scholarly journals Selective modulation of cell surface proteins during vaccinia infection: implications for immune evasion strategies

2021 ◽  
Author(s):  
Delphine M Depierreux ◽  
Arwen F Altenburg ◽  
Lior Soday ◽  
Alice Fletcher-Etherington ◽  
Robin Antrobus ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Nk Cell ◽  
Surface Proteins ◽  
Future Studies ◽  
Oncolytic Therapy ◽  
Viral Immune Evasion ◽  
Host Pathogen Interaction ◽  
Selective Modulation ◽  
Independent Mechanism ◽  
Host Regulation

The interaction between immune cells and virus-infected targets involves multiple plasma membrane (PM) proteins. A systematic study of PM protein modulation by vaccinia virus (VACV), the paradigm of host regulation, has the potential to reveal not only novel viral immune evasion mechanisms, but also novel factors critical in host immunity. Here, >1000 PM proteins were quantified throughout VACV infection, revealing selective downregulation of known T and NK cell ligands including HLA-C, downregulation of cytokine receptors including IFNAR2, IL-6ST and IL-10RB, and rapid inhibition of expression of certain protocadherins and ephrins, candidate activating immune ligands. Downregulation of most PM proteins occurred via a proteasome-independent mechanism. Upregulated proteins included a decoy receptor for TRAIL. Twenty VACV-encoded PM proteins were identified, of which five were not recognised previously as such. Collectively, this dataset constitutes a valuable resource for future studies on antiviral immunity, host-pathogen interaction, poxvirus biology, vector-based vaccine design and oncolytic therapy.

scholarly journals The complex of MCMV proteins and MHC class I evades NK cell control and drives the evolution of virus-specific activating Ly49 receptors

2019 ◽  
Vol 216 (8) ◽  
pp. 1809-1827 ◽  
Author(s):  
Jelena Železnjak ◽  
Vanda Juranić Lisnić ◽  
Branka Popović ◽  
Berislav Lisnić ◽  
Marina Babić ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Evasion ◽  
Nk Cell ◽  
Cytotoxic T Cells ◽  
Mhc I ◽  
Immune Evasion Mechanism ◽  
Viral Immune Evasion ◽  
Nk Cell Receptors ◽  
Self Recognition ◽  
Missing Self

CMVs efficiently target MHC I molecules to avoid recognition by cytotoxic T cells. However, the lack of MHC I on the cell surface renders the infected cell susceptible to NK cell killing upon missing self recognition. To counter this, mouse CMV (MCMV) rescues some MHC I molecules to engage inhibitory Ly49 receptors. Here we identify a new viral protein, MATp1, that is essential for MHC I surface rescue. Rescued altered-self MHC I molecules show increased affinity to inhibitory Ly49 receptors, resulting in inhibition of NK cells despite substantially reduced MHC I surface levels. This enables the virus to evade recognition by licensed NK cells. During evolution, this novel viral immune evasion mechanism could have prompted the development of activating NK cell receptors that are specific for MATp1-modified altered-self MHC I molecules. Our study solves a long-standing conundrum of how MCMV avoids recognition by NK cells, unravels a fundamental new viral immune evasion mechanism, and demonstrates how this forced the evolution of virus-specific activating MHC I–restricted Ly49 receptors.

NKp46 and DNAM-1 NK-cell receptors drive the response to human cytomegalovirus-infected myeloid dendritic cells overcoming viral immune evasion strategies

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 848-856 ◽  
Author(s):  
Giuliana Magri ◽  
Aura Muntasell ◽  
Neus Romo ◽  
Andrea Sáez-Borderías ◽  
Daniela Pende ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Human Cytomegalovirus ◽  
Immune Evasion ◽  
Nk Cell ◽  
Human Leukocyte ◽  
Myeloid Dendritic Cells ◽  
Receptor Ligand ◽  
Leukocyte Antigen ◽  
Viral Immune Evasion ◽  
Ligand Interactions

