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Journal of Virology, January 2003, p. 1021-1038, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1021-1038.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Comparing the Ex Vivo Fitness of CCR5-Tropic Human Immunodeficiency Virus Type 1 Isolates of Subtypes B and C

Sarah C. Ball,¹ Awet Abraha,¹ Kalonji R. Collins,² Andre J. Marozsan,³ Heather Baird,³ Miguel E. Quiñones-Mateu,⁴ Adam Penn-Nicholson,¹ Michael Murray,¹ Nathalie Richard,¹ Michael Lobritz,¹ Peter A. Zimmerman,⁵ Tatsuyoshi Kawamura,⁶ Andrew Blauvelt,⁶ and Eric J. Arts^1,2,3*

Division of Infectious Diseases, Department of Medicine,¹ Molecular Virology Program,² Department of Pharmacology,³ Division of Geographical Medicine, Department of Medicine, Case Western Reserve University,⁵ Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio,⁴ Dermatology Branch, National Cancer Institute, Bethesda, Maryland⁶

Received 30 July 2002/ Accepted 22 October 2002

Continual human immunodeficiency virus type 1 (HIV-1) evolution and expansion within the human population have led to unequal distribution of HIV-1 group M subtypes. In particular, recent outgrowth of subtype C in southern Africa, India, and China has fueled speculation that subtype C isolates may be more fit in vivo. In this study, nine subtype B and six subtype C HIV-1 isolates were added to peripheral blood mononuclear cell cultures for a complete pairwise competition experiment. All subtype C HIV-1 isolates were less fit than subtype B isolates (P < 0.0001), but intrasubtype variations in HIV-1 fitness were not significant. Increased fitness of subtype B over subtype C was also observed in primary CD4⁺ T cells and macrophages from different human donors but not in skin-derived human Langerhans cells. Detailed analysis of the retroviral life cycle during several B and C virus competitions indicated that the efficiency of host cell entry may have a significant impact on relative fitness. Furthermore, phyletic analyses of fitness differences suggested that, for a recombined subtype B/C HIV-1 isolate, higher fitness mapped to the subtype B env gene rather than the subtype C gag and pol genes. These results suggest that subtype B and C HIV-1 may be transmitted with equal efficiency (Langerhans cell data) but that subtype C isolates may be less fit following initial infection (T-cell and macrophage data) and may lead to slower disease progression.

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* Corresponding author. Mailing address: Division of Infectious Diseases, BRB 1029, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106. Phone: (216) 368-8904. Fax (216)-368 2034. E-mail: eja3{at}po.cwru.edu.

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Journal of Virology, January 2003, p. 1021-1038, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1021-1038.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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