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Tenofovir and dolutegravir reduce human T-cell leukemia virus 1 transmission and de novo viral spread in vivo

ABSTRACT: Human T-leukemia virus 1 (HTLV-1) is an oncogenic retrovirus with no available curative therapy. In-vitro data suggests HTLV-1 may be susceptible to certain HIV-1 antiretroviral compounds but their value, if any, in the context of a clinically-relevant transmission model is unknown. We addressed this knowledge gap by investigating the efficacy of the anti-retroviral compounds, tenofovir and dolutegravir, in preventing HTLV-1 transmission and infection in a humanised mouse model of HTLV-1 subtype c (HTLV-1c) infection, the first of its kind. Characterisation of this model revealed that HTLV-1c and HTLV-1 subtype a (HTLV-1a) showed subtle differences in natural history of disease but not as striking as the differences observed clinically, indicating additional host and environmental contributors to human disease. Single cell RNA sequencing of CD4+ T cell VDJ transcripts revealed poly- and oligoclonal expansion of HTLV-1c-infected CD4+ T cells. We show that tenofovir significantly reduces HTLV-1 transmission in vivo at clinically relevant doses when administered as pre-exposure prophylaxis. Further, tenofovir and dolutegravir combination significantly attenuates viral spread and disease progression during early infection. Our data support the use of tenofovir and dolutegravir against HTLV-1 transmission and early infection. Routine use of these drugs as effective prophylactic agents against HIV-1 infection will facilitate their rapid translation to HTLV-1 clinical trials.

ORGANISM(S): Homo sapiens

PROVIDER: GSE157492 | GEO | 2024/12/31

REPOSITORIES: GEO

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