Page 17 - AIDSBK23C

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surface receptors and are thus susceptible to HIV infection, mainly via CCR5. Once prMCs
reach their target tissue destination, maturation to mast cells results in loss of these surface
chemokine coreceptors and loss of susceptibility to HIV infection.[71]
B-lymphocytes may assist early spread of HIV following infection. B cells express the
complement receptor CR2 (CD21). Virions can bind to this receptor.[62]
Macrophages and dendritic (Langerhans) cells in epithelial tissues of the body, such as
the genital tract, are also important as both reservoirs and vectors for spread of HIV in the body.
Macrophages originate from blood monocytes and give rise to the body's mononuclear
phagocyte system. Langerhans cells (a subset of blood dendritic cells) originate in bone marrow
and migrate to peripheral epithelial locations in skin and mucus membranes, acting as antigen
presenting cells for lymphocytes. Dendritic cells can cross endothelium and circulate freely into
both lymphoid and mucosal tissues. HIV can be replicated within dendritic cells for up to 45
days.[72]
Both macrophages and Langerhans cells can be HIV-infected but are not destroyed.
Dendritic cells can capture HIV in their processes, providing a focus for infection of other cells.
In experimental cell cultures, the two pathways of HIV-1 spread are: (1) fluid-phase diffusion of
cell-free virions, and (2) cell–cell spread of virus. The latter is potentially more efficient, and
this is likely the case in vivo. Cell-cell transfer can include budding with fusion of closely
opposed cell membranes occurs as well as cell-cell fusion to give syncytia. Viral particles may
undergo endocytosis, may be stored in a cell surface-accessible compartment, or just directly
infect a cell via receptors. Though long-term transmission of HIV from dendritic cells to CD4
cells can be the result of active infection of the dendritic cells rather than just trapping and
presenting virion, short-term transmission occurs principally through cell surface HIV
interaction. There are pockets of plasma membrane that harbor virions on dendritic cells that
provide the means to present virions to CD4 cells via a so-called "infectious synapse."[73]
When HIV is carried to sites in the body, particularly to regional lymph nodes and to gut-
associated lymphoid tissue (GALT), the antigen-presenting cells such as macrophages or
dendritic cells act as a "Trojan horse".[74] Macrophages proliferating in response to other
infections, such as mycobacterial infections, may increase this reservoir capacity and promote
progression of HIV infection.[75] Macrophages may replicate virions on their cytoplasmic
membranes, including Golgi apparatus, and if virions are limited to intracellular compartments,
they are not seen by the immune system.[31] Langerhans cells can become infected with HIV,
even at sites distant from initial infection and during primary infection.[76]
In the host, HIV continues to replicate, mainly within lymphoid tissues. Germinal centers
of lymph nodes and GALT contain many follicular dendritic cells (FDCs). Such FDCs not only
have CD4 receptors on surface membranes, but also a surface protein, CD-SIGN, to which HIV
envelope protein can bind. The FDCs can accumulate high numbers of HIV virions, acting as
virion "warehouses".[77] Any CD4 lymphocytes percolating through the germinal centers of
lymph nodes may become infected through contact with FDCs harboring HIV virions on their
surfaces. Budding of viral particles from their surfaces indicates that productive infection of
FDCs also occurs.[78] The virions can become trapped in the interdendritic spaces of FDCs, or
they may even undergo receptor-mediated endocytosis to become localized within the FDCs, and
may escape to reside freely within the FDC cytoplasm, providing a significant reservoir of HIV
infection. The FDCs proliferate in response to early HIV infection, leading to
lymphadenopathy.[51,54,60,79]