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Journal of Virology, June 2009, p. 5592-5605, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02051-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

CCR5- and CXCR4-Tropic Subtype C Human Immunodeficiency Virus Type 1 Isolates Have a Lower Level of Pathogenic Fitness than Other Dominant Group M Subtypes: Implications for the Epidemic{triangledown} ,{ddagger}

Awet Abraha,1,{dagger} Immaculate L. Nankya,2,{dagger} Richard Gibson,1 Korey Demers,1 Denis M. Tebit,1 Elizabeth Johnston,3 David Katzenstein,3 Asna Siddiqui,4 Carolina Herrera,4 Lucia Fischetti,4 Robin J. Shattock,4 and Eric J. Arts1,2*

Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio,1 Virology Program, Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio,2 Infectious Diseases and Geographical Medicine, Department of Medicine, Stanford University, Stanford, California,3 Center for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom4

Received 29 September 2008/ Accepted 11 March 2009

Human immunodeficiency virus type 1 (HIV-1) subtype C is the dominant subtype globally, due largely to the incidence of subtype C infections in sub-Saharan Africa and east Asia. We compared the relative replicative fitness (ex vivo) of the major (M) group of HIV-1 subtypes A, B, C, D, and CRF01_AE and group O isolates. To estimate pathogenic fitness, pairwise competitions were performed between CCR5-tropic (R5) or CXCR4-tropic (X4) virus isolates in peripheral blood mononuclear cells (PBMC). A general fitness order was observed among 33 HIV-1 isolates; subtype B and D HIV-1 isolates were slightly more fit than the subtype A and dramatically more fit than the 12 subtype C isolates. All group M isolates were more fit (ex vivo) than the group O isolates. To estimate ex vivo transmission fitness, a subset of primary HIV-1 isolates were examined in primary human explants from penile, cervical, and rectal tissues. Only R5 isolates and no X4 HIV-1 isolates could replicate in these tissues, whereas the spread to PM1 cells was dependent on active replication and passive virus transfer. In tissue competition experiments, subtype C isolates could compete with and, in some cases, even win over subtype A and D isolates. However, when the migratory cells from infected tissues were mixed with a susceptible cell line, the subtype C isolates were outcompeted by other subtypes, as observed in experiments with PBMC. These findings suggest that subtype C HIV-1 isolates might have equal transmission fitness but reduced pathogenic fitness relative to other group M HIV-1 isolates.

* Corresponding author. Mailing address: Division of Infectious Diseases, BRB 1034, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106. Phone: (216) 368-8904. Fax: (216) 368-2034. E-mail: eja3{at}case.edu

{triangledown} Published ahead of print on 18 March 2009.

{ddagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{dagger} A.A. and I.L.N. contributed equally to this study.

Journal of Virology, June 2009, p. 5592-5605, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02051-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Geuenich, S., Kaderali, L., Allespach, I., Sertel, S., Keppler, O. T. (2009). Biological Signature Characteristics of Primary Isolates from Human Immunodeficiency Virus Type 1 Group O in Ex Vivo Human Tonsil Histocultures. J. Virol. 83: 10494-10503 [Abstract] [Full Text]  


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