HIV IS TRAPPED AND MASKED IN THE CYTOPLASM OF LYMPH-NODE FOLLICULAR DENDRITIC CELLS

To gain further insight into the pathogenesis of human immunodeficienc y virus (HIV) infection, lymph nodes from seven asymptomatic HIV+ subj ects were analyzed during the latent phase of disease. Both ultrastruc tural and immunohistochemical analyses revealed that, in all of the ca ses, plasma cells producing IgM/lambda were present in germinal center s. Secreted immunoglobulins formed extracellular deposits mimicking th e follicular dendritic cell network. Immunoglobulin produced by germin al center plasma cells are specific for HIV because they bind the HIV env protein gp120. Plasma cells producing antibodies with the same spe cificity were also abundant in the extrafollicular regions of lymph no nes. During the latent phase of infection, the virus largely accumulat es within the germinal centers. Therefore, extracellular immunoglobuli n may form immune complexes, as shown by the presence of HIV-specific antibodies, HIV particles, and complement components C3c, C3d, and C1q in the interdendritic spaces. When the ultrastructural localization o f HIV in germinal centers was analyzed abundant virus particles were f ound in the interdendritic spaces. In addition to this extracellular l ocalization of HIV, receptor-mediated endocytosis of viral particles b y follicular dendritic cells was observed. Complete HIV particles were found within the endosomal compartment of the follicular dendritic ce lls and as complete viral particles, free in the cytoplasm, indicating that the virus may escape front the endocytic compartment. As the vir us is abundant in the cytoplasm, this event leads to formation of a hi dden reservoir within follicular dendritic cells. In this location, HI V escapes recognition by cytotoxic T lymphocytes. In contrast, virus b udding indicating a productive infection of follicular dendritic cells that would render them susceptible to T-cell-mediated lysis has been seldom observed.