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Journal of Virology, December 2006, p. 11776-11790, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01730-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Ming Li,1 Jesus F. Salazar-Gonzalez,2 Cynthia A. Derdeyn,3 Lynn Morris,4 Carolyn Williamson,5 James E. Robinson,6 Julie M. Decker,2 Yingying Li,2 Maria G. Salazar,2 Victoria R. Polonis,7 Koleka Mlisana,8 Salim Abdool Karim,8 Kunxue Hong,9 Kelli M. Greene,1 Miroslawa Bilska,1 Jintao Zhou,1 Susan Allen,10 Elwyn Chomba,11 Joseph Mulenga,12 Cheswa Vwalika,13 Feng Gao,14 Ming Zhang,15 Bette T. M. Korber,15 Eric Hunter,3 Beatrice H. Hahn,2 and David C. Montefiori1*

Departments of Surgery,1 Medicine, Duke University Medical Center, Durham, North Carolina 27710,14 Department of Medicine, University of Alabama, Birmingham, Alabama 35294,2 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30329,3 National Institute for Communicable Diseases, Johannesburg, South Africa,4 Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa,5 Department of Pediatrics, Tulane University Medical Center, New Orleans, Louisiana 70112,6 Walter Reed Army Institute of Research, Rockville, Maryland 20850,7 CAPRISA, University of KwaZulu-Natal, Durban, South Africa,8 Division of Virology and Immunology, National Center for AIDS, Beijing, China,9 Department of Global Health, Emory University, Atlanta, Georgia,10 University Teaching Hospital,11 Zambia National Blood Transfusion Service,12 Zambia-Emory HIV Research Program, Lusaka, Zambia,13 Los Alamos National Laboratory, Los Alamos, New Mexico 87545,15

Received 10 August 2006/ Accepted 5 September 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.

* Corresponding author. Mailing address: Department of Surgery, Laboratory for AIDS Vaccine Research and Development, P.O. Box 2926, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-5278. Fax: (919) 684-4288. E-mail: monte{at}acpub.duke.edu.

{triangledown} Published ahead of print on 13 September 2006.

Journal of Virology, December 2006, p. 11776-11790, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01730-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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