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 Hladik, F.
Right arrow Articles by McElrath, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hladik, F.
Right arrow Articles by McElrath, M. J.

 Previous Article  |  Next Article 

Journal of Virology, July 1999, p. 5833-5842, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Dendritic Cell-T-Cell Interactions Support Coreceptor-Independent Human Immunodeficiency Virus Type 1 Transmission in the Human Genital Tract

Florian Hladik,1,2 Gretchen Lentz,3 Robert E. Akridge,2 Greg Peterson,4 Heather Kelley,2 Ami McElroy,1 and M. Juliana McElrath1,2,*

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,1 and Department of Medicine,2 Department of Obstetrics and Gynecology,3 and Department of Laboratory Medicine,4 University of Washington School of Medicine, Seattle, Washington 98145

Received 8 September 1998/Accepted 29 March 1999

Worldwide, human immunodeficiency virus (HIV) is transmitted predominantly by heterosexual contact. Here, we investigate for the first time, by examining mononuclear cells obtained from cervicovaginal tissue, the mechanisms whereby HIV type 1 (HIV-1) directly targets cells from the human genital tract. In contrast to earlier findings in mucosal models such as human skin, we demonstrate that the majority of T cells and macrophages but none or few dendritic cells (DC) express the HIV-1 coreceptor CCR5 in normal human cervicovaginal mucosa, whereas all three cell types express the coreceptor CXCR4. To understand the role of coreceptor expression on infectivity, mucosal mononuclear cells were infected with various HIV-1 isolates, using either CCR5 or CXCR4. Unstimulated T cells become rapidly, albeit nonproductively, infected with R5- and X4-tropic variants. However, DC and T cells form stable conjugates which permit productive infection by viruses of both coreceptor specificities. These results indicate that HIV-1 can exploit T-cell-DC synergism in the human genital tract to overcome potential coreceptor restrictions on DC and postentry blocks of viral replication in unactivated T cells. Thus, mononuclear cells infiltrating the genital mucosa are permissive for transmission of both R5- and X4-tropic HIV-1 variants, and selection of virus variants does not occur by differential expression of HIV-1 coreceptors on genital mononuclear cells.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, Program in Infectious Diseases, 1100 Fairview Ave. North, D3-100, Seattle, WA 98109-1024. Phone: (206) 667-6704. Fax: (206) 667-4411. E-mail: kd{at}u.washington.edu.

Journal of Virology, July 1999, p. 5833-5842, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Doehle, B. P., Hladik, F., McNevin, J. P., McElrath, M. J., Gale, M. Jr. (2009). Human Immunodeficiency Virus Type 1 Mediates Global Disruption of Innate Antiviral Signaling and Immune Defenses within Infected Cells. J. Virol. 83: 10395-10405 [Abstract] [Full Text]  
  • LeBlanc, D. M., Barousse, M. M., Fidel, P. L. Jr. (2006). Role for Dendritic Cells in Immunoregulation during Experimental Vaginal Candidiasis.. Infect. Immun. 74: 3213-3221 [Abstract] [Full Text]  
  • Turville, S. G., Vermeire, K., Balzarini, J., Schols, D. (2005). Sugar-Binding Proteins Potently Inhibit Dendritic Cell Human Immunodeficiency Virus Type 1 (HIV-1) Infection and Dendritic-Cell-Directed HIV-1 Transfer. J. Virol. 79: 13519-13527 [Abstract] [Full Text]  
  • Locher, C. P., Witt, S. A., Kassel, R., Dowell, N. L., Fujimura, S., Levy, J. A. (2005). Differential effects of R5 and X4 human immunodeficiency virus type 1 infection on CD4+ cell proliferation and activation. J. Gen. Virol. 86: 1171-1179 [Abstract] [Full Text]  
  • Dezzutti, C. S., James, V. N., Ramos, A., Sullivan, S. T., Siddig, A., Bush, T. J., Grohskopf, L. A., Paxton, L., Subbarao, S., Hart, C. E. (2004). In Vitro Comparison of Topical Microbicides for Prevention of Human Immunodeficiency Virus Type 1 Transmission. Antimicrob. Agents Chemother. 48: 3834-3844 [Abstract] [Full Text]  
  • Hu, Q., Frank, I., Williams, V., Santos, J. J., Watts, P., Griffin, G. E., Moore, J. P., Pope, M., Shattock, R. J. (2004). Blockade of Attachment and Fusion Receptors Inhibits HIV-1 Infection of Human Cervical Tissue. JEM 199: 1065-1075 [Abstract] [Full Text]  
  • Dang, Q., Chen, J., Unutmaz, D., Coffin, J. M., Pathak, V. K., Powell, D., KewalRamani, V. N., Maldarelli, F., Hu, W.-S. (2004). Nonrandom HIV-1 infection and double infection via direct and cell-mediated pathways. Proc. Natl. Acad. Sci. USA 101: 632-637 [Abstract] [Full Text]  
  • Gummuluru, S., KewalRamani, V. N., Emerman, M. (2002). Dendritic Cell-Mediated Viral Transfer to T Cells Is Required for Human Immunodeficiency Virus Type 1 Persistence in the Face of Rapid Cell Turnover. J. Virol. 76: 10692-10701 [Abstract] [Full Text]  
  • Obert, L. A., Hoover, E. A. (2002). Early Pathogenesis of Transmucosal Feline Immunodeficiency Virus Infection. J. Virol. 76: 6311-6322 [Abstract] [Full Text]  
  • Frank, I., Piatak, M. Jr., Stoessel, H., Romani, N., Bonnyay, D., Lifson, J.D., Pope, M. (2002). Infectious and Whole Inactivated Simian Immunodeficiency Viruses Interact Similarly with Primate Dendritic Cells (DCs): Differential Intracellular Fate of Virions in Mature and Immature DCs. J. Virol. 76: 2936-2951 [Abstract] [Full Text]  
  • Jameson, B., Baribaud, F., Pohlmann, S., Ghavimi, D., Mortari, F., Doms, R. W., Iwasaki, A. (2002). Expression of DC-SIGN by Dendritic Cells of Intestinal and Genital Mucosae in Humans and Rhesus Macaques. J. Virol. 76: 1866-1875 [Abstract] [Full Text]  
  • Turville, S. G., Arthos, J., Mac Donald, K., Lynch, G., Naif, H., Clark, G., Hart, D., Cunningham, A. L. (2001). HIV gp120 receptors on human dendritic cells. Blood 98: 2482-2488 [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]  
  • Cutler, C. W., Jotwani, R., Pulendran, B. (2001). Dendritic Cells: Immune Saviors or Achilles' Heel?. Infect. Immun. 69: 4703-4708 [Full Text]  
  • Schneider-Schaulies, J. (2000). Cellular receptors for viruses: links to tropism and pathogenesis. J. Gen. Virol. 81: 1413-1429 [Full Text]  
  • Hladik, F., Lentz, G., Delpit, E., McElroy, A., McElrath, M. J. (1999). Coexpression of CCR5 and IL-2 in Human Genital But Not Blood T Cells: Implications for the Ontogeny of the CCR5+ Th1 Phenotype. J. Immunol. 163: 2306-2313 [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»