
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Bette T M
authors.initials: BT
authors.lastname: Korber
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
mesh_terms: D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D020010:Heterosexuality; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013019:South Africa
chemical_list: D015686:Gene Products, env; D015483:HIV Antibodies