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 Hu, Q.-x.
Right arrow Articles by Greenberg, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hu, Q.-x.
Right arrow Articles by Greenberg, M. L.

 Previous Article  |  Next Article 

Journal of Virology, December 2000, p. 11858-11872, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Evolution of the Human Immunodeficiency Virus Type 1 Envelope during Infection Reveals Molecular Corollaries of Specificity for Coreceptor Utilization and AIDS Pathogenesis

Qin-xue Hu,1,dagger Ashley Perkins Barry,2,Dagger Zi-xuan Wang,1 Shanon M. Connolly,2 Stephen C. Peiper,1 and Michael L. Greenberg2,*

Henry Vogt Cancer Research Institute, University of Louisville, Louisville, Kentucky,1 and Department of Surgery, Duke University Medical Center, Durham, North Carolina2

Received 10 December 1999/Accepted 15 September 2000

The evolution of human immunodeficiency virus type 1 infection is associated with a shift in the target cell population, driven by variability in coreceptor utilization resulting from diversity in env. To elucidate the potential consequences of these changes for Env-mediated fusion over the course of AIDS, we examined the biological properties of serial viral isolates and determined coreceptor utilization by the products of env cloned from two individuals, followed from the detection of seroconversion throughout the course of their infection. One had a typical course, and the other had an accelerated progression. Early isolates were non-syncytium inducing, and the corresponding Env exclusively utilized CCR5, whereas Env from late phases of infection showed restricted utilization of CXCR4 in both patients. Env from subject SC24, who had a standard progression, demonstrated multitropism, manifested by utilization of CCR3, CXCR4, and CCR5 in the intervening period. In contrast, Env from patient SC51, who experienced early conversion to the syncytium-inducing phenotype, developed dualtropic coreceptor utilization of CCR5 and CXCR4. Genetic analysis of env from each isolate revealed that those with an X4 phenotype formed a distinct subcluster within each subject. Analysis of chimeras constructed from R5 and multispecific env from patient SC24 demonstrated that while the V3 domain played a dominant role in determining coreceptor utilization, sequences in the V4-V5 region also contributed to the latter phenotype. Immunoprecipitation experiments confirmed that the hybrid Env proteins were expressed at similar levels. These experiments demonstrate that progression from the R5 to X4 phenotype may occur through a multi- or dual-tropic intermediate and that multiple domains contribute to this process.

* Corresponding author. Mailing address: Center For AIDS Research, Box 2926, Rm. 113 SORF Bldg., Department of Surgery, Duke University Medical Center, Durham, NC 27710. Phone: (919) 681-5598. Fax: (919) 684-4288. E-mail: green030{at}mc.duke.edu.

dagger Present address: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, People's Republic of China.

Dagger Present address: Yerkes Regional Primate Center, Emory University, Atlanta, GA 30329.

