Feline Infectious Peritonitis Virus Nsp5 Inhibits Type I Interferon Production by Cleaving NEMO at Multiple Sites

Chen, Si; Jin, Tian; Li, Zhijie; Kang, Huifang; Zhang, Jikai; Huang, Jiapei; Yin, Hong; Hu, Xiaoliang; Qu, Liandong

doi:10.3390/v12010043

Cited by 51 publications

(62 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…COVID-19 NSP5 is also highly homologous to SARS NSP5 (96% identity, 98% similarity). Its homologous proteins in a variety of coronaviruses have been proven to impair IFN response 31 – 33 . Our study provide experimental evidence to show the existence of NSP5-specific antibodies in convalescents.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses

et al. 2020

View full text Add to dashboard Cite

We still know very little about how the human immune system responds to SARS-CoV-2. Here we construct a SARS-CoV-2 proteome microarray containing 18 out of the 28 predicted proteins and apply it to the characterization of the IgG and IgM antibodies responses in the sera from 29 convalescent patients. We find that all these patients had IgG and IgM antibodies that specifically bind SARS-CoV-2 proteins, particularly the N protein and S1 protein. Besides these proteins, significant antibody responses to ORF9b and NSP5 are also identified. We show that the S1 specific IgG signal positively correlates with age and the level of lactate dehydrogenase (LDH) and negatively correlates with lymphocyte percentage. Overall, this study presents a systemic view of the SARS-CoV-2 specific IgG and IgM responses and provides insights to aid the development of effective diagnostic, therapeutic and vaccination strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses

et al. 2020

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Global profiling of SARS-CoV-2 specific IgG/ IgM responses of convalescents using a proteome microarray

Jiang

Yang

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

COVID-19 is caused by SARS-CoV-2, and has become a global pandemic. There is no highly effective medicine or vaccine, most of the patients were recovered by their own immune response, especially the virus specific IgG and IgM responses. However, the IgG/ IgM responses is barely known. To enable the global understanding of SARS-CoV-2 specific IgG/ IgM responses, a SARS-CoV-2 proteome microarray with 18 out of the 28 predicted proteins was constructed. The microarray was applied to profile the IgG/ IgM responses with 29 convalescent sera. The results suggest that at the convalescent phase 100% of patients had IgG/ IgM responses to SARS-CoV-2, especially to protein N, S1 but not S2. S1 purified from mammalian cell demonstrated the highest performance to differentiate COVID-19 patients from controls. Besides protein N and S1, significant antibody responses to ORF9b and NSP5 were also identified. Indepth analysis showed that the level of S1 IgG positively correlate to age and the level of LDH (lactate dehydrogenase), especially for women, while the level of S1 IgG negatively correlate to Ly% (Lymphocyte percentage). This study presents the first whole picture of the SARS-CoV-2 specific IgG/ IgM responses, and provides insights to develop precise immuno-diagnostics, effective treatment and vaccine. Highlights• A SARS-CoV-2 proteome microarray contains 18 of the 28 predicted proteins• The 1 st global picture of the SARS-CoV-2 specific IgG/ IgM response reveals that at the convalescent phase, 100% of patients have IgG/ IgM responses to protein N and S1• Significant antibody responses against ORF9b and NSP5 were identified • Protein S1 specific IgG positively correlates to age and LDH, while negatively to Ly%

show abstract

“…SARS-CoV PLpro has also been reported to also activate TGF-β1 signalling [23] or down-regulate p53 [24]. Similarly, 3CLpro from the feline coronavirus, feline infectious peritonitis virus (FIPV), inhibits type I interferon signalling through cleavage of NEMO [25], while the porcine deltacoronavirus (PDCoV) 3CLpro cleaves STAT2. SARS-CoV 3CLpro is responsible for virus-induced apoptosis [26].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 proteases cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species and the search for reservoir hosts

Moustaqil

Ollivier

Chiu

et al. 2020

Preprint

View full text Add to dashboard Cite

The genome of SARS-CoV-2 (SARS2) encodes for two viral proteases (NSP3/ papain-like protease and NSP5/ 3C-like protease or major protease) that are responsible for cleaving viral polyproteins for successful replication. NSP3 and NSP5 of SARS-CoV (SARS1) are known interferon antagonists. Here, we examined whether the protease function of SARS2 NSP3 and NSP5 target proteins involved in the host innate immune response. We designed a fluorescent based cleavage assay to rapidly screen the protease activity of NSP3 and NSP5 on a library of 71 human innate immune proteins (HIIPs), covering most pathways involved in human innate immunity. By expressing each of these HIIPs with a genetically encoded fluorophore in a cell-free system and titrating in the recombinant protease domain of NSP3 or NSP5, we could readily detect cleavage of cognate HIIPs on SDS-page gels. We identified 3 proteins that were specifically and selectively cleaved by NSP3 or NSP5: IRF-3, and NLRP12 and TAB1, respectively. Direct cleavage of IRF3 by NSP3 could explain the blunted Type-I IFN response seen during SARS-CoV-2 infections while NSP5 mediated cleavage of NLRP12 and TAB1 point to a molecular mechanism for enhanced production of IL-6 and inflammatory response observed in COVID-19 patients. Surprisingly, both NLRP12 and TAB1 have each two distinct cleavage sites. We demonstrate that in mice, the second cleavage site of NLRP12 is absent. We pushed this comparative alignment of IRF-3 and NLRP12 homologs and show that the lack or presence of cognate cleavage motifs in IRF-3 and NLRP12 could contribute to the presentation of disease in cats and tigers, for example. Our findings provide an explanatory framework for in-depth studies into the pathophysiology of COVID-19 and should facilitate the search or development of more effective animal models for severe COVID-19. Finally, we discovered that one particular species of bats, David's Myotis, possesses the five cleavage sites found in humans for NLRP12, TAB1 and IRF3. These bats are endemic from the Hubei province in China and we discuss its potential role as reservoir for the evolution of SARS1 and SASR2.

show abstract

Feline Infectious Peritonitis Virus Nsp5 Inhibits Type I Interferon Production by Cleaving NEMO at Multiple Sites

Cited by 51 publications

References 54 publications

SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses

SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses

Global profiling of SARS-CoV-2 specific IgG/ IgM responses of convalescents using a proteome microarray

SARS-CoV-2 proteases cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species and the search for reservoir hosts

Contact Info

Product

Resources

About