In addition to direct transcytosis across epithelial cells, the interdigitating processes of dendritic cells that ramify between epithelial cells provide an avenue for HIV to traverse the epithelium. A complex ferrying mechanism seems to transfer HIV picked up by dendritic cells to CD4 T cells in lymphoid tissue. HIV can attach to dendritic cells by the binding of viral gp120 to Ctype lectin receptors such as langerin (CD207), the mannose receptor (CD206), and DCSIGN. A portion of the bound virus is rapidly taken up into vacuoles, where it can remain for days in an infectious state. In this way the virus is protected and remains stable until it encounters a susceptible CD4 T cell, whether in the local mucosal environment or after being carried to draining lymphoid tissue (Fig. 13.32). Finally, at some mucosal sites, CCR5expressing CD4 T cells reside within the epithelium (intraepithelial T cells), and have been shown to be sites of early viral replication. Thus, HIV can infect CD4 T cells either directly or via dendritic cells that interact with CD4 T cells.
HIV is internalized into early endosomes Dendritic cells that have migrated to lymph nodes transfer HIV to CD4 T cells Intraepithelial dendritic cells bind HIV using DC-SIGN
Fig. 13.32 Dendritic cells can initiate infection by transporting HIV from mucosal surfaces to lymphoid tissue.
During the acute phase of infection, which typically lasts for several weeks and is characterized by an influenzalike illness, there is rapid replication of the virus, primarily in CCR5expressing CD4 T cells (Fig. 13.33). This period is marked by an abundance of virus circulating in the blood (viremia) and the rapid decline of CCR5expressing CD4 T cells, the latter due primarily to the
HiV adheres to the surface of intraepithelial dendritic cells by the binding of viral gp120 to DC-SiGn (left panel). it gains access to dendritic cells at sites of mucosal injury or possibly to dendritic cells that have protruded between epithelial cells to sample the external world; HiV can also bind directly to some epithelial cells and is transported across them to subepithelial dendritic cells (not shown). Dendritic cells internalize HiV virions into mildly acidic early endosomes and migrate to lymphoid tissue (center panel). HiV virions are translocated back to the cell surface, and when the dendritic cell encounters CD4 t cells in a secondary lymphoid tissue, the HiV is transferred to the t cell (right panel).
Fig. 13.33 The typical course of untreated infection with HIV. other symptoms become more frequent as the CD4 t-cell count in the first few weeks are typified by an acute influenza-like viral illness, peripheral blood falls, starting at about 500 cells · μl–1. the disease sometimes called seroconversion disease, with high titers of virus in then enters the symptomatic phase. When CD4 t-cell counts fall the blood. an adaptive immune response follows, which controls the below 200 cells · μl–1, the patient is said to have aiDS. note that acute illness and largely restores levels of CD4 t cells but does not CD4 t-cell counts are measured for clinical purposes in cells per eradicate the virus. this is the asymptomatic phase, which typically microliter (cells · μl–1), rather than cells per milliliter (cells · ml–1), the lasts 5–10 years without treatment. Opportunistic infections and unit used elsewhere in this book.