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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.

Publication ,  Journal Article
Li, M; Salazar-Gonzalez, JF; Derdeyn, CA; Morris, L; Williamson, C; Robinson, JE; Decker, JM; Li, Y; Salazar, MG; Polonis, VR; Mlisana, K ...
Published in: J Virol
December 2006

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.

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

December 2006

Volume

80

Issue

23

Start / End Page

11776 / 11790

Location

United States

Related Subject Headings

  • Virology
  • South Africa
  • Sequence Analysis, DNA
  • Phylogeny
  • Neutralization Tests
  • Molecular Sequence Data
  • Humans
  • Heterosexuality
  • HIV-1
  • HIV Infections
 

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MLA
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Li, M., Salazar-Gonzalez, J. F., Derdeyn, C. A., Morris, L., Williamson, C., Robinson, J. E., … Montefiori, D. C. (2006). 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. J Virol, 80(23), 11776–11790. https://doi.org/10.1128/JVI.01730-06
Li, Ming, Jesus F. Salazar-Gonzalez, Cynthia A. Derdeyn, Lynn Morris, Carolyn Williamson, James E. Robinson, Julie M. Decker, et al. “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.J Virol 80, no. 23 (December 2006): 11776–90. https://doi.org/10.1128/JVI.01730-06.
Li M, Salazar-Gonzalez JF, Derdeyn CA, Morris L, Williamson C, Robinson JE, Decker JM, Li Y, Salazar MG, Polonis VR, Mlisana K, Karim SA, Hong K, Greene KM, Bilska M, Zhou J, Allen S, Chomba E, Mulenga J, Vwalika C, Gao F, Zhang M, Korber BTM, Hunter E, Hahn BH, Montefiori DC. 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. J Virol. 2006 Dec;80(23):11776–11790.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

December 2006

Volume

80

Issue

23

Start / End Page

11776 / 11790

Location

United States

Related Subject Headings

  • Virology
  • South Africa
  • Sequence Analysis, DNA
  • Phylogeny
  • Neutralization Tests
  • Molecular Sequence Data
  • Humans
  • Heterosexuality
  • HIV-1
  • HIV Infections