ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity.

Anne Cachat (1) , Sandrine Alais (1) , Sébastien Alain Chevalier (1) , Chloé Journo (1) , Floriane Fusil (2) , Hélène Dutartre (1) , Adrien Boniface (1) , Nga Ling Ko (3) , Antoine Gessain (3) , Cosset François-Loïc (2) , Rodolphe Suspène (4) , Jean Pierre Vartanian (4) , Renaud Mahieux (1)

1 OR - Oncogenèse rétrovirale – Retroviral Oncogenesis
2 EVIR - Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy
3 EPVO (UMR_3569 / U-Pasteur_3) - Epidémiologie et Physiopathologie des Virus Oncogènes
4 Rétrovirologie Moléculaire

The role of innate immunity in general and of type I interferon (IFN-I) in particular in HTLV-1 pathogenesis is still a matter of debate. ADAR1-p150 is an Interferon Stimulated Gene (ISG) induced by IFN-I that can edit viral RNAs. We therefore investigated whether it could play the role of an anti-HTLV factor. We demonstrate here that ADAR1 is also expressed in the absence of IFN stimulation in activated primary T-lymphocytes that are the natural target of this virus and in HTLV-1 or HTLV-2 chronically infected T-cells. ADAR1 expression is also increased in primary lymphocytes obtained from HTLV-1 infected individuals. We show that ADAR1 enhances HTLV-1 and HTLV-2 infection in T-lymphocytes and that this proviral effect is independent from its editing activity. ADAR1 expression suppresses IFN-α inhibitory effect on HTLV-1 and HTLV-2 and acts through the repression of PKR phosphorylation. This study demonstrates that two interferon stimulated genes, i.e. PKR and ADAR1 have opposite effects on HTLV replication in vivo. The balanced expression of those proteins could determine the fate of the viral cycle in the course of infection.

Domaines: Sciences du Vivant [q-bio]

Anne Cachat, Sandrine Alais, Sébastien Alain Chevalier, Chloé Journo, Floriane Fusil, et al.. ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity.. Retrovirology, 2014, 11 (1), pp.93. ⟨10.1186/s12977-014-0093-9⟩. ⟨hal-01140475⟩