The HIV-1 Life Cycle is Blocked at Two Different Points in Mature Dendritic Cells
The proliferative status of the host cells influences the life cycle of retroviruses1,2. For oncogenic retroviruses cell division is considered a prerequisite for integration and viral replication. Lentiviruses differ from oncogenic retroviruses because they can complete their replicative cycle indipendently from cell division. The HIV-1 lentivirus uses a gag targeting cell to access the nucleus and integrate into macrophages. HIV-1 productively infects monocytes and terminally differentiated macrophages in specific organs like brain and cultured blood monocytes3,4. The predominant target for HIV-1 in the blood is a CD4+ T lymphocyte, but activation of T cells is required for productive infection. Nonetheless, HIV-1 is capable of infecting and persisting in resting T cells without producing virions5. Once infected the resting T cell can synthesize an incomplete form of viral DNA5 without complete reverse transcription. Following stimulation of the infected quiescent cells, productive infection occurs.5,6 Dendritic cells represent a distinct lineage of white cells that derive from CD34+ progenitors in the bone marrow. They are motile and widely distributed in most of the tissues and in all components of lymphoid system [for review see7]. Dendritic cells are specialized antigen-presenting cells for T cells in situ, both for self-antigens during T cell development and foreign antigens during immunity. Although relatively few in number, dendritic cells are effective antigen presenting cells because they express not only high levels of MHC class I and II but also several of the accessory molecules that are required for T cell binding and activation8,9. In many tissues dendritic cells express CD4 as in skin10, tonsil11, thymus12, and several mucosae13. Recently, methods to generate large quantities of mature dendritic cells from blood precursors have been described14.
KeywordsDendritic Cell Chemokine Receptor Productive Infection Mature Dendritic Cell Reverse Transcript
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- 6.Stevenson, M., Stanwick, T. L., Dempsey, M. P. & Lamonica, C. A. EMBO 9, 1551–1560 (1990).Google Scholar
- 7.Steinman. R. M., Schuler, G., Romani, N. & Kaplan, G. in Atlas of Blood Cells: Function and Pathology (eds Zucker-Franklin, D., Greaves, M.F., Grossi, C.E. & Marmont, A.M.) Vol.2nd, 359–377 ( Lea & Febiger, Philadelphia, PA, 1988 ).Google Scholar
- 10.Nestle, F. O., Zheng, X.-G., Thompson, C. B., Turka, L. A. & Nickoloff, B. J. J. Immunol. 151, 6535–6545 (1993).Google Scholar
- 13.Pavli, P., flume, D. A., Van de Pol, E. & Doe, W. F. Immunol. 78, 132–141 (1993).Google Scholar
- 16.Macatonia, S. E., Patterson, S. & Knight, S. C. Immunol. 67, 285–289 (1989).Google Scholar
- 17.Cameron, P. U., Lowe, M. G., Crowe, S. M., et al. J. Leuk. Biol. 56, 257–265 (1994).Google Scholar
- 26.Granelli-Piperno, A., Moser. B., Pope, M., et al. Submitted (1996).Google Scholar