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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
HTLV-I infection in squirrel monkeys (Saïmiri sciureus) using autologous, homologous, or heterologous
M Kazanji1, J P Moreau, R Mahieux
1Unité d'Epidémiologie des Virus Oncogenes, Institut Pasteur, Paris, France.
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.
Insights
Squirrel monkeys infected with human T-cell leukemia/lymphoma virus type I (HTLV-I) show promise as a model for vaccine development. This study found no significant viral mutations, suggesting suitability for HTLV-I research.
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Human T-cell leukemia/lymphoma virus type I (HTLV-I) causes serious diseases.
- Squirrel monkeys are naturally free of simian T-cell leukemia/lymphoma virus.
- Developing effective HTLV-I vaccines and understanding pathogenesis requires suitable animal models.
Purpose of the Study:
- To assess the suitability of squirrel monkeys as a model for HTLV-I infection.
- To investigate HTLV-I infection dynamics and viral adaptation in vivo.
- To evaluate the potential for using squirrel monkeys in HTLV-I vaccine research.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) from squirrel monkeys were transformed with HTLV-I using MT-2 cells.
- Monkeys were inoculated with autologous and homologous HTLV-I-transformed T cells.
- Seroconversion, proviral DNA load, and viral env gene sequences were analyzed.
Main Results:
- Permanent HTLV-I-producing T-cell lines were established from squirrel monkeys.
- Infection with autologous and homologous cells induced seroconversion and detectable proviral DNA.
- Higher proviral loads and antibody titers were observed with homologous cell inoculation.
- Comparative sequencing revealed no significant viral adaptation or mutation in the env gene.
Conclusions:
- Squirrel monkeys can be infected with HTLV-I, developing an immune response.
- The squirrel monkey is a suitable model for evaluating HTLV-I vaccines.
- This model can aid in studying HTLV-I pathogenesis due to lack of pre-existing simian T-cell leukemia/lymphoma virus infection.
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