Dynamics of HIV Infection
After initial entry of HIV and establishment of infection, replication may at first occur within inflammatory cells at the site of infection or within peripheral blood mononuclear cells, but then the major site of replication quickly shifts to lymphoid tissues of the body, including those in lymph nodes, spleen, liver, and bone marrow. Besides lymph nodes, the gut associated lymphoid tissue provides a substantial reservoir for HIV.
Macrophages and Langerhans cells in epithelia such as in the genital tract are important both as reservoirs and vectors for the spread of HIV in the body. Langerhans cells (a subset of blood dendritic cells) act as antigen presenting cells for CD4 lymphocytes. Both macrophages and Langerhans cells can be HIV-infected but are not destroyed themselves. HIV can then be carried elsewhere in the body. Within lymph nodes, HIV virions are trapped in the processes of follicular dendritic cells (FDC's), where they may infect CD4 lymphocytes that are percolating through the node. The FDC's themselves become infected, but are not destroyed.
Viral replication is stimulated by a variety of cytokines such as interleukins and tumor necrosis factor which activate CD4 lymphocytes and make them more susceptible to HIV infection. Primary HIV infection is followed by a burst of viremia in which virus is easily detected in peripheral blood in mononuclear cells and plasma. In the period of clinical latency of HIV infection, there is little detectable virus in peripheral blood, but viral replication actively continues in lymphoid tissues.
Subsets of the CD4+ lymphocyte population are important in determining the host response to infection. The subset known as TH1 (T helper 1) is responsible for directing a cytotoxic CD8 lymphocyte (CTL) response, but the TH2 (T helper 2) subset of CD4 and CD8 T-lymphocytes diminishes the CTL response while increasing antibody production. HIV-infectons accompanied by a dominant TH1 response tend to proceed longer. The switch from a TH1 to a TH2 response has been suggested as a factor in the development of AIDS, but not all cytokines in HIV-infected persons at different stages of disease corroborate this hypothesis. Production of interleukin-5 and interferon-gamma by CD4 and CD8 lymphocytes expressing CD30, however, is associated with promotion of B-lymphocyte immunoglobulin production.
Macrophages and Langerhans cells in epithelia such as in the genital tract are important both as reservoirs and vectors for the spread of HIV in the body. Langerhans cells (a subset of blood dendritic cells) act as antigen presenting cells for CD4 lymphocytes. Both macrophages and Langerhans cells can be HIV-infected but are not destroyed themselves. HIV can then be carried elsewhere in the body. Within lymph nodes, HIV virions are trapped in the processes of follicular dendritic cells (FDC's), where they may infect CD4 lymphocytes that are percolating through the node. The FDC's themselves become infected, but are not destroyed.
Viral replication is stimulated by a variety of cytokines such as interleukins and tumor necrosis factor which activate CD4 lymphocytes and make them more susceptible to HIV infection. Primary HIV infection is followed by a burst of viremia in which virus is easily detected in peripheral blood in mononuclear cells and plasma. In the period of clinical latency of HIV infection, there is little detectable virus in peripheral blood, but viral replication actively continues in lymphoid tissues.
Subsets of the CD4+ lymphocyte population are important in determining the host response to infection. The subset known as TH1 (T helper 1) is responsible for directing a cytotoxic CD8 lymphocyte (CTL) response, but the TH2 (T helper 2) subset of CD4 and CD8 T-lymphocytes diminishes the CTL response while increasing antibody production. HIV-infectons accompanied by a dominant TH1 response tend to proceed longer. The switch from a TH1 to a TH2 response has been suggested as a factor in the development of AIDS, but not all cytokines in HIV-infected persons at different stages of disease corroborate this hypothesis. Production of interleukin-5 and interferon-gamma by CD4 and CD8 lymphocytes expressing CD30, however, is associated with promotion of B-lymphocyte immunoglobulin production.
