T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice
Open accessAbstract
A dysregulated innate immune response and exuberant cytokine/chemokine expression are believed to be critical factors in the pathogenesis of severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV). However, we recently showed that inefficient immune activation and a poor virus-specific T cell response underlie severe disease in SARS-CoV-infected mice. Here, we extend these results to show that virus-specific T cells, in the absence of activation of the innate immune response, were sufficient to significantly enhance survival and diminish clinical disease. We demonstrated that T cells are responsible for virus clearance, as intravenous adoptive transfer of SARS-CoV-immune splenocytes or in vitro -generated T cells to SCID or BALB/c mice enhanced survival and reduced virus titers in the lung. Enhancement of the number of virus-specific CD8 T cells by immunization with SARS-CoV peptide-pulsed dendritic cells also resulted in a robust T cell response, earlier virus clearance, and increased survival. These studies are the first to show that T cells play a crucial role in SARS-CoV clearance and that a suboptimal T cell response contributes to the pathological changes observed in SARS. They also provide a new approach to SARS vaccine design.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Anti-S T-cell responses to SARS- and MERS-CoVs contribute toward viral clearance in normal as well as aged mice infected with SARS- or MERS-CoV, respectively.
“anti-S T-cell responses to the related SARS- and MERS-CoVs contribute toward viral clearance in normal as well as aged mice infected with SARS- or MERS-CoV, respectively (43–45).”
From An <i>Alphavirus</i> -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [43]
The Results identify S366 as an epitope of the SARS-CoV spike protein and report that transferring S366-specific CD8 T cells accelerated viral clearance in infected BALB/c mice. This supports the SARS-CoV portion of the claim, but the paper does not establish the claimed effect in aged mice or in MERS-CoV-infected mice. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873 · see citing works
Coronavirus as a possible cause of severe acute respiratory syndrome
Peiris, M. J. S., Lai, S., Poon, L. L. M., Guan, Y., Yam, L., Lim, W., Nicholls, J. M., Yee, W., Yan, W., Cheung, M., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13077-2 · Cited by 2,916 · see citing works
Bats Are Natural Reservoirs of SARS-Like Coronaviruses
Li, W., Shi, Z., Yu, M., Ren, W., Smith, C. S., Epstein, J. H., Wang, H., Crameri, G. S., Hú, Z., Zhang, H., et al. (2005) · Science · doi:10.1126/science.1118391 · Cited by 2,571 · see citing works
Peiris, J., Chu, C., Cheng, V., Chan, K., Hung, I., Poon, L., Law, K., Tang, B., Hon, T., Chan, C., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13412-5 · Cited by 2,375 · see citing works
SYFPEITHI: database for MHC ligands and peptide motifs
Rammensee, H., Bachmann, J., Emmerich, N., Bachor, O. A., & Stevanović, S. (1999) · Immunogenetics · doi:10.1007/s002510050595 · Cited by 2,316 · see citing works
van Rooijen, N., & Sanders, A. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90012-4 · Cited by 1,763 · see citing works
MHC ligands and peptide motifs: first listing
Rammensee, H., Friede, T., & Stevanović, S. (1995) · Immunogenetics · doi:10.1007/bf00172063 · Cited by 1,638 · see citing works
T-cell quality in memory and protection: implications for vaccine design
Seder, R. A., Darrah, P. A., & Roederer, M. (2008) · Nature reviews. Immunology · doi:10.1038/nri2274 · Cited by 1,541 · see citing works
A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice
Yang, Z.-Y., Kong, W., Huang, Y., Roberts, A., Murphy, B., Subbarao, K., & Nabel, G. (2004) · Nature · doi:10.1038/nature02463 · Cited by 688 · see citing works
Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10
Sun, J., Madan, R., Karp, C. L., & Braciale, T. J. (2009) · Nature Medicine · doi:10.1038/nm.1929 · Cited by 616 · see citing works
Wong, R., Wu, A., To, K.-F., Lee, N., Lam, C., Wong, C., Chan, P. K., Ng, M., Yu, L., Hui, D., et al. (2003) · British medical journal · doi:10.1136/bmj.326.7403.1358 · Cited by 566 · see citing works
CD8+ T cells clear influenza virus by perforin or Fas-dependent processes
Topham, D. J., Tripp, R. A., & Doherty, P. C. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.11.5197 · Cited by 486 · see citing works
A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice
Roberts, A., Deming, D., Paddock, C. D., Cheng, A., Yount, B. L., Vogel, L., Herman, B. D., Sheahan, T., Heise, M. T., Genrich, G. L., et al. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030005 · Cited by 447 · see citing works
Cutting Edge: Rapid In Vivo Killing by Memory CD8 T Cells
Barber, D. L., Wherry, E. J., & Ahmed, R. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.1.27 · Cited by 444 · see citing works
Thepen, T., van Rooijen, N., & Kraal, G. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.170.2.499 · Cited by 421 · see citing works
Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination
Badovinac, V. P., Messingham, K. N., Jabbari, A., Haring, J. S., & Harty, J. T. (2005) · Nature Medicine · doi:10.1038/nm1257 · Cited by 403 · see citing works
Chen, J., Lau, Y. F., Lamirande, E. W., Paddock, C. D., Bartlett, J. H., Zaki, S. R., & Subbarao, K. (2009) · Journal of Virology · doi:10.1128/jvi.01281-09 · Cited by 400 · see citing works
Cameron, M. J., Ran, L., Xu, L., Danesh, A., Bermejo-Martin, J. F., Cameron, C. M., Muller, M. P., Gold, W. L., Richardson, S. E., Poutanen, S. M., et al. (2007) · Journal of Virology · doi:10.1128/jvi.00527-07 · Cited by 386 · see citing works
Reche, P. A., Glutting, J.-P., Zhang, H., & Reinherz, E. L. (2004) · Immunogenetics · doi:10.1007/s00251-004-0709-7 · Cited by 384 · see citing works
Legge, K. L., & Braciale, T. J. (2003) · Immunity · doi:10.1016/s1074-7613(03)00023-2 · Cited by 353 · see citing works
Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates
Smits, S. L., de Lang, A., van den Brand, J. M. A., Leijten, L. M. E., van IJcken, W. F. J., Eijkemans, M. J. C., van Amerongen, G., Kuiken, T., Andeweg, A. C., Osterhaus, A. D. M. E., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000756 · Cited by 331 · see citing works
Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells.
Hou, S., Doherty, P. C., Zijlstra, M., Jaenisch, R., & Katz, J. M. (1992) · Journal of Immunology · doi:10.4049/jimmunol.149.4.1319 · Cited by 271 · see citing works
MyD88 Is Required for Protection from Lethal Infection with a Mouse-Adapted SARS-CoV
Sheahan, T. P., Morrison, T. E., Funkhouser, W., Uematsu, S., Akira, S., Baric, R. S., & Heise, M. T. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000240 · Cited by 207 · see citing works
Williamson, J. S., & Stohlman, S. A. (1990) · Journal of Virology · doi:10.1128/jvi.64.9.4589-4592.1990 · Cited by 185 · see citing works
Rockx, B., Baas, T., Zornetzer, G. A., Haagmans, B. L., Sheahan, T. P., Frieman, M. B., Dyer, M. D., Teal, T. H., Proll, S. C., van den Brand, J. M. A., et al. (2009) · Journal of Virology · doi:10.1128/jvi.00127-09 · Cited by 175 · see citing works
Xia, W., Carvalho-Pinto, C. E., & Kradin, R. L. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.4.1275 · Cited by 163 · see citing works
Zhao, J., Zhao, J., van Rooijen, N., & Perlman, S. M. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000636 · Cited by 151 · see citing works
Self-citationNagata, N., Iwata, N., Hasegawa, H., Fukushi, S., Harashima, A., Sato, Y., Saijo, M., Taguchi, F., Morikawa, S., & Sata, T. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.071060 · Cited by 82 · see citing works
