A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection?
Abstract
:1. Introduction
2. Methods
2.1. Study Population
2.2. Viruses
2.3. ERAP2 Genotyping Analyses
2.4. Isolation of PBMCs and Monocyte-Derived Macrophages (MDMs) Differentiation
2.5. Cell Cultures for Microbial Antigen Stimulation
2.6. In Vitro Infection of PBMCs and Calu3 Cells with SARS-CoV-2
2.7. In Vitro HIV-Infection Assay
2.8. Gene Expression Analysis
2.9. Quantigene Plex Gene Expression Assay
2.10. Western Blot Analyses
2.11. Statistical Analyses
3. Results
3.1. ERAP2 Allelic Variants Analyses
3.2. mRNA Expression of ERAPs in PBMCs from Subjects Carrying Different ERAP2 Genotypes Following Microbial Stimulation
3.3. Gene Expression of Immune Selected Effectors in PBMCs Following Microbial Stimulation
3.4. mRNA Expression of ERAPs in In Vitro SARS-CoV-2 Infected Calu3 Cell Lines and HIV-Infected PBMCs
3.5. ERAP2/Iso3 Protein Production by MDMs from HeteroAB Subjects Following Microbial Specific Stimulation
4. Discussion
Author Contributions
Funding
Conflicts of Interest
References
- Neefjes, J.; Jongsma, M.L.M.; Paul, P.; Bakke, O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat. Rev. Immunol. 2011, 11, 823–836. [Google Scholar] [CrossRef] [PubMed]
- Cifaldi, L.; Romania, P.; Lorenzi, S.; Locatelli, F.; Fruci, D. Role of Endoplasmic Reticulum Aminopeptidases in Health and Disease: From Infection to Cancer. Int. J. Mol. Sci. 2012, 13, 8338–8352. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Compagnone, M.; Fruci, D. Peptide Trimming for MHC Class I Presentation by Endoplasmic Reticulum Aminopeptidases. Methods Mol. Biol. Clifton NJ 2019, 1988, 45–57. [Google Scholar] [CrossRef]
- Saveanu, L.; Carroll, O.; Lindo, V.; Del Val, M.; Lopez, D.; Lepelletier, Y.; Greer, F.; Schomburg, L.; Fruci, D.; Niedermann, G.; et al. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat. Immunol. 2005, 6, 689–697. [Google Scholar] [CrossRef]
- Evnouchidou, I.; van Endert, P. Peptide trimming by endoplasmic reticulum aminopeptidases: Role of MHC class I binding and ERAP dimerization. Hum. Immunol. 2019, 80, 290–295. [Google Scholar] [CrossRef]
- Yao, Y.; Liu, N.; Zhou, Z.; Shi, L. Influence of ERAP1 and ERAP2 gene polymorphisms on disease susceptibility in different populations. Hum. Immunol. 2019, 80, 325–334. [Google Scholar] [CrossRef]
- Stamogiannos, A.; Koumantou, D.; Papakyriakou, A.; Stratikos, E. Effects of polymorphic variation on the mechanism of Endoplasmic Reticulum Aminopeptidase 1. Mol. Immunol. 2015, 67, 426–435. [Google Scholar] [CrossRef]
- López de Castro, J.A. How ERAP1 and ERAP2 Shape the Peptidomes of Disease-Associated MHC-I Proteins. Front. Immunol. 2018, 9. [Google Scholar] [CrossRef]
- Cagliani, R.; Riva, S.; Biasin, M.; Fumagalli, M.; Pozzoli, U.; Lo Caputo, S.; Mazzotta, F.; Piacentini, L.; Bresolin, N.; Clerici, M.; et al. Genetic diversity at endoplasmic reticulum aminopeptidases is maintained by balancing selection and is associated with natural resistance to HIV-1 infection. Hum. Mol. Genet. 2010, 19, 4705–4714. [Google Scholar] [CrossRef] [Green Version]