Journal of Virology, December 2000, p. 11858-11872, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Hanna, Z., Priceputu, E., Chrobak, P., Hu, C., Dugas, V., Goupil, M., Marquis, M., de Repentigny, L., Jolicoeur, P. (2009). Selective Expression of Human Immunodeficiency Virus Nef in Specific Immune Cell Populations of Transgenic Mice Is Associated with Distinct AIDS-Like Phenotypes. J. Virol. 83: 9743-9758 [Abstract] [Full Text]  
  • Coetzer, M., Nedellec, R., Salkowitz, J., McLaughlin, S., Liu, Y., Heath, L., Mullins, J. I., Mosier, D. E. (2008). Evolution of CCR5 Use before and during Coreceptor Switching. J. Virol. 82: 11758-11766 [Abstract] [Full Text]  
  • Veazey, R. S., Ketas, T. A., Klasse, P. J., Davison, D. K., Singletary, M., Green, L. C., Greenberg, M. L., Moore, J. P. (2008). Tropism-independent protection of macaques against vaginal transmission of three SHIVs by the HIV-1 fusion inhibitor T-1249. Proc. Natl. Acad. Sci. USA 105: 10531-10536 [Abstract] [Full Text]  
  • Dwyer, J. J., Wilson, K. L., Davison, D. K., Freel, S. A., Seedorff, J. E., Wring, S. A., Tvermoes, N. A., Matthews, T. J., Greenberg, M. L., Delmedico, M. K. (2007). Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus. Proc. Natl. Acad. Sci. USA 104: 12772-12777 [Abstract] [Full Text]  
  • Ghaffari, G., Tuttle, D. L., Briggs, D., Burkhardt, B. R., Bhatt, D., Andiman, W. A., Sleasman, J. W., Goodenow, M. M. (2005). Complex Determinants in Human Immunodeficiency Virus Type 1 Envelope gp120 Mediate CXCR4-Dependent Infection of Macrophages. J. Virol. 79: 13250-13261 [Abstract] [Full Text]  
  • Mink, M., Mosier, S. M., Janumpalli, S., Davison, D., Jin, L., Melby, T., Sista, P., Erickson, J., Lambert, D., Stanfield-Oakley, S. A., Salgo, M., Cammack, N., Matthews, T., Greenberg, M. L. (2005). Impact of Human Immunodeficiency Virus Type 1 gp41 Amino Acid Substitutions Selected during Enfuvirtide Treatment on gp41 Binding and Antiviral Potency of Enfuvirtide In Vitro. J. Virol. 79: 12447-12454 [Abstract] [Full Text]  
  • Ren, X., Sodroski, J., Yang, X. (2005). An Unrelated Monoclonal Antibody Neutralizes Human Immunodeficiency Virus Type 1 by Binding to an Artificial Epitope Engineered in a Functionally Neutral Region of the Viral Envelope Glycoproteins. J. Virol. 79: 5616-5624 [Abstract] [Full Text]  
  • Xu, L., Pozniak, A., Wildfire, A., Stanfield-Oakley, S. A., Mosier, S. M., Ratcliffe, D., Workman, J., Joall, A., Myers, R., Smit, E., Cane, P. A., Greenberg, M. L., Pillay, D. (2005). Emergence and Evolution of Enfuvirtide Resistance following Long-Term Therapy Involves Heptad Repeat 2 Mutations within gp41. Antimicrob. Agents Chemother. 49: 1113-1119 [Abstract] [Full Text]  
  • Zhang, M., Gaschen, B., Blay, W., Foley, B., Haigwood, N., Kuiken, C., Korber, B. (2004). Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14: 1229-1246 [Abstract] [Full Text]  
  • Karlsson, I., Antonsson, L., Shi, Y., Oberg, M., Karlsson, A., Albert, J., Olde, B., Owman, C., Jansson, M., Fenyo, E. M. (2004). Coevolution of RANTES Sensitivity and Mode of CCR5 Receptor Use by Human Immunodeficiency Virus Type 1 of the R5 Phenotype. J. Virol. 78: 11807-11815 [Abstract] [Full Text]  
  • Ohagen, A., Devitt, A., Kunstman, K. J., Gorry, P. R., Rose, P. P., Korber, B., Taylor, J., Levy, R., Murphy, R. L., Wolinsky, S. M., Gabuzda, D. (2003). Genetic and Functional Analysis of Full-Length Human Immunodeficiency Virus Type 1 env Genes Derived from Brain and Blood of Patients with AIDS. J. Virol. 77: 12336-12345 [Abstract] [Full Text]  
  • Poumbourios, P., Maerz, A. L., Drummer, H. E. (2003). Functional Evolution of the HIV-1 Envelope Glycoprotein 120 Association Site of Glycoprotein 41. J. Biol. Chem. 278: 42149-42160 [Abstract] [Full Text]  
  • Painter, S. L., Biek, R., Holley, D. C., Poss, M. (2003). Envelope Variants from Women Recently Infected with Clade A Human Immunodeficiency Virus Type 1 Confer Distinct Phenotypes That Are Discerned by Competition and Neutralization Experiments. J. Virol. 77: 8448-8461 [Abstract] [Full Text]  
  • Polonis, V. R., Souza, M. S. d., Darden, J. M., Chantakulkij, S., Chuenchitra, T., Nitayaphan, S., Brown, A. E., Robb, M. L., Birx, D. L. (2003). Human Immunodeficiency Virus Type 1 Primary Isolate Neutralization Resistance Is Associated with the Syncytium-Inducing Phenotype and Lower CD4 Cell Counts in Subtype CRF01_AE-Infected Patients. J. Virol. 77: 8570-8576 [Abstract] [Full Text]  
  • Johnston, E. R., Zijenah, L. S., Mutetwa, S., Kantor, R., Kittinunvorakoon, C., Katzenstein, D. A. (2003). High Frequency of Syncytium-Inducing and CXCR4-Tropic Viruses among Human Immunodeficiency Virus Type 1 Subtype C-Infected Patients Receiving Antiretroviral Treatment. J. Virol. 77: 7682-7688 [Abstract] [Full Text]  
  • Wei, Q., Fultz, P. N. (2002). Differential Selection of Specific Human Immunodeficiency Virus Type 1/JC499 Variants after Mucosal and Parenteral Inoculation of Chimpanzees. J. Virol. 76: 851-864 [Abstract] [Full Text]  
  • Tokunaga, K., Greenberg, M. L., Morse, M. A., Cumming, R. I., Lyerly, H. K., Cullen, B. R. (2001). Molecular Basis for Cell Tropism of CXCR4-Dependent Human Immunodeficiency Virus Type 1 Isolates. J. Virol. 75: 6776-6785 [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»