scholarly journals Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy

2020 ◽  
Author(s):  
Long Yang ◽  
Tingting Geng ◽  
Guang Yang ◽  
Jinzhu Ma ◽  
Leilei Wang ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Scavenger Receptor ◽  
Type I ◽  
Chikv Infection ◽  
Viral Loads ◽  
Macrophage Scavenger Receptor ◽  
Modified Low Density Lipoproteins ◽  
Wd40 Domain ◽  
Antiviral Role ◽  
Increased Susceptibility

AbstractMacrophage scavenger receptor 1 (MSR1) mediates the endocytosis of modified low-density lipoproteins and plays an important antiviral role. However, the molecular mechanism underlying MSR1 antiviral actions remains elusive. Herein, we report that MSR1 activates autophagy to restrict infection of Chikungunya virus (CHIKV), an arthritogenic alphavirus that causes acute and chronic crippling arthralgia. Msr1 expression was rapidly upregulated after CHIKV infection in mice. Msr1 knockout mice had elevated viral loads and increased susceptibility to CHIKV arthritis along with a normal type I IFN response. Induction of LC3 lipidation by CHIKV, a marker of autophagy, was reduced in Msr1-/- cells. Mechanistically, MSR1 interacted with ATG12 through its cytoplasmic tail and this interaction was enhanced by CHIKV nsP1 protein. MSR1 repressed CHIKV replication through ATG5-ATG12-ATG16L1 and this was dependent on the FIP200-and-WIPI2-binding domain, but not the WD40 domain of ATG16L1. Our results elucidate an antiviral role for MSR1 involving the autophagic function of ATG5-ATG12-ATG16L1.

scholarly journals Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Long Yang ◽  
Tingting Geng ◽  
Guang Yang ◽  
Jinzhu Ma ◽  
Leilei Wang ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Scavenger Receptor ◽  
Type I ◽  
Chikv Infection ◽  
Viral Loads ◽  
Macrophage Scavenger Receptor ◽  
Modified Low Density Lipoproteins ◽  
Wd40 Domain ◽  
Antiviral Role ◽  
Increased Susceptibility

Abstract Macrophage scavenger receptor 1 (MSR1) mediates the endocytosis of modified low-density lipoproteins and plays an important antiviral role. However, the molecular mechanism underlying MSR1 antiviral actions remains elusive. We report that MSR1 activates autophagy to restrict infection of Chikungunya virus (CHIKV), an arthritogenic alphavirus that causes acute and chronic crippling arthralgia. Msr1 expression was rapidly upregulated after CHIKV infection in mice. Msr1 knockout mice had elevated viral loads and increased susceptibility to CHIKV arthritis along with a normal type I IFN response. Induction of LC3 lipidation by CHIKV, a marker of autophagy, was reduced in Msr1−/− cells. Mechanistically, MSR1 interacted with ATG12 through its cytoplasmic tail and this interaction was enhanced by CHIKV nsP1 protein. MSR1 repressed CHIKV replication through ATG5-ATG12-ATG16L1 and this was dependent on the FIP200-and-WIPI2-binding domain, but not the WD40 domain of ATG16L1. Our results elucidate an antiviral role for MSR1 involving the autophagic function of ATG5-ATG12-ATG16L1.

scholarly journals Overproduction of IL-6 and Type-I IFN in a Lethal Case of Chikungunya Virus Infection in an Elderly Man During the 2017 Italian Outbreak

2018 ◽  
Vol 5 (11) ◽  
Author(s):  
Francesca Colavita ◽  
Serena Vita ◽  
Eleonora Lalle ◽  
Fabrizio Carletti ◽  
Licia Bordi ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Strong Increase ◽  
Type I ◽  
Type I Ifn ◽  
Chikv Infection ◽  
Clinical Presentations ◽  
Abnormal Pattern ◽  
Disease Analysis

Abstract Chikungunya fever is caused by Chikungunya virus (CHIKV) and is generally considered a self-limiting disease. However, severe clinical presentations with a high mortality rate have been reported in association with underlying medical conditions. This study reports the molecular characterization of the virus and an abnormal pattern of circulating cytokines in a unique lethal CHIKV case during the 2017 outbreak in Italy, which involved an elderly patient with underlying cardiac disease. Analysis of inflammatory cytokines revealed a strong increase of interferon (IFN)-α and IFN-β, as well as interleukin-6, suggesting a possible role of type-I IFN in the cytokine storm, which may be correlated with unfavorable prognosis of CHIKV infection.

