This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Reeves, J. D.
Right arrow Articles by Clapham, P. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Reeves, J. D.
Right arrow Articles by Clapham, P. R.

 Previous Article  |  Next Article 

Journal of Virology, September 1999, p. 7795-7804, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Primary Human Immunodeficiency Virus Type 2 (HIV-2) Isolates Infect CD4-Negative Cells via CCR5 and CXCR4: Comparison with HIV-1 and Simian Immunodeficiency Virus and Relevance to Cell Tropism In Vivo

Jacqueline D. Reeves,1,* Sam Hibbitts,1 Graham Simmons,1 Áine McKnight,1 José M. Azevedo-Pereira,2 José Moniz-Pereira,2 and Paul R. Clapham1,*

The Wohl Virion Centre, Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, London, United Kingdom,1 and Faculdade de Farmacia, Universidade de Lisboa, Lisbon, Portugal2

Received 1 April 1999/Accepted 7 June 1999

Cell surface receptors exploited by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) for infection are major determinants of tropism. HIV-1 usually requires two receptors to infect cells. Gp120 on HIV-1 virions binds CD4 on the cell surface, triggering conformational rearrangements that create or expose a binding site for a seven-transmembrane (7TM) coreceptor. Although HIV-2 and SIV strains also use CD4, several laboratory-adapted HIV-2 strains infect cells without CD4, via an interaction with the coreceptor CXCR4. Moreover, the envelope glycoproteins of SIV of macaques (SIVMAC) can bind to and initiate infection of CD4- cells via CCR5. Here, we show that most primary HIV-2 isolates can infect either CCR5+ or CXCR4+ cells without CD4. The efficiency of CD4-independent infection by HIV-2 was comparable to that of SIV, but markedly higher than that of HIV-1. CD4-independent HIV-2 strains that could use both CCR5 and CXCR4 to infect CD4+ cells were only able to use one of these receptors in the absence of CD4. Our observations therefore indicate (i) that HIV-2 and SIV envelope glycoproteins form a distinct conformation that enables contact with a 7TM receptor without CD4, and (ii) the use of CD4 enables a wider range of 7TM receptors to be exploited for infection and may assist adaptation or switching to new coreceptors in vivo. Primary CD4- fetal astrocyte cultures expressed CXCR4 and supported replication by the T-cell-line-adapted ROD/B strain. Productive infection by primary X4 strains was only triggered upon treatment of virus with soluble CD4. Thus, many primary HIV-2 strains infect CCR5+ or CXCR4+ cell lines without CD4 in vitro. CD4- cells that express these coreceptors in vivo, however, may still resist HIV-2 entry due to insufficient coreceptor concentration on the cell surface to trigger fusion or their expression in a conformation nonfunctional as a coreceptor. Our study, however, emphasizes that primary HIV-2 strains carry the potential to infect CD4- cells expressing CCR5 or CXCR4 in vivo.

* Corresponding author. Mailing address: The Wohl Virion Centre, Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland St., London W1P 6DB, United Kingdom. Phone: 44 171-504 9562 or 44 171-504 9558. Fax: 44 171-504 9555. E-mail: j.reeves{at}ucl.ac.uk or p.clapham{at}ucl.ac.uk.