Abstract Information on natural killer (NK)–cell receptor-ligand interactions involved in the response to human cytomegalovirus (HCMV) is limited and essentially based on the study of infected fibroblasts. Experimental conditions were set up to characterize the NK response to HCMV-infected myeloid dendritic cells (DCs). Monocyte-derived DCs (moDCs) infected by the TB40/E HCMV strain down-regulated the expression of human leukocyte antigen class I molecules and specifically activated autologous NK-cell populations. NKG2D ligands appeared virtually undetectable in infected moDCs, reflecting the efficiency of immune evasion mechanisms, and explained the lack of antagonistic effects of NKG2D-specific monoclonal antibody. By contrast, DNAM-1 and DNAM-1 ligands (DNAM-1L)–specific monoclonal antibodies inhibited the NK response at 48 hours after infection, although the impact of HCMV-dependent down-regulation of DNAM-1L in infected moDCs was perceived at later stages. moDCs constitutively expressed ligands for NKp46 and NKp30 natural cytotoxicity receptors, which were partially reduced on HCMV infection; yet, only NKp46 appeared involved in the NK response. In contrast to previous reports in fibroblasts, human leukocyte antigen-E expression was not preserved in HCMV-infected moDCs, which triggered CD94/NKG2A+ NK-cell activation. The results provide an insight on key receptor-ligand interactions involved in the NK-cell response against HCMV-infected moDCs, stressing the importance of the dynamics of viral immune evasion mechanisms.

scholarly journals The Brilliance of Borrelia: Mechanisms of Host Immune Evasion by Lyme Disease-Causing Spirochetes

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 281
Author(s):  
Cassidy Anderson ◽  
Catherine A. Brissette
Keyword(s):  
Immune Response ◽  
Lyme Disease ◽  
Immune Evasion ◽  
Host Immune Response ◽  
Surface Proteins ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Adaptive Responses ◽  
Tick Saliva ◽  
Vector Borne ◽  
Antimicrobial Peptide Resistance

Lyme disease (LD) has become the most common vector-borne illness in the northern hemisphere. The causative agent, Borrelia burgdorferi sensu lato, is capable of establishing a persistent infection within the host. This is despite the activation of both the innate and adaptive immune responses. B. burgdorferi utilizes several immune evasion tactics ranging from the regulation of surface proteins, tick saliva, antimicrobial peptide resistance, and the disabling of the germinal center. This review aims to cover the various methods by which B. burgdorferi evades detection and destruction by the host immune response, examining both the innate and adaptive responses. By understanding the methods employed by B. burgdorferi to evade the host immune response, we gain a deeper knowledge of B. burgdorferi pathogenesis and Lyme disease, and gain insight into how to create novel, effective treatments.

scholarly journals Downregulation of NKG2DLs by TGF-β in human lung cancer cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Young Shin Lee ◽  
Hojung Choi ◽  
Hae-Ryung Cho ◽  
Woo-Chang Son ◽  
You-Soo Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Nk Cell ◽  
Surface Proteins ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Altered Expression ◽  
Inhibitory Molecules

Abstract Background Transforming growth factor beta (TGF-β) is a typical immuno-inhibitory cytokine and highly secreted by lung cancer cells. It was supposed that its immunosuppressive effects to NK cell might be related with the altered expression of activating and inhibitory molecules in lung cancer cells. In this study, we examined the expression of NKG2DLs, PD-L1 and PD-L2 in lung cancer cells after treatment of TGF-β and a TGF-β inhibitor, Galunisertib (LY2157299). Results TGF-β reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-β on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-β, it was thought that TGF-β induced the expression of MMP2 which facilitated the shedding of the NKG2DLs in cancer cells. However, the expression of PD-L1, L2 were not changed by treatment with TGF-β or Galunisertib. Conclusions Therefore, inhibition of TGF-β might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.

scholarly journals Structure of the Infective Getah Virus at 2.8 Å-resolution Determined by Cryo-electron Microscopy

2021 ◽  
Author(s):  
Aojie Wang ◽  
Feng Zhou ◽  
Congcong Liu ◽  
Dongsheng Gao ◽  
Ruxi Qi ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Immune Evasion ◽  
Cell Invasion ◽  
Structural Information ◽  
Host Cell Invasion ◽  
Hydrophobic Pocket ◽  
Viral Immune Evasion ◽  
Cryo Electron Microscopy ◽  
Reproductive Losses ◽  
Getah Virus

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.

New insights into the structure of the MHC class I peptide-loading complex and mechanisms of TAP inhibition by viral immune evasion proteins

2019 ◽  
Vol 113 ◽  
pp. 103-114 ◽  
Author(s):  
Patrique Praest ◽  
A. Manuel Liaci ◽  
Friedrich Förster ◽  
Emmanuel J.H.J. Wiertz
Keyword(s):  
Mhc Class I ◽  
Immune Evasion ◽  
Class I ◽  
Viral Immune Evasion ◽  
Peptide Loading
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