Lymphoid organs as a major reservoir for human T-cell leukemia virus type 1 in experimentally infected squirrel monkeys (Saimiri sciureus): Provirus expression, persistence, and humoral and cellular immune responses

The aim of this study was to investigate the distribution of human T-cell l eukemia virus type 1 (HTLV-1) in various organs of serially sacrificed squi rrel monkeys (Saimiri sciureus) in order to localize the reservoir of the v irus and to evaluate the relationship between viral expression and the humo ral or cellular immune response during infection. Six squirrel monkeys infe cted with HTLV-1 were sacrificed 6, 12, and 35 days and 3, 6, and 26 months after inoculation and 20 organs and tissues were collected from each anima l, PCR and reverse transcription-PCR (RT-PCR) were performed with gag and t ar primers. Proviral DNA was detected by PCR in peripheral blood mononuclea r cells (PBMCs) of monkeys sacrificed 6 days after inoculation and in PBMCs , spleens, and lymph nodes of monkeys sacrificed 12 and 35 days and 3, 6, a nd 26 months after inoculation. Furthermore, tar/rex mRNA was detected by R T-PCR in the PBMCs of two monkeys 8 to 12 days after inoculation and in the spleens and lymph nodes of the monkey sacrificed on day 12, in this animal , scattered HTLV-1 tax/rex mRNA-positive lymphocytes were detected by in si tu hybridization in frozen sections of the spleen, around the germinal cent ers and close to the arterial capillaries. Anti-HTLV-1 tell-mediated immuni ty was evaluated at various times after inoculation. Anti-p40(Tax) and anti -Env cytolytic T-cell responses were detected 2 months after infection and remained detectable thereafter. When Tax peptides were used, this response appeared to be directed against various Tax epitopes, Our results indicate that squirrel monkeys represent a promising animal model for studying the e arly events of HTLV-1 infection and for evaluating candidate vaccines again st HTLV-1.