This Article Full Text (PDF) Other Versions of this Article: JVI.00381-07v1 81/22/12582    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, P. Articles by Chen, B. K. Search for Related Content PubMed PubMed Citation Articles by Chen, P. Articles by Chen, B. K.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.00381-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Predominant mode of HIV transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses

Department of Pharmacology and Biological Chemistry, Center for Immunobiology, Mount Sinai School of Medicine, New York, NY 10029

^* To whom correspondence should be addressed. Email: ben.chen{at}mssm.edu.

	Abstract

Cell-free HIV-1 can initiate infections, but contact between infected and uninfected T cells can enhance viral spread through intercellular structures called virological synapses (VS). The relative contribution of VS versus cell-free viral transfer has not been carefully measured. Using an ultrasensitive, fluorescent virus transfer assay, we estimate that when virological synapses between HIV-expressing Jurkat T cells and primary CD4⁺ T cells are formed, cell-associated transfer of virus is 18,000-fold more efficient than uptake of cell-free virus. Furthermore, in contrast to cell-free virus uptake, the VS deposits virus rapidly into focal, trypsin-resistant compartments in target T cells. This massive virus internalization requires Env-CD4 receptor interactions, but is resistant to inhibition by patient-derived neutralizing antisera that inhibit homologous cell-free virus. Deleting the Env cytoplasmic tail does not abrogate VS-mediated transfer, but renders the VS sensitive to neutralizing antibodies, suggesting that the tail limits exposure of VS-neutralizing epitopes on the surface of infected cells. Dynamic live imaging of the VS reveals that HIV-expressing cells are polarized and make sustained, Env-dependent contacts with target cells through uropod-like structures. The polarized T cell morphology, Env-CD4 coordinated adhesion and viral transfer from HIV-infected to uninfected cells suggest that VS may allow HIV-1 to evade antibody neutralization and to disseminate efficiently. Future studies will discern to what extent this massive viral transfer contributes to productive infection or viral dissemination through the migration of virus-carrying T cells.

This article has been cited by other articles:

• Vasiliver-Shamis, G., Tuen, M., Wu, T. W., Starr, T., Cameron, T. O., Thomson, R., Kaur, G., Liu, J., Visciano, M. L., Li, H., Kumar, R., Ansari, R., Han, D. P., Cho, M. W., Dustin, M. L., Hioe, C. E. (2008). Human Immunodeficiency Virus Type 1 Envelope gp120 Induces a Stop Signal and Virological Synapse Formation in Noninfected CD4+ T Cells. J. Virol. 82: 9445-9457 [Abstract] [Full Text]  
• Ruggiero, E., Bona, R., Muratori, C., Federico, M. (2008). Virological Consequences of Early Events following Cell-Cell Contact between Human Immunodeficiency Virus Type 1-Infected and Uninfected CD4+ Cells. J. Virol. 82: 7773-7789 [Abstract] [Full Text]  
• Duval, M., Posner, M. R., Cavacini, L. A. (2008). A Bispecific Antibody Composed of a Nonneutralizing Antibody to the gp41 Immunodominant Region and an Anti-CD89 Antibody Directs Broad Human Immunodeficiency Virus Destruction by Neutrophils. J. Virol. 82: 4671-4674 [Abstract] [Full Text]  
• Groot, F., Welsch, S., Sattentau, Q. J. (2008). Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood 111: 4660-4663 [Abstract] [Full Text]  
• Hubner, W., Chen, P., Portillo, A. D., Liu, Y., Gordon, R. E., Chen, B. K. (2007). Sequence of Human Immunodeficiency Virus Type 1 (HIV-1) Gag Localization and Oligomerization Monitored with Live Confocal Imaging of a Replication-Competent, Fluorescently Tagged HIV-1. J. Virol. 81: 12596-12607 [Abstract] [Full Text]