Abstract |
Type I interferon (IFN-I) inhibits the replication of different viruses. However, the effect of IFN-I on the human T-lymphotropic virus type 1 (HTLV-1) viral cycle is controversial. Here, we investigated the consequences of IFN-α addition for different steps of HTLV-1 and HTLV-2 infection. We first show that alpha interferon (IFN-α) efficiently impairs HTLV-1 and HTLV-2 de novo infection in a T cell line and in primary lymphocytes. Using pseudotyped viruses expressing HTLV-1 envelope, we then show that cell-free infection is insensitive to IFN-α, demonstrating that the cytokine does not affect the early stages of the viral cycle. In contrast, intracellular levels of Gag, Env, or Tax protein are affected by IFN-α treatment in T cells, primary lymphocytes, or 293T cells transfected with HTLV-1 or HTLV-2 molecular clones, demonstrating that IFN-α acts during the late stages of infection. We show that IFN-α does not affect Tax-mediated transcription and acts at a posttranscriptional level. Using either small interfering RNA ( siRNA) directed against PKR or a PKR inhibitor, we demonstrate that PKR, whose expression is induced by interferon, plays a major role in IFN-α-induced HTLV-1/2 inhibition. These results indicate that IFN-α has a strong repressive effect on the HTLV-1 and HTLV-2 viral cycle during de novo infection of cells that are natural targets of the viruses.
|
Authors | Anne Cachat, Sébastien Alain Chevalier, Sandrine Alais, Nga Ling Ko, Lee Ratner, Chloé Journo, Hélène Dutartre, Renaud Mahieux |
Journal | Journal of virology
(J Virol)
Vol. 87
Issue 24
Pg. 13386-96
(Dec 2013)
ISSN: 1098-5514 [Electronic] United States |
PMID | 24089560
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Interferon alpha-2
- Interferon-alpha
- Recombinant Proteins
- EIF2AK1 protein, human
- eIF-2 Kinase
|
Topics |
- Cell Line
- Enzyme Activation
- HTLV-I Infections
(enzymology, genetics, virology)
- HTLV-II Infections
(enzymology, genetics, virology)
- Host-Pathogen Interactions
- Human T-lymphotropic virus 1
(genetics, physiology)
- Human T-lymphotropic virus 2
(genetics, physiology)
- Humans
- Interferon alpha-2
- Interferon-alpha
(metabolism)
- Recombinant Proteins
(metabolism)
- eIF-2 Kinase
(genetics, metabolism)
|