HTLV-I Infection in Squirrel Monkeys (Saı̈miri sciureus) Using Autologous, Homologous, or Heterologous HTLV-I-Transformed Cell Lines

Abstract

Peripheral blood mononuclear cells (PBMC) from three adult male squirrel monkeys (Saïmiri sciureus) were transformed by human T-cell leukemia/lymphoma virus type I (HTLV-I) by cocultivation with lethally irradiated human MT-2 cells. Three permanent monkey T-cell lines producing HTLV-I were obtained and characterized. Six weeks after inoculation seroconversion was observed in three of three monkeys inoculated with autologous transformed T cells and in two of three monkeys receiving homologous cells. Proviral DNA was detected in their PBMC at various times after inoculation, with the highest proviral load and antibody titers being found in monkeys infected with homologous cells. Monkeys inoculated with heterologous MT-2 cells did not seroconvert, and HTLV-I provirus was detected only transiently in their PBMC. To determine whether in vitro and in vivo HTLV-I infection of squirrel monkey cells led to a selection of monkey-adapted viral mutants, comparative sequencing of the proviral gp21 env between ex vivo monkey HTLV-I-infected PBMC, the inoculum, and MT-2 cells was done and no significant differences were detected. The squirrel monkey, which is naturally free of simian T-cell leukemia/ lymphoma virus, thus appears to be a suitable model for evaluating HTLV-I candidate vaccines and for studying the pathogenesis of HTLV-I.

Molecular and cellular aspects of HTLV-1 associated leukemogenesis in vivo

“…Analyzing the HTLV-1 replication pattern over time in PBMCs and various organs from HTLV-1 experimentally infected monkeys revealed that PBMCs and lymphoid organs constitute the major reservoirs for HTLV-1. [50][51][52][53] A pattern of persistent clonal expansion of infected cells, identical to that observed in humans, was evidenced in the PBMCs of experimentally infected animals. 51 The dissemination of the virus throughout the different body compartments appeared to result from the cellular transport of the integrated provirus.…”

Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

“…Recently, the squirrel monkey has been established as an experimental model of HTLV-1 infection. Peripheral lymphocytes, spleen, and lymph nodes were verified as major reservoirs for HTLV-1 virus during the early phase of infection (Kazanji et al, 1997Kazanji, 2000). It was subsequently established that similar to humans, HTLV-1 infection in squirrel monkeys begins through reverse transcription of the virus genome, which is then followed by clonal expansion of infected cells (Mortreux et al, 2001a).…”

HTLV-1 tropism and envelope receptor

“…HTLV-1 infection and spreading has also been closely examined after intravenous inoculation of adult squirrel monkeys (Saimiri sciureus) (Kazanji et al, 1997(Kazanji et al, , 2000Mortreux et al, 2001). In this model, peripheral blood mononuclear cells were the main infected cell compartment, but other HTLV-1-infected tissues including salivary and thyroid glands, lung, liver, pancreas, intestine, muscle and spinal cord were sporadically detected in individual monkeys (Kazanji et al, 2000).…”