| First Author | Cooney JP | Year | 2025 |
| Journal | Cell | Volume | 188 |
| Issue | 18 | Pages | 4896-4912.e19 |
| PubMed ID | 40645177 | Mgi Jnum | J:386158 |
| Mgi Id | MGI:8242901 | Doi | 10.1016/j.cell.2025.06.023 |
| Citation | Cooney JP, et al. (2025) Combination antiretroviral therapy and MCL-1 inhibition mitigate HTLV-1 infection in vivo. Cell 188(18):4896-4912.e19 |
| abstractText | This study investigated preventative and therapeutic agents against human T cell lymphotropic virus type-1 subtype-C (HTLV-1c) infection. We established and characterized a humanized mouse model of HTLV-1c infection and identified that HTLV-1c disease appears slightly more aggressive than the prevalent HTLV-1 subtype-A (HTLV-1a), which may underpin increased risk for infection-associated pulmonary complications in HTLV-1c. Combination antiretroviral therapy with tenofovir and dolutegravir at clinically relevant doses significantly reduced HTLV-1c transmission and disease progression in vivo. Single-cell RNA sequencing (scRNA-seq) and intracellular flow cytometry identified that HTLV-1c infection leads to dysregulated intrinsic apoptosis in infected cells in vivo. Pharmacological inhibition using BH3 mimetic compounds against MCL-1, but not BCL-2, BCL-XL, or BCL-w, killed HTLV-1c-infected cells in vitro and in vivo and significantly delayed disease progression when combined with tenofovir and dolutegravir in mice. Our data suggest that combination antiretroviral therapy with MCL-1 antagonism may represent an effective, clinically relevant, and potentially curative strategy against HTLV-1c. |
