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Chapter 8 : Effect of HIV on Various Tissues and Organ Systems in the Host

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Abstract:

HIV infection, either directly or indirectly, can affect a wide variety of tissues in the host. This chapter reviews the major organ systems that appear to be affected by the virus. The thrombocytopenia in HIV infection results from a shorter life span of platelets, increased sequestration of platelets in the spleen, and reduced platelet formation by bone marrow megakaryocytes. The effects of HIV on the immune system, defined mostly through studies of the peripheral blood, have also been described for the lymph node. Lymphoid tissues may, in fact, be the first sites for virus replication following acute infection. The primary abnormality in HIV infection is the marked reduction in CD4 cell number and function. A great deal of information has indicated the influence of various cytokines on the activity of the immune system. Studies with CD4 cell populations have suggested that over time, the TH1 response is replaced by a TH2 response, leading to a marked reduction in cellular anti-HIV immunity. HIV has been readily isolated, even early in infection, from the central nervous system (CNS). HIV disease of the kidney, known as HIV-associated nephropathy (HIVAN), is now the third leading cause of end-stage renal disease (ESRD) in African-Americans between the ages of 20 and 64. Most cardiac conditions in HIV infection are not clinically evident, but some can have fatal outcomes. Coronary artery calcifications, as well as carotid vessel intimal thickening, have been found more commonly in patients with HIV infection.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08

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Figures

Image of Figure 8.1
Figure 8.1

A simplified version of the major cells involved in immune function in the host. Bone marrow stem cells circulating through the thymus give rise to T cells that can have helper or suppressor/cytotoxic cell functions. Monocytes or dendritic cells (antigen-presenting cells) are derived from the bone marrow and interact with T-cell subsets to present antigens to induce an immune response. B cells from bone marrow pass through the bursal equivalent in humans to evolve into B cells that produce antibodies (plasma cells). All these functions entail interactions with several different members of the immune system, particularly antigen-presenting cells. The CD4 helper cells can assist in both cell-mediated and humoral immune responses. Their separation into type 1 or type 2 cells provides some distinction in these cell types (Table 11.2). Moreover, CD4 CD25 cells have been identified with suppressor or regulatory function (see Chapter 11). The final result is a balance in both arms of the immune system with functions used in defending against incoming organisms. The complex interaction of the cytokines produced by the various immune and other cells in the body is illustrated in Figure 8.3 . Cells derived from a particular precursor cell are designated with a solid-line arrow; the influence of a cell on another cell is designated with a broken-line arrow.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.2
Figure 8.2

The earliest abnormality noted in CD4 cell function has been the inability to respond to recall antigens (e.g., tetanus and influenza), followed by a reduced proliferation to alloantigens and finally to mitogens (e.g., Phytohemagglutinin [PHA] and concanavalin A [Con A]). This progression in loss of response by CD4 cells has correlated with a more rapid progression to disease (809, 4079).

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.3
Figure 8.3

Early rendition of the complex interactions among cells in the immune system and their secreted cellular factors (cytokines). Each represents a process of checks and balances to ensure a normal functioning immune system. More recent findings add further complexity to this network system. Figure courtesy of A. Fauci.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.4
Figure 8.4

Reactive astrocytes in intragyral white matter of the cerebral hemisphere of a 25-month-old boy with AIDS and severe progressive encephalopathy. Astrocytes stain dark in this photograph. Glial fibrillary acidic protein (GFAP) avidin-biotin immunoperoxidase reaction, with light hematoxylin counterstain; magnification, ×64. Photomicrograph provided by L. Sharer. Reprinted from reference 1214 with permission.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.5
Figure 8.5

Multinucleated giant cell (arrow) and inflammatory cells surrounding a blood vessel in the brain of a 6-year-old boy with AIDS and severe progressive encephalopathy. Hematoxylin and eosin; magnification, ×555. Photomicrograph courtesy of L. Sharer.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.6
Figure 8.6

Light microscopic analyses of migration of HIV-1-infected and uninfected monocytes through a blood-brain barrier model system involving bone marrow microvascular endothelium (3480). (A) Uninfected control monocytes. (B) HIV-infected cells added to the blood-brain barrier; they attack but do not alter the bone marrow microvascular epithelial cells, and the as-trocyte portion remains intact. Lipopolysaccharide-stimulated uninfected (C) and HIV-infected (D) monocytes modify the morphology of endothelial cells, and the monocytes penetrate the barrier system. Astro-cytes are found partially detached from the membrane in sites of active monocyte transmigration; magnification, ×126,000. Reprinted from reference 3480 with permission. Copyright 1997 The American Association of Immunologists, Inc.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.7
Figure 8.7