- Andrés, A.M.; Dennis, M.Y.; Kretzschmar, W.W.; Cannons, J.L.; Lee-Lin, S.-Q.; Hurle, B.; Schwartzberg, P.L.; Williamson, S.H.; Bustamante, C.D.; Nielsen, R.; et al. Balancing Selection Maintains a Form of ERAP2 that Undergoes Nonsense-Mediated Decay and Affects Antigen Presentation. PLoS Genet. 2010, 6. [Google Scholar] [CrossRef] [Green Version]
- Jostins, L.; Ripke, S.; Weersma, R.K.; Duerr, R.H.; McGovern, D.P.; Hui, K.Y.; Lee, J.C.; Philip Schumm, L.; Sharma, Y.; Anderson, C.A.; et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012, 491, 119–124. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kuiper, J.J.W.; Van Setten, J.; Ripke, S.; Van ‘T Slot, R.; Mulder, F.; Missotten, T.; Baarsma, G.S.; Francioli, L.C.; Pulit, S.L.; De Kovel, C.G.F.; et al. A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy. Hum. Mol. Genet. 2014, 23, 6081–6087. [Google Scholar] [CrossRef] [PubMed]
- Wiśniewski, A.; Kasprzyk, S.; Majorczyk, E.; Nowak, I.; Wilczyńska, K.; Chlebicki, A.; Zoń-Giebel, A.; Kuśnierczyk, P. ERAP1-ERAP2 haplotypes are associated with ankylosing spondylitis in Polish patients. Hum. Immunol. 2019, 80, 339–343. [Google Scholar] [CrossRef] [PubMed]
- Robinson, P.C.; Costello, M.E.; Leo, P.; Bradbury, L.A.; Hollis, K.; Cortes, A.; Lee, S.; Joo, K.B.; Shim, S.-C.; Weisman, M.; et al. ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients. Ann. Rheum. Dis. 2015, 74, 1627–1629. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chiaroni-Clarke, R.C.; Munro, J.E.; Chavez, R.A.; Pezic, A.; Allen, R.C.; Akikusa, J.D.; Piper, S.E.; Saffery, R.; Ponsonby, A.-L.; Ellis, J.A. Independent confirmation of juvenile idiopathic arthritis genetic risk loci previously identified by immunochip array analysis. Pediatr. Rheumatol. 2014, 12, 53. [Google Scholar] [CrossRef] [Green Version]
- Biasin, M.; Sironi, M.; Saulle, I.; de Luca, M.; la Rosa, F.; Cagliani, R.; Forni, D.; Agliardi, C.; lo Caputo, S.; Mazzotta, F.; et al. Endoplasmic reticulum aminopeptidase 2 haplotypes play a role in modulating susceptibility to HIV infection. AIDS Lond. Engl. 2013, 27, 1697–1706. [Google Scholar] [CrossRef] [Green Version]
- Saulle, I.; Ibba, S.V.; Torretta, E.; Vittori, C.; Fenizia, C.; Piancone, F.; Minisci, D.; Lori, E.M.; Trabattoni, D.; Gelfi, C.; et al. Endoplasmic Reticulum Associated Aminopeptidase 2 (ERAP2) Is Released in the Secretome of Activated MDMs and Reduces in vitro HIV-1 Infection. Front. Immunol. 2019, 10. [Google Scholar] [CrossRef] [Green Version]
- Evnouchidou, I.; Birtley, J.; Seregin, S.; Papakyriakou, A.; Zervoudi, E.; Samiotaki, M.; Panayotou, G.; Giastas, P.; Petrakis, O.; Georgiadis, D.; et al. A Common Single Nucleotide Polymorphism in Endoplasmic Reticulum Aminopeptidase 2 Induces a Specificity Switch That Leads to Altered Antigen Processing. J. Immunol. 2012. [Google Scholar] [CrossRef]
- Ye, C.J.; Chen, J.; Villani, A.-C.; Gate, R.E.; Subramaniam, M.; Bhangale, T.; Lee, M.N.; Raj, T.; Raychowdhury, R.; Li, W.; et al. Genetic analysis of isoform usage in the human anti-viral response reveals influenza-specific regulation of ERAP2 transcripts under balancing selection. Genome Res. 2018, 28, 1812–1825. [Google Scholar] [CrossRef] [Green Version]