scholarly journals CD36 in atherosclerosis

2013 ◽  
Vol 9 (1) ◽  
pp. 47-50
Author(s):  
Dhruba Acharya
Keyword(s):  
Retinal Pigment ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Cell Types ◽  
Type I ◽  
Microvascular Endothelium ◽  
Major Band ◽  
Anionic Phospholipids ◽  
Macrophage Scavenger Receptor

CD36 was described nearly 30 years ago as “glycoprotein IV” the fourth major band of 88KD observed on SDS-PAGE of platelet membrane (1). It is present on many mammalian cell types: microvascular endothelium; professional phagocytes including macrophages, dendritic cells, microglia and retinal pigment-epithellium; erythroid precursors; hepatocytes; adipocytes; cardiac and skeletal myocytes; and specialized epithelia of the breast, kidney and gut (2). As a pattern recognition receptor, CD36 binds a diverse set of ligands, including oxidized low-density lipoprotein (oxLDL)(5), anionic phospholipids (4), long-chain fatty acids, thrombospondin-1, fibrillar -amyloid, and the membrane of cells undergoing apoptosis (3, 5, 6). CD36 has been implicated in a wide variety of normal and pathologic biological functions, including angiogenesis, atherosclerosis, phagocytosis, inflammation, lipid metabolism, and removal of apoptotic cells (3, 5). In 1993, Endemann et al. first identified CD36 as a potential oxLDL receptor (7).Unlike macrophage scavenger receptor A type I and II, CD36 binds LDL that has been exposed to minimally oxidizing condition. The observation that CD36 was an oxLDL receptor was the catalyst for many to prove the role of CD36 in atherosclerosis. DOI: http://dx.doi.org/10.3126/njh.v9i1.8349 Nepalese Heart Journal Vol.9(1) 2012 pp.47-50

scholarly journals Pathogenetic Potential Relating to Metabolic Activity in a Mouse Model of Infection with the Chikungunya Virus East/Central/South African Genotype

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 169
Author(s):  
Mya Myat Ngwe Tun ◽  
Rohitha Muthugala ◽  
Aung Kyaw Kyaw ◽  
Satoshi Shimada ◽  
Kouichi Morita ◽  
...  
Keyword(s):  
South African ◽  
Metabolic Activity ◽  
Chikungunya Virus ◽  
Type I ◽  
Pathogenic Potential ◽  
East Central ◽  
Viral Loads ◽  
Central Nervous Systems ◽  
Mouse Model Of Infection ◽  
Central South

Epidemics of the Chikungunya virus (CHIKV) from 2004 onwards were caused by the East/Central/South African (ECSA) genotype. However, the pathogenesis of the genotype infection has not been fully explained. In this study, we examined the pathogenic potential of CHIKV ECSA genotype M-30 (M-30) by comparing it with that of African genotype S-27 (S-27) in mice. Following low titer infections in type-I IFN receptor KO (A129) mice, we found that the M-30 infection caused high and acute fatality compared with the S-27 infection. M-30-infected A129 mice showed higher viral loads in their central nervous systems and peripheral organs, and increased levels of IFN-γ responses in their brains. Interestingly, M-30-infected mice did not show the hypophagia and reductions in weight which were observed in S-27-infected mice. Our observations provide a novel explanation of the pathogenic mechanisms attributed to virus proliferation, anti-type-II IFN response and metabolic activity in the CHIKV ECSA virus in mice.

scholarly journals Distinct Roles of Interferon Alpha and Beta in Controlling Chikungunya Virus Replication and Modulating Neutrophil-Mediated Inflammation

2019 ◽  
Vol 94 (1) ◽  
Author(s):  
Lindsey E. Cook ◽  
Marissa C. Locke ◽  
Alissa R. Young ◽  
Kristen Monte ◽  
Matthew L. Hedberg ◽  
...  
Keyword(s):  
Immune Response ◽  
Chikungunya Virus ◽  
Biological Activities ◽  
Neutrophil Infiltration ◽  
Type I Interferons ◽  
Type I ◽  
Functional Variation ◽  
Chikv Infection ◽  
Blocking Antibody ◽  
Type I Ifns

