Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis

mBio - Tập 9 Số 5 - 2018
Lisa E. Gralinski1, Timothy P. Sheahan1, Thomas E. Morrison2, Vineet D. Menachery1,3, Kara Jensen1, Sarah R. Leist1, Alan C. Whitmore4, Mark T. Heise4, Ralph S. Baric1
1Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
2Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
3Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, Texas USA
4Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA

Tóm tắt

The complement system is a critical part of host defense to many bacterial, viral, and fungal infections. It works alongside pattern recognition receptors to stimulate host defense systems in advance of activation of the adaptive immune response. In this study, we directly test the role of complement in SARS-CoV pathogenesis using a mouse model and show that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged. Complement-deficient mice have reduced neutrophilia in their lungs and reduced systemic inflammation, consistent with the observation that SARS-CoV pathogenesis is an immune-driven disease. These data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.

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Tài liệu tham khảo

10.1126/science.1092002

10.1126/science.1085952

10.1086/420743

10.1056/NEJMoa1211721

10.1097/MCP.0000000000000046

10.1038/nm.3985

10.1038/nature12711

10.1128/CMR.00023-07

10.1086/429631

10.1111/j.1399-0039.2005.00476.x

10.1128/JVI.00554-10

10.1016/j.imbio.2006.12.001

10.1186/1471-2334-9-51

10.2215/CJN.06230614

10.1038/ni.1923

10.1038/s41426-018-0063-8

10.1016/j.virol.2010.12.045

10.1080/08916930600739456

10.1186/1471-2172-11-64

10.1078/0171-2985-00155

10.4049/jimmunol.1101789

10.1371/journal.pone.0017377

10.1128/mBio.00271-13

10.1371/journal.pone.0131451

10.1056/NEJMoa030685

10.1016/j.chom.2016.01.007

10.1016/j.jcpa.2014.01.004

10.1128/JVI.01049-10

10.1556/EuJMI.2.2012.2.2

10.3389/fimmu.2015.00262

10.1111/1574-6976.12080

10.1016/j.chom.2010.07.007

10.1084/jem.20052388

10.1165/rcmb.2012-0428OC

10.1007/978-1-4614-0106-3_9

10.1038/emi.2015.28

10.1016/j.virol.2008.03.022

10.1128/mBio.00276-11

Ikeda F, Haraguchi Y, Jinno A, Iino Y, Morishita Y, Shiraki H, Hoshino H. 1998. Human complement component C1q inhibits the infectivity of cell-free HTLV-I. J Immunol 161:5712–5719.

10.1128/JVI.02799-06

10.1371/journal.ppat.1002586

10.1016/j.jaut.2009.11.014

10.1086/491479

10.1093/intimm/dxr007

10.3201/eid0909.030362

10.1099/vir.0.061986-0

10.1038/nri3843

10.1073/pnas.76.10.5299

10.1146/annurev.immunol.23.021704.115835

10.2174/187152809788681038

10.1128/JVI.06053-11

10.1128/CMR.00048-09

10.1534/g3.117.041434

10.1128/mBio.00638-15

10.1126/science.282.5396.2085

Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S. 1999. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the lps gene product. J Immunol 162:3749–3752.

10.1371/journal.pgen.1005504

10.1128/JVI.00087-13

10.1016/S0046-8177(03)00367-8

10.1016/j.cell.2012.03.047

10.1016/j.neurobiolaging.2005.08.008

10.1016/S0140-6736(80)91403-8

10.1172/JCI109866

10.1126/scitranslmed.aal3653

10.1371/journal.ppat.0030005

10.1073/pnas.1735582100

10.1128/JVI.02041-07

10.1165/rcmb.2013-0086MA

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