- Saveanu, L.; Carroll, O.; Hassainya, Y.; Endert, P.V. Complexity, contradictions, and conundrums: Studying post-proteasomal proteolysis in HLA class I antigen presentation. Immunol. Rev. 2005, 207, 42–59. [Google Scholar] [CrossRef]
- Rossio, J.L.; Esser, M.T.; Suryanarayana, K.; Schneider, D.K.; Bess, J.W.; Vasquez, G.M.; Wiltrout, T.A.; Chertova, E.; Grimes, M.K.; Sattentau, Q.; et al. Inactivation of Human Immunodeficiency Virus Type 1 Infectivity with Preservation of Conformational and Functional Integrity of Virion Surface Proteins. J. Virol. 1998, 72, 7992–8001. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hui, K.P.Y.; Cheung, M.-C.; Perera, R.A.P.M.; Ng, K.-C.; Bui, C.H.T.; Ho, J.C.W.; Ng, M.M.T.; Kuok, D.I.T.; Shih, K.C.; Tsao, S.-W.; et al. Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: An analysis in ex-vivo and in-vitro cultures. Lancet Respir. Med. 2020, 8, 687–695. [Google Scholar] [CrossRef]
- Batéjat, C.; Grassin, Q.; Manuguerra, J.-C.; Leclercq, I. Heat inactivation of the Severe Acute Respiratory Syndrome Coronavirus 2. bioRxiv 2020. [Google Scholar] [CrossRef]
- Merlini, E.; Tincati, C.; Biasin, M.; Saulle, I.; Cazzaniga, F.A.; d’Arminio Monforte, A.; Cappione, A.J.I.; Snyder-Cappione, J.; Clerici, M.; Marchetti, G.C. Stimulation of PBMC and Monocyte-Derived Macrophages via Toll-Like Receptor Activates Innate Immune Pathways in HIV-Infected Patients on Virally Suppressive Combination Antiretroviral Therapy. Front. Immunol. 2016, 7. [Google Scholar] [CrossRef] [PubMed]
- Saulle, I.; Ibba, S.V.; Vittori, C.; Fenizia, C.; Mercurio, V.; Vichi, F.; Caputo, S.L.; Trabattoni, D.; Clerici, M.; Biasin, M. Sterol metabolism modulates susceptibility to HIV-1 Infection. AIDS Lond. Engl. 2020. [Google Scholar] [CrossRef]
- Wu, T.G.; Rose, W.A.; Albrecht, T.B.; Knutson, E.P.; König, R.; Perdigão, J.R.; Nguyen, A.P.A.; Fleischmann, W.R. IFN-alpha-induced murine B16 melanoma cancer vaccine cells: Induction and accumulation of cell-associated IL-15. J. Interf. Cytokine Res. Off. J. Int. Soc. Interf. Cytokine Res. 2007, 27, 13–22. [Google Scholar] [CrossRef]
- Nordmark, G.; Ronnblom, M.-L.E.; Primary, L. Sjogren’s Syndrome and the Type I Interferon System. Available online: https://www.eurekaselect.com/101237/article (accessed on 15 August 2020).
- Kirou, K.A.; Gkrouzman, E. Anti-interferon alpha treatment in SLE. Clin. Immunol. 2013, 148, 303–312. [Google Scholar] [CrossRef]
- Raschi, E.; Chighizola, C.B.; Cesana, L.; Privitera, D.; Ingegnoli, F.; Mastaglio, C.; Meroni, P.L.; Borghi, M.O. Immune complexes containing scleroderma-specific autoantibodies induce a profibrotic and proinflammatory phenotype in skin fibroblasts. Arthritis Res. Ther. 2018, 20, 187. [Google Scholar] [CrossRef] [Green Version]
- Lappalainen, T.; Sammeth, M.; Friedländer, M.R.; Ac‘t Hoen, P.; Monlong, J.; Rivas, M.A.; Gonzàlez-Porta, M.; Kurbatova, N.; Griebel, T.; Ferreira, P.G.; et al. Transcriptome and genome sequencing uncovers functional variation in humans. Nature 2013, 501, 506–511. [Google Scholar] [CrossRef]
- The Crystal Structure of Human Endoplasmic Reticulum Aminopeptidase 2 Reveals the Atomic Basis for Distinct Roles in Antigen Processing | Biochemistry. Available online: https://pubs.acs.org/doi/10.1021/bi201230p (accessed on 17 August 2020).
