HTLV-1 Infection of Humanized NOD/SCID IL2 γc−/− and BALB/c-Rag2−/−γc−/− Mouse Models

The field of animal models for biomedical research has greatly benefited from the emergence of human immune system (HIS) mice. These “humanized” mice, which are sustainably engrafted with a HIS, have significantly contributed in delineating and recapitulating the immuno-pathogenesis of human infectious diseases, specifically of human lymphotropic infections, such as HIV, HTLV-1, and EBV. In this chapter, a special attention is given to HTLV-1 (Human T-cell lymphotropic virus type 1), the causative agent of adult T-cell leukemia/lymphoma (ATLL), and of inflammatory diseases such as the tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Recent studies performed with humanized NOD/SCID IL2γ chain null (γc−/−) and BALB/c-Rag2−/−γc−/− have shown that these HIS mice are efficiently and persistently infected by HTLV-1. Interestingly, several months after infection, CD4+ T-cell lymphomas with characteristics of ATLL developed in these mice. Furthermore, the proliferation of activated human CD4+ T lymphocytes has been observed in the peripheral blood and peripheral organs, as a consequence of the early infection of progenitors in the bone marrow and/or in the thymus. As such, these HIS mice provide appropriate models for the characterization of molecular and cellular events that control the initiation and progression of the leukemogenic process. They therefore represent promising preclinical tools to investigate new therapeutic approaches against HTLV-1 associated diseases.