ABSTRACT Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-β (IFN-β knockout [IFN-β-KO] mice or mice treated with an IFN-β-blocking antibody) or IFN-α (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice treated with a pan-IFN-α-blocking antibody). Mice lacking either IFN-α or IFN-β developed severe clinical disease following infection with CHIKV, with a marked increase in foot swelling compared to wild-type mice. Virological analysis revealed that mice lacking IFN-α sustained elevated infection in the infected ankle and in distant tissues. In contrast, IFN-β-KO mice displayed minimal differences in viral burdens within the ankle or at distal sites and instead had an altered cellular immune response. Mice lacking IFN-β had increased neutrophil infiltration into musculoskeletal tissues, and depletion of neutrophils in IFN-β-KO but not IRF7-KO mice mitigated musculoskeletal disease caused by CHIKV. Our findings suggest disparate roles for the IFN subtypes during CHIKV infection, with IFN-α limiting early viral replication and dissemination and IFN-β modulating neutrophil-mediated inflammation. IMPORTANCE Type I interferons (IFNs) possess a range of biological activity and protect against a number of viruses, including alphaviruses. Despite signaling through a shared receptor, there are established biochemical and functional differences among the IFN subtypes. The significance of our research is in demonstrating that IFN-α and IFN-β both have protective roles during acute chikungunya virus (CHIKV) infection but do so by distinct mechanisms. IFN-α limits CHIKV replication and dissemination, whereas IFN-β protects from CHIKV pathogenesis by limiting inflammation mediated by neutrophils. Our findings support the premise that the IFN subtypes have distinct biological activities in the antiviral response.

scholarly journals The class A macrophage scavenger receptor type I (SR-AI) recognizes complement iC3b and mediates NF-κB activation

2010 ◽  
Vol 1 (2) ◽  
pp. 174-187 ◽  
Author(s):  
Jason W. K. Goh ◽  
Yen Seah Tan ◽  
Alister W. Dodds ◽  
Kenneth B. M. Reid ◽  
Jinhua Lu
Keyword(s):  
Scavenger Receptor ◽  
Receptor Type ◽  
Type I ◽  
Class A ◽  
Macrophage Scavenger Receptor

scholarly journals Cell-intrinsic Innate Immune Responses against Chikungunya Virus in a Human Ex Vivo Synovial Fibroblast Model

2020 ◽  
Author(s):  
Fabian Pott ◽  
Richard J. P. Brown ◽  
Elena Neumann ◽  
Thomas Pietschmann ◽  
Christine Goffinet
Keyword(s):  
Chikungunya Virus ◽  
Cell Model ◽  
Ex Vivo ◽  
Antiviral Treatment ◽  
Treatment Strategies ◽  
Synovial Fibroblasts ◽  
International Travel ◽  
Type I ◽  
Insect Vector ◽  
Chikv Infection

AbstractIn recent years, newly and re-emerging arboviruses including Chikungunya virus (CHIKV), have caused growing concern due to expansion of insect vector ranges, mediated by the exponential increase in international travel and accelerating climate change. Due to the absence of specific antiviral treatment strategies and a protective vaccine, over 2 million CHIKV cases have been reported since 2005. Long-term morbidity after CHIKV infection includes debilitating chronic joint pain, which has associated health, social, individual, and economic impact. Here, we analyzed the early cell-intrinsic response to CHIKV infection in primary human synovial fibroblasts. This cell type represents a potential source of polyarthralgia induced by CHIKV infection. Synovial fibroblasts from healthy donors and osteoarthritic patients were similarly permissive to CHIKV infection. We observed a CHIKV infection-induced transcriptional profile that consisted in upregulation of several hundred interferon-stimulated genes, in addition to transcription factor-encoding genes and effector genes of proinflammatory pathways. In contrast, IL-6, which mediates chronic synovitis by stimulating neutrophil and macrophage infiltration into the joints, was barely secreted by CHIKV-infected fibroblasts. Finally, the cell-intrinsic response to interferon type I and III treatment of synovial fibroblasts differed from that of immortalized model cell lines. In synovial fibroblasts, CHIKV replication was impaired by IFN-α administered post-infection. In summary, primary human synovial fibroblasts serve as bona-fide ex vivo primary cell model of CHIKV infection and provide a valuable platform for studies of joint tissue-associated aspects of CHIKV immunopathogenesis.

Type I macrophage scavenger receptor contains α-helical and collagen-like coiled coils

Nature ◽  
1990 ◽  
Vol 343 (6258) ◽  
pp. 531-535 ◽  
Author(s):  
Tatsuhiko Kodama ◽  
Mason Freeman ◽  
Lucia Rohrer ◽  
James Zabrecky ◽  
Paul Matsudaira ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Coiled Coils ◽  
Type I ◽  
Macrophage Scavenger Receptor
Sign in / Sign up

Export Citation Format

Share Document