- de Castro, J.A.L.; Stratikos, E. Intracellular antigen processing by ERAP2: Molecular mechanism and roles in health and disease. Hum. Immunol. 2019, 80, 310–317. [Google Scholar] [CrossRef]
- Evnouchidou, I.; Weimershaus, M.; Saveanu, L.; Endert, P. van ERAP1–ERAP2 Dimerization Increases Peptide-Trimming Efficiency. J. Immunol. 2014. [Google Scholar] [CrossRef] [PubMed]
- Saulle, I.; Vicentini, C.; Clerici, M.; Biasin, M. An Overview on ERAP Roles in Infectious Diseases. Cells 2020, 9, 720. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Forni, D.; Cagliani, R.; Tresoldi, C.; Pozzoli, U.; Gioia, L.D.; Filippi, G.; Riva, S.; Menozzi, G.; Colleoni, M.; Biasin, M.; et al. An Evolutionary Analysis of Antigen Processing and Presentation across Different Timescales Reveals Pervasive Selection. PLoS Genet. 2014, 10, e1004189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lori, E.M.; Cozzi-Lepri, A.; Tavelli, A.; Mercurio, V.; Ibba, S.V.; Lo Caputo, S.; Castelli, F.; Castagna, A.; Gori, A.; Marchetti, G.; et al. Evaluation of the effect of protective genetic variants on cART success in HIV-1-infected patients. J. Biol. Regul. Homeost. Agents 2020, 34. [Google Scholar] [CrossRef]
- Genetic Risk Factors for Death with SARS-CoV-2 from the UK Biobank | medRxiv. Available online: https://www.medrxiv.org/content/10.1101/2020.07.01.20144592v1 (accessed on 15 August 2020).
- Stamatakis, G.; Samiotaki, M.; Mpakali, A.; Panayotou, G.; Stratikos, E. Generation of SARS-CoV-2 S1 spike glycoprotein putative antigenic epitopes in vitro by intracellular aminopeptidases. bioRxiv 2020. [Google Scholar] [CrossRef]
- Hisatsune, C.; Ebisui, E.; Usui, M.; Ogawa, N.; Suzuki, A.; Mataga, N.; Takahashi-Iwanaga, H.; Mikoshiba, K. ERp44 Exerts Redox-Dependent Control of Blood Pressure at the ER. Mol. Cell 2015, 58, 1015–1027. [Google Scholar] [CrossRef] [Green Version]
- Cui, X.; Rouhani, F.N.; Hawari, F.; Levine, S.J. An Aminopeptidase, ARTS-1, Is Required for Interleukin-6 Receptor Shedding. J. Biol. Chem. 2003, 278, 28677–28685. [Google Scholar] [CrossRef] [Green Version]
- Michot, J.-M.; Albiges, L.; Chaput, N.; Saada, V.; Pommeret, F.; Griscelli, F.; Balleyguier, C.; Besse, B.; Marabelle, A.; Netzer, F.; et al. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: A case report. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2020, 31, 961–964. [Google Scholar] [CrossRef]
- Ranjit, S.; Wong, J.Y.; Tan, J.W.; Sin Tay, C.; Lee, J.M.; Yin Han Wong, K.; Pojoga, L.H.; Brooks, D.L.; Garza, A.E.; Maris, S.A.; et al. Sex-specific differences in endoplasmic reticulum aminopeptidase 1 modulation influence blood pressure and renin-angiotensin system responses. JCI Insight 2019, 4. [Google Scholar] [CrossRef] [Green Version]
- Golovko, L.; Lyons, L.A.; Liu, H.; Sørensen, A.; Wehnert, S.; Pedersen, N.C. Genetic susceptibility to feline infectious peritonitis in Birman cats. Virus Res. 2013, 175, 58–63. [Google Scholar] [CrossRef]
- Cong, F.; Liu, X.; Han, Z.; Shao, Y.; Kong, X.; Liu, S. Transcriptome analysis of chicken kidney tissues following coronavirus avian infectious bronchitis virus infection. BMC Genom. 2013, 14, 743. [Google Scholar] [CrossRef] [PubMed] [Green Version]
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Saulle, I.; Vanetti, C.; Goglia, S.; Vicentini, C.; Tombetti, E.; Garziano, M.; Clerici, M.; Biasin, M. A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? Cells 2020, 9, 1951. https://doi.org/10.3390/cells9091951
Saulle I, Vanetti C, Goglia S, Vicentini C, Tombetti E, Garziano M, Clerici M, Biasin M. A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? Cells. 2020; 9(9):1951. https://doi.org/10.3390/cells9091951
Chicago/Turabian StyleSaulle, Irma, Claudia Vanetti, Sara Goglia, Chiara Vicentini, Enrico Tombetti, Micaela Garziano, Mario Clerici, and Mara Biasin. 2020. "A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection?" Cells 9, no. 9: 1951. https://doi.org/10.3390/cells9091951