HIV-1 maturation at basolateral surfaces of polarized epithelial cells. Vero monkey monolayer cells were grown to confluency on Millicel-HA filters and prepared for electron microscopy. All stages of virus assembly were observed from the first signs of budding (top) to the final release of progeny virions (bottom). Reprinted from reference 3367 with permission.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.8
Figure 8.8

Montage of HIV-1 particles within multinucleated and mononucleated cells in the brain of a 6-year-old boy with AIDS and severe progressive encephalopathy (same patient as in Figure 8.5 ). Several types of particles are present, including immature particles and mature particles. Other particles have an atypical morphology, which suggests that they may be defective. Scale bar, 100 nm. Reprinted from reference 2986 with permission.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.9
Figure 8.9

Relationship of nucleotide sequences of viruses isolated from the blood (B) or cerebrospinal fluid (C) of the same infected individual. Results with viruses from asymptomatic carriers (#2647, #2815), one patient with persistent generalized lymphadenopathy (#931), and one patient with AIDS (#1032) are shown. The lines at the bottom of each phylogenetic tree indicate the percentage of sequence differences for comparison. A separation of blood and brain isolates by genome sequence analyses is apparent for the symptomatic patients. Reprinted from reference 2173 with permission from Elsevier.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.10
Figure 8.10

Role of infected microglia/macrophages in neuropathogenesis.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.11
Figure 8.11

Some evidence suggests that astrocytes play an active role in inactivating toxic substances entering the CNS (3286). The cells, by interacting with macrophages and microglia, can inhibit their production of cellular products that are toxic to neurons. This toxicity can be mediated by the -methyl--aspartate receptor (NMDA-R). Thus, a balance is established by which astrocytes can either synthesize neurotoxins or remove them from the CNS (Section III.E).

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.12
Figure 8.12

HIV neuropathogenesis. It is proposed that the virus infects capillary en-dothelial cells of the brain and passes via the basolateral surface of these cells to astrocytes lining the blood-brain barrier (BBB). Infection of both these cell types leads to a breakdown in the BBB and ingress of infected T cells and macrophages. The ultimate result is an infection of other brain cells (e.g., oligodendrocytes and microglia) by HIV. Production of HIV and its viral proteins ensues, as does the release of various cytokines (e.g., TNF-α and low-molecular-weight substances). These products could lead to an interruption of cell-to-cell transmission through a blockage of neurotropic factors. Direct infection of cells, as well as high levels of viral proteins (e.g., envelope glycoproteins, Tat, and Nef) and cytokines, could lead to direct neurotoxicity through detrimental effects on the cell membrane.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.13
Figure 8.13

Histology of bowel. Colonic biopsy sample from an HIV-infected subject with chronic diarrhea and no detectable pathogens. The biopsy sample shows only mild chronic inflammation, without epithelial cell damage or acute inflammation. (Hematoxylin and eosin; original magnification, ×125. Figure provided by D. Kotler.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Image of Figure 8.14
Figure 8.14

In situ hybridization of renal biopsy sample from an HIV-infected patient showing tubular epithelial cell expression of viral mRNA (arrowheads). Magnification, ×200. Reprinted from reference 3811 with permission.

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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References

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Tables

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Table 8.1

Abnormalities of the immune system in HIV infection

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.2

Potential detrimental effect of viral proteins on immune response

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.3

Potential factors involved in HIV-induced loss of CD4 lymphocyte number and immune function

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.4

Half-life of circulating CD4and CD8 T cells

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.5

Estimated turnover rate of infected CD4 cells in HIV-infected individuals

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.6

Effect of HIV infection and HIV proteins on cytokine production

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.7

Effect of cytokines on HIV-1 replication

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.8

Features of neuropathogenesis

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.9

Surface molecules present in the nervous and immune systems

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.10

Concepts in HIV neuropathogenesis

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.11

HIV entry into the central nervous system

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.12

Recovery of HIV from CSF and brain tissues

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.13

Evidence for a neurotropic virus

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.14

Cultured brain-derived cells susceptible to HIV infection

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.15

Potential role of gp120 in HIV neuropathogenesis

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.16

Neurotoxic effects of Tat

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.17

Cytokine production in the brain

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.18

Toxic effects of TNF-α in the brain

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.19

Evidence that macrophage tropism is associated with neuropathogenesis

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.20

Role of astrocytes in the CNS

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08
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Table 8.21

Factors potentially involved in HIV pathogenesis in the bowel

Citation: Levy J. 2007. Effect of HIV on Various Tissues and Organ Systems in the Host, p 165-207. In HIV and the Pathogenesis of AIDS, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815653.ch08

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