Zhi, Y., Kobinger, G., Jordan, H. M., Suchma, K., Weiss, S. R., Shen, H., Schumer, G., Gao, G., Boyer, J. L., Crystal, R. G., et al. (2005) · Virology · doi:10.1016/j.virol.2005.01.050 · Cited by 82 · see citing works
Mapping T cell epitopes by flow cytometry
Hoffmeister, B. (2003) · Methods · doi:10.1016/s1046-2023(02)00349-3 · Cited by 74 · see citing works
Severe Acute Respiratory Syndrome–associated Coronavirus in Lung Tissue
Mazzulli, T., Farcas, G. A., Poutanen, S. M., Willey, B. M., Low, D. E., BUTANY, J. W., Asa, S. L., & Kain, K. C. (2004) · Emerging infectious diseases · doi:10.3201/eid1001.030404 · Cited by 65 · see citing works
HUANG, J., CAO, Y., Du, J., Bu, X., MA, R., & Wu, C. (2007) · Vaccine · doi:10.1016/j.vaccine.2007.06.047 · Cited by 63 · see citing works
Nagata, N., Iwata, N., Hasegawa, H., Fukushi, S., Yokoyama, M., Harashima, A., Sato, Y., Saijo, M., Morikawa, S., & Sata, T. (2006) · Journal of Virology · doi:10.1128/jvi.01967-06 · Cited by 62 · see citing works
Liu, L., Fang, Q., Dèng, F., Wang, H., Yi, C. E., Ba, L., Yu, W., Lin, R. D., Li, T., Hú, Z., et al. (2007) · Journal of Virology · doi:10.1128/jvi.02389-06 · Cited by 57 · see citing works
Baas, T., Roberts, A., Teal, T. H., Vogel, L., Chen, J., Tumpey, T. M., Katze, M. G., & Subbarao, K. (2008) · Journal of Virology · doi:10.1128/jvi.00489-08 · Cited by 52 · see citing works
Identification of synthetic vaccine candidates against SARS CoV infection
Lien, S., Shih, Y.-P., Chen, H., Tsai, J.-P., Leng, C., Lin, M.-H., Lin, L.-H., Liu, H., Chou, A., Chang, Y.-W., et al. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.04.164 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Wu, C., Chen, X., Cai, Y., Xia, J., Zhou, X., Xu, S., Huang, H., Zhang, L., Zhou, X., Du, C., et al. (2020) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2020.0994 · Cited by 8,249 · see citing works
The trinity of COVID-19: immunity, inflammation and intervention
Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., & Ng, L. F. P. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0311-8 · Cited by 4,360 · see citing works
Coronaviruses: An Overview of Their Replication and Pathogenesis
Fehr, A. R., & Perlman, S. M. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2438-7_1 · Cited by 3,784 · see citing works
Self-citationGrifoni, A., Weiskopf, D., Ramirez, S. I., Mateus, J., Dan, J. M., Moderbacher, C. R., Rawlings, S. A., Sutherland, A., Premkumar, L., Jadi, R. S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.015 · Cited by 3,595 · see citing works
Channappanavar, R., & Perlman, S. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0629-x · Cited by 2,524 · see citing works
Self-citationSingle-cell landscape of bronchoalveolar immune cells in patients with COVID-19
Liao, M., Liu, Y., Yuan, J., Wen, Y., Xu, G., Zhao, J., Cheng, L., Li, J., Wang, X., Wang, F., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0901-9 · Cited by 2,614 · see citing works
Self-citationZhu, F.-C., Li, Y.-H., Guan, X.-H., Hou, L.-H., Wang, W.-J., Li, J.-X., Wu, S.-P., Wang, B.-S., Wang, Z., Wang, L., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31208-3 · Cited by 1,382 · see citing works
Channappanavar, R., Fehr, A. R., Vijay, R., Mack, M., Zhao, J., Meyerholz, D. K., & Perlman, S. M. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.01.007 · Cited by 1,400 · see citing works
Self-citationFrom SARS to MERS, Thrusting Coronaviruses into the Spotlight
Song, Z., Xu, Y., Bao, L., Zhang, L., Yü, P., Qu, Y., Zhu, H., Zhao, W., Han, Y., & Qin, C. (2019) · Viruses · doi:10.3390/v11010059 · Cited by 1,268 · see citing works
The T cell immune response against SARS-CoV-2
Moss, P. A. H. (2022) · Nature Immunology · doi:10.1038/s41590-021-01122-w · Cited by 1,205 · see citing works
Viral targets for vaccines against COVID-19
