In Vivo Cytolysis and Fusion of Human Immunodeficiency Virus Type 1–Infected Lymphocytes in Lymphoid Tissue

Lymphoid tissue was examined to see whether in vivo cytopathic effects of human immunodeficiency virus (HIV) infection on lymphocytes could be detected. Transmission electron microscopy of mechanical suspensions prepared from lymph nodes showed both replication and phagocytosis of HIV particles by macrophages. Phagosomes contained cellular debris and virions, some of which were undergoing digestion. Neutrophils also contained HIV particles intermixed with cellular debris in phagosomes. Immunohistochemistry revealed whole Gag p24-positive lymphocytes and p24-positive cellular debris within the cytoplasm of paracortical macrophages. Lysing p24-positive lymphocytes were also seen. In the paracortex, p24-positive multinucleated lymphocytes with up to 5 nuclei were seen. In situ hybridization for HIV RNA in combination with immunohistochemistry for HAM56, a macrophage-specific marker, revealed colabeled cells. Thus, HIV-positive lymphocytes undergo lysis in lymphoid tissue. The cellular debris is phagocytized by macrophages, which themselves can replicate HIV. HIV-positive lymphocytes fuse in lymph nodes to form multinucleated cells.