Journal of Virology, September 1999, p. 7795-7804, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Mukherjee, S., Lee, H.-L. R., Ron, Y., Dougherty, J. P. (2006). Proviral Progeny of Heterodimeric Virions Reveal a High Crossover Rate for Human Immunodeficiency Virus Type 2. J. Virol. 80: 12402-12407 [Abstract] [Full Text]  
  • Jones, K. S., Fugo, K., Petrow-Sadowski, C., Huang, Y., Bertolette, D. C., Lisinski, I., Cushman, S. W., Jacobson, S., Ruscetti, F. W. (2006). Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Use Different Receptor Complexes To Enter T Cells.. J. Virol. 80: 8291-8302 [Abstract] [Full Text]  
  • Marchant, D., Neil, S. J. D., McKnight, A. (2006). Human immunodeficiency virus types 1 and 2 have different replication kinetics in human primary macrophage culture. J. Gen. Virol. 87: 411-418 [Abstract] [Full Text]  
  • Shi, Y., Brandin, E., Vincic, E., Jansson, M., Blaxhult, A., Gyllensten, K., Moberg, L., Brostrom, C., Fenyo, E. M., Albert, J. (2005). Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation. J. Gen. Virol. 86: 3385-3396 [Abstract] [Full Text]  
  • Wyss, S., Dimitrov, A. S., Baribaud, F., Edwards, T. G., Blumenthal, R., Hoxie, J. A. (2005). Regulation of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Fusion by a Membrane-Interactive Domain in the gp41 Cytoplasmic Tail. J. Virol. 79: 12231-12241 [Abstract] [Full Text]  
  • Neil, S. J. D., Aasa-Chapman, M. M. I., Clapham, P. R., Nibbs, R. J., McKnight, A., Weiss, R. A. (2005). The Promiscuous CC Chemokine Receptor D6 Is a Functional Coreceptor for Primary Isolates of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 on Astrocytes. J. Virol. 79: 9618-9624 [Abstract] [Full Text]  
  • Zerhouni, B., Nelson, J. A. E., Saha, K. (2004). CXCR4-Dependent Infection of CD8+, but Not CD4+, Lymphocytes by a Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol. 78: 12288-12296 [Abstract] [Full Text]  
  • Peters, P. J., Bhattacharya, J., Hibbitts, S., Dittmar, M. T., Simmons, G., Bell, J., Simmonds, P., Clapham, P. R. (2004). Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages. J. Virol. 78: 6915-6926 [Abstract] [Full Text]  
  • Pohlmann, S., Davis, C., Meister, S., Leslie, G. J., Otto, C., Reeves, J. D., Puffer, B. A., Papkalla, A., Krumbiegel, M., Marzi, A., Lorenz, S., Munch, J., Doms, R. W., Kirchhoff, F. (2004). Amino Acid 324 in the Simian Immunodeficiency Virus SIVmac V3 Loop Can Confer CD4 Independence and Modulate the Interaction with CCR5 and Alternative Coreceptors. J. Virol. 78: 3223-3232 [Abstract] [Full Text]  
  • Zerhouni, B., Nelson, J. A. E., Saha, K. (2004). Isolation of CD4-Independent Primary Human Immunodeficiency Virus Type 1 Isolates That Are Syncytium Inducing and Acutely Cytopathic for CD8+ Lymphocytes. J. Virol. 78: 1243-1255 [Abstract] [Full Text]  
  • Willey, S. J., Reeves, J. D., Hudson, R., Miyake, K., Dejucq, N., Schols, D., Clercq, E. D., Bell, J., McKnight, A., Clapham, P. R. (2003). Identification of a Subset of Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus Strains Able To Exploit an Alternative Coreceptor on Untransformed Human Brain and Lymphoid Cells. J. Virol. 77: 6138-6152 [Abstract] [Full Text]  
  • Lin, G., Baribaud, F., Romano, J., Doms, R. W., Hoxie, J. A. (2002). Identification of gp120 Binding Sites on CXCR4 by Using CD4-Independent Human Immunodeficiency Virus Type 2 Env Proteins. J. Virol. 77: 931-942 [Abstract] [Full Text]  