Dai, L., & Gao, G. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00480-0 · Cited by 949 · see citing works
Immunological considerations for COVID-19 vaccine strategies
Jeyanathan, M., Afkhami, S., Smaill, F., Miller, M. S., Lichty, B. D., & Xing, Z. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-00434-6 · Cited by 1,015 · see citing works
Weiss, S. R., & Leibowitz, J. L. (2011) · Advances in virus research · doi:10.1016/b978-0-12-385885-6.00009-2 · Cited by 899 · see citing works
Liu, L., Wei, Q., Lin, Q., Fang, J., Wang, H., Kwok, H., Tang, H., Nishiura, K., Peng, J., Tan, Z., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.123158 · Cited by 830 · see citing works
Self-citationSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update
Pal, M. S., Berhanu, G., Desalegn, C., & Kandi, V. (2020) · Cureus · doi:10.7759/cureus.7423 · Cited by 831 · see citing works
A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity
Yang, H. J., Wang, W., Chen, Z., Lu, S., Yang, F., Bi, Z., Bao, L., Mo, F., Li, X., Huang, Y., et al. (2020) · Nature · doi:10.1038/s41586-020-2599-8 · Cited by 753 · see citing works
Liu, B., Li, M., Zhou, Z., Guan, X., & Xiang, Y. (2020) · Journal of Autoimmunity · doi:10.1016/j.jaut.2020.102452 · Cited by 763 · see citing works
A decade after SARS: strategies for controlling emerging coronaviruses
Graham, R. L., Donaldson, E., & Baric, R. S. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro3143 · Cited by 676 · see citing works
Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis
Gralinski, L. E., Sheahan, T. P., Morrison, T. E., Menachery, V. D., Jensen, K., Leist, S. R., Whitmore, A. C., Heise, M. T., & Baric, R. S. (2018) · mBio · doi:10.1128/mbio.01753-18 · Cited by 656 · see citing works
SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition
Nelde, A., Bilich, T., Heitmann, J. S., Maringer, Y., Salih, H. R., Roerden, M., Lübke, M., Bauer, J., Rieth, J., Wacker, M., et al. (2021) · Nature Immunology · doi:10.1038/s41590-020-00808-x · Cited by 582 · see citing works
Nikolich-Zugich, J., Knox, K. S., Rios, C. T., Natt, B., Bhattacharya, D., & Fain, M. J. (2020) · GeroScience · doi:10.1007/s11357-020-00186-0 · Cited by 577 · see citing works
IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes
Channappanavar, R., Fehr, A. R., Zheng, J. H., Wohlford-Lenane, C., Abrahante, J. E., Mack, M., Sompallae, R. R., McCray, P. B., Meyerholz, D. K., & Perlman, S. M. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126363 · Cited by 556 · see citing works
Self-citationA systematic review of SARS-CoV-2 vaccine candidates
Dong, Y., Dai, T., Wei, Y., Zhang, L., Zheng, M., & Zhou, F. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00352-y · Cited by 541 · see citing works
Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses
Zhou, R., To, K. K.-W., Wong, Y.-C., Liu, L., Zhou, B., Li, X., Huang, H., Mo, Y., Luk, T.-Y., Lau, T. T.-K., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.07.026 · Cited by 531 · see citing works
T cell-mediated immune response to respiratory coronaviruses
Channappanavar, R., Zhao, J., & Perlman, S. (2014) · Immunologic Research · doi:10.1007/s12026-014-8534-z · Cited by 512 · see citing works
Self-citationAirway Memory CD4+ T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses
Zhao, J., Zhao, J., Mangalam, A. K., Channappanavar, R., Fett, C., Meyerholz, D. K., Agnihothram, S., Baric, R. S., David, C. S., & Perlman, S. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.006 · Cited by 496 · see citing works
Self-citationSevere Acute Respiratory Syndrome
Hui, D. S. C., & Zumla, A. I. (2019) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2019.07.001 · Cited by 507 · see citing works
COVID-19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning
Ong, E., Wong, M. U., Huffman, A., & He, Y. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01581 · Cited by 499 · see citing works
Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent
Mazzoni, A., Salvati, L., Maggi, L., Capone, M., Vanni, A., Spinicci, M., Mencarini, J., Caporale, R., Peruzzi, B., Antonelli, A., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci138554 · Cited by 502 · see citing works
Newton, A. H., Cardani, A. N., & Braciale, T. J. (2016) · Seminars in Immunopathology · doi:10.1007/s00281-016-0558-0 · Cited by 479 · see citing works
Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past
Shah, V. K., Firmal, P., Alam, A., Ganguly, D., & Chattopadhyay, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01949 · Cited by 471 · see citing works
Chu, H., Zhou, J., Wong, B. H.-Y., Li, C., Chan, J. F.-W., Cheng, Z.-S., Yang, D., Wang, D., Lee, A. C.-Y., Li, C., et al. (2016) · Journal of Infectious Diseases · doi:10.1093/infdis/jiv380 · Cited by 448 · see citing works
Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment
Sun, J., Zhuang, Z., Zheng, J. H., Li, K., Wong, R. L.-Y., Liu, D., Huang, J., He, J., Zhu, A., Zhao, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.010 · Cited by 434 · see citing works
Self-citationMemory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection
Ng, O.-W., Chia, A., Tan, A. T., Jadi, R. S., Leong, H. N., Bertoletti, A., & Tan, Y.-J. (2016) · Vaccine · doi:10.1016/j.vaccine.2016.02.063 · Cited by 436 · see citing works
COVID-19 in Children, Pregnancy and Neonates: A Review of Epidemiologic and Clinical Features
Zimmermann, P., & Curtis, N. C. (2020) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0000000000002700 · Cited by 442 · see citing works
Channappanavar, R., Fett, C., Zhao, J., Meyerholz, D. K., & Perlman, S. (2014) · Journal of Virology · doi:10.1128/jvi.01505-14 · Cited by 411 · see citing works
Self-citationT-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV
Liu, W. J., Zhao, M. J., Liu, K., Xu, K., Wong, G., Tan, W., & Gao, G. F. (2016) · Antiviral Research · doi:10.1016/j.antiviral.2016.11.006 · Cited by 395 · see citing works
SARS-CoV-2, COVID-19 and the aging immune system
Bartleson, J. M., Radenkovic, D., Covarrubias, A. J., Furman, D., Winer, D. A., & Verdin, E. (2021) · Nature Aging · doi:10.1038/s43587-021-00114-7 · Cited by 359 · see citing works
MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19
Bilezikian, J. P., Bikle, D. D., Hewison, M., Lazaretti‐Castro, M., Formenti, A. M., Gupta, A., Madhavan, M. V., Nair, N., Babalyan, V., Hutchings, N. J., et al. (2020) · European Journal of Endocrinology · doi:10.1530/eje-20-0665 · Cited by 347 · see citing works
Liang, Y., Wang, M., Chien, C., Yarmishyn, A. A., Yang, Y.-P., Lai, W.-Y., Luo, Y., Lin, Y.-T., Chen, Y.-J., Chang, P., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01022 · Cited by 339 · see citing works
Immune-mediated approaches against COVID-19
Florindo, H. F., Kleiner, R., Vaskovich‐Koubi, D., Acúrcio, R. C., Carreira, B., Yeini, E., Tiram, G., Liubomirski, Y., & Satchi‐Fainaro, R. (2020) · Nature Nanotechnology · doi:10.1038/s41565-020-0732-3 · Cited by 342 · see citing works
Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection
Le Bert, N., Clapham, H. E., Tan, A. T., Chia, W. N., Tham, C. Y. L., Lim, J. M., Kunasegaran, K., Tan, L. W. L., Dutertre, C.-A., Shankar, N., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20202617 · Cited by 330 · see citing works
Ferretti, A. P., Kula, T., Wang, Y., Nguyen, D. M. V., Weinheimer, A., Dunlap, G. S., Xu, Q., Nabilsi, N., Perullo, C. R., Cristofaro, A. W., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.10.006 · Cited by 318 · see citing works
Cryo-EM structure of SARS-CoV-2 ORF3a in lipid nanodiscs
Kern, D. M., Sorum, B., Mali, S. S., Hoel, C., Sridharan, S., Remis, J. P., Toso, D. B., Kotecha, A., Bautista, D. M., & Brohawn, S. G. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-021-00619-0 · Cited by 316 · see citing works
