Faculty Opinions recommendation of A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter.

Author(s):  
Thomas Meier
2021 ◽  
Author(s):  
Aojie Wang ◽  
Feng Zhou ◽  
Congcong Liu ◽  
Dongsheng Gao ◽  
Ruxi Qi ◽  
...  

Getah virus (GETV) is a mosquito-borne pathogen that can cause a mild illness and reproductive losses in animals. Although antibodies to GETV have been found in humans, there are no reports of clinical symptom associated with GETV. However, antivirals or vaccine against GETV is still unavailable due to lack of knowledge of the structure of GETV virion. Here, we present the structure of mature GETV at a resolution of 2.8 Å with capsid protein, envelope glycoproteins E1 and E2. Glycosylation and S-acylation sites in E1 and E2 are identified. The surface-exposed glycans demonstrated their impact on the viral immune evasion and host cell invasion. The S-acylation sites strongly stabilize the virion. In addition, a cholesterol and phospholipid molecule are observed in transmembrane hydrophobic pocket, together with two more cholesterols surround the pocket. These structural information are helpful for structure-based antivirals and vaccine design.


2019 ◽  
Vol 113 ◽  
pp. 103-114 ◽  
Author(s):  
Patrique Praest ◽  
A. Manuel Liaci ◽  
Friedrich Förster ◽  
Emmanuel J.H.J. Wiertz

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 409 ◽  
Author(s):  
Liyao Deng ◽  
Qiurui Zeng ◽  
Mingshu Wang ◽  
Anchun Cheng ◽  
Renyong Jia ◽  
...  

Nuclear factor-κB (NF-κB) is an important transcription factor that induces the expression of antiviral genes and viral genes. NF-κB activation needs the activation of NF-κB upstream molecules, which include receptors, adaptor proteins, NF-κB (IκB) kinases (IKKs), IκBα, and NF-κB dimer p50/p65. To survive, viruses have evolved the capacity to utilize various strategies that inhibit NF-κB activity, including targeting receptors, adaptor proteins, IKKs, IκBα, and p50/p65. To inhibit NF-κB activation, viruses encode several specific NF-κB inhibitors, including NS3/4, 3C and 3C-like proteases, viral deubiquitinating enzymes (DUBs), phosphodegron-like (PDL) motifs, viral protein phosphatase (PPase)-binding proteins, and small hydrophobic (SH) proteins. Finally, we briefly describe the immune evasion mechanism of human immunodeficiency virus 1 (HIV-1) by inhibiting NF-κB activity in productive and latent infections. This paper reviews a viral mechanism of immune evasion that involves the suppression of NF-κB activation to provide new insights into and references for the control and prevention of viral diseases.


2014 ◽  
pp. 357-377 ◽  
Author(s):  
David C. Johnson ◽  
Grant McFadden

2015 ◽  
Vol 27 (2) ◽  
pp. 125-137 ◽  
Author(s):  
Michael L. van de Weijer ◽  
Rutger D. Luteijn ◽  
Emmanuel J.H.J. Wiertz

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yihua Zhang ◽  
Manman Li ◽  
Liuyan Li ◽  
Gui Qian ◽  
Yu Wang ◽  
...  

AbstractVirus infection may induce excessive interferon (IFN) responses that can lead to host tissue injury or even death. β-arrestin 2 regulates multiple cellular events through the G protein-coupled receptor (GPCR) signaling pathways. Here we demonstrate that β-arrestin 2 also promotes virus-induced production of IFN-β and clearance of viruses in macrophages. β-arrestin 2 interacts with cyclic GMP-AMP synthase (cGAS) and increases the binding of dsDNA to cGAS to enhance cyclic GMP-AMP (cGAMP) production and the downstream stimulator of interferon genes (STING) and innate immune responses. Mechanistically, deacetylation of β-arrestin 2 at Lys171 facilitates the activation of the cGAS–STING signaling and the production of IFN-β. In vitro, viral infection induces the degradation of β-arrestin 2 to facilitate immune evasion, while a β-blocker, carvedilol, rescues β-arrestin 2 expression to maintain the antiviral immune response. Our results thus identify a viral immune-evasion pathway via the degradation of β-arrestin 2, and also hint that carvedilol, approved for treating heart failure, can potentially be repurposed as an antiviral drug candidate.


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