  • Clapham, P. R., McKnight, A. (2002). Cell surface receptors, virus entry and tropism of primate lentiviruses. J. Gen. Virol. 83: 1809-1829 [Abstract] [Full Text]  
  • Ryzhova, E., Whitbeck, J. C., Canziani, G., Westmoreland, S. V., Cohen, G. H., Eisenberg, R. J., Lackner, A., Gonzalez-Scarano, F. (2002). Rapid Progression to Simian AIDS Can Be Accompanied by Selection of CD4-Independent gp120 Variants with Impaired Ability To Bind CD4. J. Virol. 76: 7903-7909 [Abstract] [Full Text]  
  • Reeves, J. D., Doms, R. W. (2002). Human immunodeficiency virus type 2. J. Gen. Virol. 83: 1253-1265 [Full Text]  
  • Habasque, C., Aubry, F., Jegou, B., Samson, M. (2002). Study of the HIV-1 receptors CD4, CXCR4, CCR5 and CCR3 in the human and rat testis. Mol Hum Reprod 8: 419-425 [Abstract] [Full Text]  
  • Lin, G., Lee, B., Haggarty, B. S., Doms, R. W., Hoxie, J. A. (2001). CD4-Independent Use of Rhesus CCR5 by Human Immunodeficiency Virus Type 2 Implicates an Electrostatic Interaction between the CCR5 N Terminus and the gp120 C4 Domain. J. Virol. 75: 10766-10778 [Abstract] [Full Text]  
  • Overbaugh, J., Miller, A. D., Eiden, M. V. (2001). Receptors and Entry Cofactors for Retroviruses Include Single and Multiple Transmembrane-Spanning Proteins as well as Newly Described Glycophosphatidylinositol-Anchored and Secreted Proteins. Microbiol. Mol. Biol. Rev. 65: 371-389 [Abstract] [Full Text]  
  • Edwards, T. G., Hoffman, T. L., Baribaud, F., Wyss, S., LaBranche, C. C., Romano, J., Adkinson, J., Sharron, M., Hoxie, J. A., Doms, R. W. (2001). Relationships between CD4 Independence, Neutralization Sensitivity, and Exposure of a CD4-Induced Epitope in a Human Immunodeficiency Virus Type 1 Envelope Protein. J. Virol. 75: 5230-5239 [Abstract] [Full Text]  
  • Dumonceaux, J., Goujon, C., Joliot, V., Briand, P., Hazan, U. (2001). Determination of Essential Amino Acids Involved in the CD4-Independent Tropism of the X4 Human Immunodeficiency Virus Type 1 m7NDK Isolate: Role of Potential N Glycosylations in the C2 and V3 Regions of gp120. J. Virol. 75: 5425-5428 [Abstract] [Full Text]  
  • Mori, K., Rosenzweig, M., Desrosiers, R. C. (2000). Mechanisms for Adaptation of Simian Immunodeficiency Virus to Replication in Alveolar Macrophages. J. Virol. 74: 10852-10859 [Abstract] [Full Text]  
  • Doms, R. W., Trono, D. (2000). The plasma membrane as a combat zone in the HIV battlefield. Genes Dev. 14: 2677-2688 [Full Text]  
  • MOORE, J. P., DOMS, R. W. (2000). HIV: Much at Stake with Kidneys?. J. Am. Soc. Nephrol. 11: 2138-2140 [Full Text]  
  • Borsetti, A., Parolin, C., Ridolfi, B., Sernicola, L., Geraci, A., Ensoli, B., Titti, F. (2000). CD4-Independent Infection of Two CD4-/CCR5-/CXCR4+ Pre-T-Cell Lines by Human and Simian Immunodeficiency Viruses. J. Virol. 74: 6689-6694 [Abstract] [Full Text]  
  • Owen, S. M., Masciotra, S., Novembre, F., Yee, J., Switzer, W. M., Ostyula, M., Lal, R. B. (2000). Simian Immunodeficiency Viruses of Diverse Origin Can Use CXCR4 as a Coreceptor for Entry into Human Cells. J. Virol. 74: 5702-5708 [Abstract] [Full Text]  
  • Chabot, D. J., Chen, H., Dimitrov, D. S., Broder, C. C. (2000). N-Linked Glycosylation of CXCR4 Masks Coreceptor Function for CCR5-Dependent Human Immunodeficiency Virus Type 1 Isolates. J. Virol. 74: 4404-4413 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»