The HIV-1 Life Cycle is Blocked at Two Different Points in Mature Dendritic Cells

Abstract

The proliferative status of the host cells influences the life cycle of retroviruses^1,2. 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 monocytes^3,4. 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 activation^8,9. 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.