EARLY STAGES OF SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION IN LYMPH-NODES - EVIDENCE FOR HIGH VIRAL LOAD AND SUCCESSIVE POPULATIONS OF TARGET-CELLS

Lymph nodes obtained from 14 macaques sacrificed at early time points following experimental inoculation with simian immunodeficiency virus were analyzed by in situ hybridization for virus load and virus cellul ar tropism. The lymph nodes presented a remarkably high viral load dur ing the early phase of infection, as viral RNA was detected in as many as 2% of lymph node cells 1 week after inoculation. At this stage, ma crophages and T4 lymphocytes were identified by combined immunohistoch emistry and in situ hybridization as the target cells of the virus. Si mian immunodeficiency virus-positive macrophages concentrated in the s ubcapsular sinuses, suggesting an entry of infected cells via the affe rent lymphatics. A shift in the pattern of viral infection was observe d at 2 weeks after inoculation, with a concentration of viral RNA in t he germinal centers of the developing lymphoid follicles. Follicular d endritic cells were found to be the major target of the virus at this stage. Follicular dendritic cells were associated with high levels of viral RNA but little or no detectable viral DNA, suggesting that the v irus was present mostly in the form of viral particles trapped at the cell surface. Follicular dendritic cell-associated virus persisted at high levels for 2 months before subsiding, indicating that follicular dendritic cells constituted a major reservoir of the virus during the early stages of simian immunodeficiency virus infection