scholarly journals Physical Aspects of Viral Membrane Fusion

2009 ◽  
Vol 9 ◽  
pp. 764-780 ◽  
Author(s):  
Laura Wessels ◽  
Keith Weninger
Keyword(s):  
Fusion Protein ◽  
Membrane Fusion ◽  
Conformational Changes ◽  
Genetic Material ◽  
Computational Techniques ◽  
Cell Penetration ◽  
Viral Membrane ◽  
Membrane Fusion Protein ◽  
Viral Membrane Fusion

Enveloped viruses commonly employ membrane fusion during cell penetration in order to deliver their genetic material across the cell boundary. Large conformational changes in the proteins embedded in the viral membrane play a fundamental role in the membrane fusion process. Despite the tremendously wide variety of viruses that contain membranes, it appears that they all contain membrane fusion protein machinery with a remarkably conserved mechanism of action. Much of our current biochemical understanding of viral membrane fusion has been derived from high-resolution structural studies and solution-basedin vitroassays in which viruses fuse with liposomes or cells. Recently, single-particle experiments have been used to provide measurements of details not available in the bulk assays. Here we focus our discussion on the key dynamical aspects of fusion protein structure, along with some of the experimental and computational techniques presently being used to investigate viral-mediated membrane fusion.

scholarly journals Shielding and activation of a viral membrane fusion protein

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Steinar Halldorsson ◽  
Sai Li ◽  
Mengqiu Li ◽  
Karl Harlos ◽  
Thomas A. Bowden ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Membrane Fusion ◽  
Viral Membrane ◽  
Membrane Fusion Protein ◽  
Viral Membrane Fusion

scholarly journals The SARS-CoV-2 host cell membrane fusion protein TMPRSS2 is a tumor suppressor and its downregulation promotes antitumor immunity and immunotherapy response in lung adenocarcinoma

2021 ◽  
Author(s):  
Zhixian Liu ◽  
Zhilan Zhang ◽  
Qiushi Feng ◽  
Xiaosheng Wang
Keyword(s):  
Lung Cancer ◽  
Cell Membrane ◽  
Fusion Protein ◽  
Membrane Fusion ◽  
Antitumor Immunity ◽  
Host Cell Membrane ◽  
Membrane Fusion Protein ◽  
In Vivo Experiments

Abstract Background Cancer patients are susceptible to SARS-CoV-2 infection. An investigation into the association between the SARS-CoV-2 host cell membrane fusion protein TMPRSS2 and lung cancer is significant, considering that lung cancer is the leading cause of cancer death and that the lungs are the primary organ SARS-CoV-2 attacks. Methods Using five lung adenocarcinoma (LUAD) genomics datasets, we explored associations between TMPRSS2 expression and immune signatures, cancer-associated pathways, tumor progression phenotypes, and clinical prognosis in LUAD by the bioinformatics approach. We validated the findings from the bioinformatics analysis through in vitro and in vivo experiments and clinical samples we collected. Results TMPRSS2 expression levels were negatively correlated with the enrichment levels of both antitumor immune signatures and immunosuppressive signatures in LUAD. However, TMPRSS2 expression levels showed a significant positive correlation with the ratios of immune-stimulatory/immune-inhibitory signatures (CD8 + T cells/PD-L1) in LUAD. TMPRSS2 downregulation correlated with elevated activities of many oncogenic pathways in LUAD, including cell cycle, mismatch repair, p53, and extracellular matrix signaling. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor advancement, and worse survival in LUAD. In vitro and in vivo experiments validated the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1. Conclusion TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a connection between lung cancer and pneumonia caused by SARS-CoV-2 infection.

scholarly journals Single-Molecule FRET Imaging of Virus Spike–Host Interactions

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 332
Author(s):  
Maolin Lu
Keyword(s):  
Structure Function ◽  
Membrane Fusion ◽  
Single Molecule ◽  
Conformational Changes ◽  
Virus Entry ◽  
Surface Glycoprotein ◽  
Therapeutic Interventions ◽  
Spike Protein ◽  
Viral Membrane ◽  
Viral Membrane Fusion

As a major surface glycoprotein of enveloped viruses, the virus spike protein is a primary target for vaccines and anti-viral treatments. Current vaccines aiming at controlling the COVID-19 pandemic are mostly directed against the SARS-CoV-2 spike protein. To promote virus entry and facilitate immune evasion, spikes must be dynamic. Interactions with host receptors and coreceptors trigger a cascade of conformational changes/structural rearrangements in spikes, which bring virus and host membranes in proximity for membrane fusion required for virus entry. Spike-mediated viral membrane fusion is a dynamic, multi-step process, and understanding the structure–function-dynamics paradigm of virus spikes is essential to elucidate viral membrane fusion, with the ultimate goal of interventions. However, our understanding of this process primarily relies on individual structural snapshots of endpoints. How these endpoints are connected in a time-resolved manner, and the order and frequency of conformational events underlying virus entry, remain largely elusive. Single-molecule Förster resonance energy transfer (smFRET) has provided a powerful platform to connect structure–function in motion, revealing dynamic aspects of spikes for several viruses: SARS-CoV-2, HIV-1, influenza, and Ebola. This review focuses on how smFRET imaging has advanced our understanding of virus spikes’ dynamic nature, receptor-binding events, and mechanism of antibody neutralization, thereby informing therapeutic interventions.

scholarly journals Viral membrane fusion

Virology ◽  
2015 ◽  
Vol 479-480 ◽  
pp. 498-507 ◽  
Author(s):  
Stephen C. Harrison
Keyword(s):  
Membrane Fusion ◽  
Viral Membrane ◽  
Viral Membrane Fusion
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