title: Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage.
abstract: Human immunodeficiency virus type 1 (HIV-1) has been shown to replicate productively in cells of the monocyte-macrophage lineage, although replication occurs to a lesser extent than in infected T cells. As cells of the monocyte-macrophage lineage become differentiated and activated and subsequently travel to a variety of end organs, they become a source of infectious virus and secreted viral proteins and cellular products that likely initiate pathological consequences in a number of organ systems. During this process, alterations in a number of signaling pathways, including the level and functional properties of many cellular transcription factors, alter the course of HIV-1 long terminal repeat (LTR)-directed gene expression. This process ultimately results in events that contribute to the pathogenesis of HIV-1 infection. First, increased transcription leads to the upregulation of infectious virus production, and the increased production of viral proteins (gp120, Tat, Nef, and Vpr), which have additional activities as extracellular proteins. Increased viral production and the presence of toxic proteins lead to enhanced deregulation of cellular functions increasing the production of toxic cellular proteins and metabolites and the resulting organ-specific pathologic consequences such as neuroAIDS. This article reviews the structural and functional features of the cis-acting elements upstream and downstream of the transcriptional start site in the retroviral LTR. It also includes a discussion of the regulation of the retroviral LTR in the monocyte-macrophage lineage during virus infection of the bone marrow, the peripheral blood, the lymphoid tissues, and end organs such as the brain. The impact of genetic variation on LTR-directed transcription during the course of retrovirus disease is also reviewed.
authors.affiliation: Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 245 N 15th St, Philadelphia, Pennsylvania 19102, USA.
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Kilareski
authors.forename: Sonia
authors.initials: S
authors.lastname: Shah
authors.forename: Michael R
authors.initials: MR
authors.lastname: Nonnemacher
authors.forename: Brian
authors.initials: B
authors.lastname: Wigdahl
mesh_terms: D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D009000:Monocytes / Q000378:metabolism* / Q000821:virology; D015398:Signal Transduction; D014158:Transcription, Genetic; D014774:Virulence; D014779:Virus Replication