HTLV-1 Infection and Pathogenesis: New Insights from Cellular and Animal Models

Int J Mol Sci. 2021 Jul 27;22(15):8001. doi: 10.3390/ijms22158001.

Abstract

Since the discovery of the human T-cell leukemia virus-1 (HTLV-1), cellular and animal models have provided invaluable contributions in the knowledge of viral infection, transmission and progression of HTLV-associated diseases. HTLV-1 is the causative agent of the aggressive adult T-cell leukemia/lymphoma and inflammatory diseases such as the HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Cell models contribute to defining the role of HTLV proteins, as well as the mechanisms of cell-to-cell transmission of the virus. Otherwise, selected and engineered animal models are currently applied to recapitulate in vivo the HTLV-1 associated pathogenesis and to verify the effectiveness of viral therapy and host immune response. Here we review the current cell models for studying virus-host interaction, cellular restriction factors and cell pathway deregulation mediated by HTLV products. We recapitulate the most effective animal models applied to investigate the pathogenesis of HTLV-1-associated diseases such as transgenic and humanized mice, rabbit and monkey models. Finally, we summarize the studies on STLV and BLV, two closely related HTLV-1 viruses in animals. The most recent anticancer and HAM/TSP therapies are also discussed in view of the most reliable experimental models that may accelerate the translation from the experimental findings to effective therapies in infected patients.

Keywords: ATL; BLV; CIITA; CRISPR; HAM/TSP; HBZ; HTLV; NF-κB; STLV; Tax; humanized mice; restriction factors.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal*
  • HTLV-I Infections* / metabolism
  • HTLV-I Infections* / pathology
  • HTLV-I Infections* / therapy
  • Human T-lymphotropic virus 1* / metabolism
  • Human T-lymphotropic virus 1* / pathogenicity
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell* / metabolism
  • Leukemia-Lymphoma, Adult T-Cell* / pathology
  • Leukemia-Lymphoma, Adult T-Cell* / therapy
  • Mice
  • Mice, Transgenic