scholarly journals LRRC59 modulates type I interferon signaling by restraining the SQSTM1/p62-mediated autophagic degradation of pattern recognition receptor DDX58/RIG-I

Autophagy ◽  
2019 ◽  
Vol 16 (3) ◽  
pp. 408-418 ◽  
Author(s):  
Huifang Xian ◽  
Shuai Yang ◽  
Shouheng Jin ◽  
Yuxia Zhang ◽  
Jun Cui
2012 ◽  
Vol 9 (1) ◽  
pp. 25 ◽  
Author(s):  
Aaron Erdely ◽  
James M Antonini ◽  
Rebecca Salmen-Muniz ◽  
Angie Liston ◽  
Tracy Hulderman ◽  
...  

2020 ◽  
Vol 8 (6) ◽  
pp. 790 ◽  
Author(s):  
Markus Fabits ◽  
Vladimir Gonçalves Magalhães ◽  
Baca Chan ◽  
Virginie Girault ◽  
Endrit Elbasani ◽  
...  

The rapid activation of pattern recognition receptor (PRR)-mediated type I interferon (IFN) signaling is crucial for the host response to infection. In turn, human cytomegalovirus (HCMV) must evade this potent response to establish life-long infection. Here, we reveal that the HCMV tegument protein UL35 antagonizes the activation of type I IFN transcription downstream of the DNA and RNA sensors cGAS and RIG-I, respectively. We show that ectopic expression of UL35 diminishes the type I IFN response, while infection with a recombinant HCMV lacking UL35 induces an elevated type I IFN response compared to wildtype HCMV. With a series of luciferase reporter assays and the analysis of signaling kinetics upon HCMV infection, we observed that UL35 downmodulates PRR signaling at the level of the key signaling factor TANK-binding kinase 1 (TBK1). Finally, we demonstrate that UL35 and TBK1 co-immunoprecipitate when co-expressed in HEK293T cells. In addition, we show that a previously reported cellular binding partner of UL35, O-GlcNAc transferase (OGT), post-translationally GlcNAcylates UL35, but that this modification is not required for the antagonizing effect of UL35 on PRR signaling. In summary, we have identified UL35 as the first HCMV protein to antagonize the type I IFN response at the level of TBK1, thereby enriching our understanding of how this important herpesvirus escapes host immune responses.


2017 ◽  
Vol 68 (2) ◽  
pp. 308-322.e4 ◽  
Author(s):  
Shouheng Jin ◽  
Shuo Tian ◽  
Man Luo ◽  
Weihong Xie ◽  
Tao Liu ◽  
...  

2019 ◽  
Author(s):  
Agnès Garcias López ◽  
Vasileios Bekiaris ◽  
Katarzyna Müller Luda ◽  
Julia Hütter ◽  
Konjit Getachew Muleta ◽  
...  

AbstractInitiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design however requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity towards viruses, intracellular bacteria and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various genetic models, we show here that both the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNFα dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.


Sign in / Sign up

Export Citation Format

Share Document