Role of Mononuclear Phagocytes in the Pathogenesis of Human Immunodeficiency Virus Infection

Abstract

We have presented evidence in this review for the following: (a) Macrophages are likely the first cell infected by HIV. Recovery of HIV from macrophages has been documented in the early stages of infection in which virus isolation in T cells is unsuccessful and detectable levels of antibodies against HIV are absent. (b) Macrophages are major reservoirs for HIV during all stages of infection. Unlike the lytic infection of T cells, HIV-infected macrophages show little or no virus-induced cytopathic effects. HIV-infected macrophages persist in tissue for extended periods of time (months) with large numbers of infectious particles contained within intracytoplasmic vacuoles. (c) Macrophages are a vector for the spread of infection to different tissues within the patient and between individuals. Several studies suggest a "Trojan horse" role for HIV-infected macrophages in the dissemination of infectious particles. The predominant cell in most bodily fluids (alveolar fluid, colostrum, semen, vaginal secretions) is the macrophage. In semen, for example, the numbers of macrophages exceed those of lymphocytes by more than 20-fold. (d) Macrophages are major regulatory cells that control the pace and intensity of disease progression in HIV infection. Macrophage secretory products are implicated in the pathogenesis of CNS disease and in control of viral latency in HIV-infected T cells. This litany of events in which macrophages participate in HIV-infection in humans parallels similar observations in such animal lentivirus infections as visna-maedi or caprine arthritis-encephalitis viruses. HIV interacts with monocytes differently than with T cells. Understanding this interaction may more clearly define both the pathogenesis of HIV disease and strategies for therapeutic intervention.

Retrovirally Mediated IFN-β Transduction of Macrophages Induces Resistance to HIV, Correlated with Up-Regulation of RANTES Production and Down-Regulation of C-C Chemokine Receptor-5 Expression

“…Unlike lymphocytes, HIV-infected-macrophages do not die, they persist in tissues for long periods, and they are capable of producing large amounts of HIV. Thus, they are major reservoirs for HIV during all stages of the disease and represent an efficient vector for viral dissemination throughout the body (3). The replication of HIV in tissue macrophages has been associated with clinical manifestations, including encephalopathy (1).…”

Macrophage/Microglial Accumulation and Proliferating Cell Nuclear Antigen Expression in the Central Nervous System in Human Immunodeficiency Virus Encephalopathy

“…4 -6 The transmission of virus to the central nervous system (CNS) by macrophages during acute HIV-1 infection has been proposed to account for HIV-1 dementia complex and HIVE, even though both occur much later in the course of the disease. 7 Unchecked, an active reservoir of HIV-1 infection in the CNS would presumably promote the development of clinical dementia. Accordingly, viral load in CNS and cerebral spinal fluid correlates with the severity of dementia.…”

Human immunodeficiency virus type 1 strains in the lungs of infected individuals evolve independently from those in peripheral blood and are highly conserved in the C-terminal region of the envelope V3 loop.

“…At early stages of human immunodeficiency virus type 1 (HIV-1) infection, viral isolates from the peripheral blood of infected individuals generally grow slowly, do not induce syncytia (NSI), and are tropic for monocyte lineage cells (1). These strains are also found within macrophages at diverse tissue sites, including the lung (2), nervous system (3), and salivary glands (4,5), where they may induce a variety of clinical manifestations.…”