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Published on: December 21, 2019
TF protein of Sindbis virus antagonizes host type I interferon responses in a palmitoylation-dependent manner
K J Rogers1, S Jones-Burrage2, W Maury1
1Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Abstract:
Sindbis virus (SINV) produces the small membrane protein TF from the 6K gene via a (-1) programmed ribosomal frameshifting. While several groups have shown that TF-deficient virus exhibits reduced virulence, the mechanism(s) by which this occurs remain unknown. Here, we demonstrate a role for TF in antagonizing the host interferon response. Using wild-type and type 1 interferon receptor-deficient mice and primary cells derived from these animals, we show that TF controls the induction of the host interferon response at early times during infection. Loss of TF production leads to elevated interferon and a concurrent reduction in viral loads with a loss of pathogenicity. Palmitoylation of TF has been shown to be important for particle assembly and morphology. We find that palmitoylation of TF also contributes to the ability of TF to antagonize host interferon responses as dysregulated palmitoylation of TF reduces virulence in a manner similar to loss of TF.
Insights
Sindbis virus (SINV) small membrane protein TF antagonizes the host interferon response. Loss of TF or its proper palmitoylation reduces viral pathogenicity by increasing interferon levels.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Sindbis virus (SINV) produces the small membrane protein TF from the 6K gene through programmed ribosomal frameshifting.
- TF-deficient SINV exhibits reduced virulence, but the underlying mechanisms are not fully understood.
Purpose of the Study:
- To elucidate the role of TF in viral pathogenesis.
- To investigate the mechanism by which TF influences the host interferon response and viral virulence.
Main Methods:
- Utilized wild-type and type 1 interferon receptor-deficient mice and primary cells.
- Assessed the impact of TF production and palmitoylation on host interferon induction and viral loads during SINV infection.
Main Results:
- TF antagonizes the host interferon response, controlling its induction early in infection.
- Loss of TF production leads to elevated interferon, reduced viral loads, and decreased pathogenicity.
- Palmitoylation of TF is crucial for its ability to antagonize interferon, with dysregulated palmitoylation reducing virulence.
Conclusions:
- TF plays a critical role in antagonizing the host interferon response during SINV infection.
- TF's ability to modulate interferon is linked to its palmitoylation status and overall viral pathogenicity.
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