Lessons for COVID-19 immunity from other coronavirus infections
Sariol, A., & Perlman, S. (2020) · Immunity · doi:10.1016/j.immuni.2020.07.005 · Cited by 317 · see citing works
Self-citationBarrett, J. R., Belij-Rammerstorfer, S., Dold, C., Ewer, K. J., Folegatti, P. M., Gilbride, C., Halkerston, R., Hill, J., Jenkin, D., Stockdale, L., et al. (2021) · Nature Medicine · doi:10.1038/s41591-020-01179-4 · Cited by 315 · see citing works
Two distinct immunopathological profiles in autopsy lungs of COVID-19
Nienhold, R., Ciani, Y., Koelzer, V. H., Tzankov, A., Haslbauer, J. D., Menter, T., Schwab, N., Henkel, M., Frank, A., Zsikla, V., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18854-2 · Cited by 246 · see citing works
Sun, L., Xing, Y., Chen, X., Zheng, Y., Yang, Y., Nichols, D. B., Clementz, M. A., Banach, B. S., Li, K., Baker, S. C., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030802 · Cited by 269 · see citing works
Prospects for a safe COVID-19 vaccine
Haynes, B. F., Corey, L., Fernandes, P., Gilbert, P. B., Hotez, P. J., Rao, S., Santos, M. R., Schuitemaker, H., Watson, M., & Arvin, A. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abe0948 · Cited by 261 · see citing works
Erasmus, J. H., Khandhar, A. P., O’Connor, M. A., Walls, A. C., Hemann, E. A., Murapa, P., Archer, J., Leventhal, S., Fuller, J. T., Lewis, T. B., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abc9396 · Cited by 241 · see citing works
SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors
Shomuradova, A. S., Vagida, M. S., Sheetikov, S. A., Zornikova, K. V., Kiryukhin, D. O., Titov, A., Peshkova, I. O., Khmelevskaya, A. A., Dianov, D. V., Malasheva, M., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.11.004 · Cited by 222 · see citing works
Feng, L.-Q., Wang, Q., Chao, S., Yang, C., Feng, Y., Wu, J., Liu, X., Zhou, Y., Jiang, R.-D., Hu, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18077-5 · Cited by 223 · see citing works
Self-citationIslam, M. T., Sarkar, C. K., El‐Kersh, D. M., Jamaddar, S., Uddin, S. J., Shilpi, J. A., & Mubarak, M. S. (2020) · Phytotherapy Research · doi:10.1002/ptr.6700 · Cited by 230 · see citing works
Tregoning, J. S., Brown, E. S., Cheeseman, H. M., Flight, K. E., Higham, S. L., Lemm, N.-M., Pierce, B. F., Stirling, D. C., Wang, Z., & Pollock, K. M. (2020) · Clinical & Experimental Immunology · doi:10.1111/cei.13517 · Cited by 222 · see citing works
Rokni, M., Ghasemi, V., & Tavakoli, Z. (2020) · Reviews in Medical Virology · doi:10.1002/rmv.2107 · Cited by 222 · see citing works
Coronaviruses: An Updated Overview of Their Replication and Pathogenesis
Wang, Y., Grunewald, M. E., & Perlman, S. M. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0900-2_1 · Cited by 207 · see citing works
Self-citationSARS–CoV-2–specific T cell responses and correlations with COVID-19 patient predisposition
Sattler, A., Angermair, S., Stockmann, H., Heim, K. M., Khadzhynov, D., Treskatsch, S., Halleck, F., Kreis, M. E., & Kotsch, K. (2020) · Journal of Clinical Investigation · doi:10.1172/jci140965 · Cited by 196 · see citing works
Viral Respiratory Pathogens and Lung Injury
Clementi, N., Ghosh, S., Santis, M. D., Castelli, M., Criscuolo, E., Zanoni, I., Clementi, M., & Mancini, N. (2021) · Clinical Microbiology Reviews · doi:10.1128/cmr.00103-20 · Cited by 191 · see citing works
Goyal, A., Ojeda, E. F. C., Fabian, E., & Schiffer, J. T. (2020) · Science Advances · doi:10.1126/sciadv.abc7112 · Cited by 183 · see citing works
Thieme, C. J., Anft, M., Paniskaki, K., Blazquez-Navarro, A., Doevelaar, A., Seibert, F. S., Hoelzer, B., Konik, M. J., Berger, M. M., Brenner, T., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100092 · Cited by 184 · see citing works
