VARIABLE COURSE OF PRIMARY SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION INLYMPH-NODES - RELATION TO DISEASE PROGRESSION

To investigate the dynamics of spread of simian immunodeficiency virus (SIV) in the lymphoid organs, we sequentially analyzed the viral burd en in lymph nodes (LN) of eight rhesus macaques inoculated intravenous ly with a high or low dose of the pathogenic SIVmac 251 isolate. For e ach animal, four axillary or inguinal LN were collected during the fir st weeks of infection and a fifth LN was taken 6 or 8 months later to estimate disease progression. Measurement of SIV RNA by in situ hybrid ization showed that all of the macaques studied had a phase of acute v iral replication in LN between 7 and 14 days postinoculation which par alleled that observed in the blood. In a second phase, productive infe ction was controlled and viral particles were trapped in the germinal centers that developed in LN. While the peaks of productive infection were similar for the eight animals, marked differences in the numbers of productively infected cells that persisted in LN after primary infe ction were seen. Differences were less pronounced in the blood, where productive infection was efficiently controlled in all cases. The pers istence of productively infected cells in LN after primary infection w as found to be associated with more rapid disease progression, as meas ured by the decrease of the T4/T8 ratio and the occurrence of clinical signs. However, the persistence of a significant level of viral parti cles in germinal centers was observed even in animals that remained he althy over a 1- to 2-year observation period. This study indicates tha t the course of primary SIV infection in LN is variable, and it sugges ts that the initial capacity of the host to control productive infecti on in LN may determine the rate of disease progression.