Neidleman, J., Luo, X., Frouard, J., Xie, G., Gill, G., Stein, E. S., McGregor, M., Ma, T., George, A. F., Kosters, A., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100081 · Cited by 188 · see citing works
Blood molecular markers associated with COVID‐19 immunopathology and multi‐organ damage
Chen, Y., Zheng, Y., Yu, Y., Wang, Y., Huang, Q., Qian, F., Sun, L., Song, Z., Chen, Z., Feng, J., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2020105896 · Cited by 183 · see citing works
Siegel, C. A., MELMED, G. Y., McGovern, D. P. B., Rai, V., Krammer, F., Rubin, D. T., Abreu, M. T., & Dubinsky, M. C. (2021) · Gut · doi:10.1136/gutjnl-2020-324000 · Cited by 179 · see citing works
Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains
Padron-Regalado, E. (2020) · Infectious Diseases and Therapy · doi:10.1007/s40121-020-00300-x · Cited by 178 · see citing works
Coronavirus virulence genes with main focus on SARS-CoV envelope gene
DeDiego, M. L., Nieto-Torres, J. L., Jiménez-Guardeño, J. M., Regla-Nava, J. Á., Castaño-Rodríguez, C., Fernández‐Delgado, R., Usera, F., & Enjuanes, L. (2014) · Virus Research · doi:10.1016/j.virusres.2014.07.024 · Cited by 174 · see citing works
Mapping and role of T cell response in SARS-CoV-2–infected mice
Zhuang, Z., Lai, X., Sun, J., Chen, Z., Zhang, Z., Dai, J., Liu, D., Li, Y., Li, F., Wang, Y., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20202187 · Cited by 171 · see citing works
Self-citationThe known unknowns of T cell immunity to COVID-19
Karlsson, A. C., Humbert, M., & Buggert, M. (2020) · Science Immunology · doi:10.1126/sciimmunol.abe8063 · Cited by 165 · see citing works
Vitamin D Regulation of Immune Function
Bikle, D. D. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00732-z · Cited by 179 · see citing works
Bilich, T., Nelde, A., Heitmann, J. S., Maringer, Y., Roerden, M., Bauer, J., Rieth, J., Wacker, M., Peter, A., Hörber, S., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abf7517 · Cited by 147 · see citing works
COVID 19: a clue from innate immunity
Birra, D., Benucci, M., Landolfi, L., Merchionda, A., Loi, G., Amato, P., Licata, G., Quartuccio, L., Triggiani, M., & Moscato, P. (2020) · Immunologic Research · doi:10.1007/s12026-020-09137-5 · Cited by 155 · see citing works
Jiménez-Guardeño, J. M., Regla-Nava, J. Á., Nieto-Torres, J. L., DeDiego, M. L., Castaño-Rodríguez, C., Fernández‐Delgado, R., Perlman, S. M., & Enjuanes, L. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1005215 · Cited by 156 · see citing works
Self-citationImmune responses during COVID-19 infection
Melenotte, C., Silvin, A., Goubet, A., Lahmar, I., Dubuisson, A., Zumla, A. I., Raoult, D., Merad-Boudia, M., Gachot, B., Henon, C., et al. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1807836 · Cited by 162 · see citing works
Hui, D. S. C. (2016) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2016.11.007 · Cited by 155 · see citing works
Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection
Files, J. K., Boppana, S., Perez, M. D., Sarkar, S., Lowman, K. E., Qin, K., Sterrett, S., Carlin, E., Bansal, A., Sabbaj, S., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci140491 · Cited by 155 · see citing works
Understanding the T cell immune response in SARS coronavirus infection
Oh, H. J., Gan, S. K., Bertoletti, A., & Tan, Y. (2012) · Emerging Microbes & Infections · doi:10.1038/emi.2012.26 · Cited by 152 · see citing works
Regla-Nava, J. Á., Nieto-Torres, J. L., Jiménez-Guardeño, J. M., Fernández‐Delgado, R., Fett, C., Castaño-Rodríguez, C., Perlman, S. M., Enjuanes, L., & DeDiego, M. L. (2015) · Journal of Virology · doi:10.1128/jvi.03566-14 · Cited by 152 · see citing works
Self-citationEstimation of SARS-CoV-2 Infection Fatality Rate by Real-time Antibody Screening of Blood Donors
Erikstrup, C., Hother, C., Pedersen, O. B., Mølbak, K., Skov, R. L., Holm, D. K., Sækmose, S. G., Nilsson, A. C., Brooks, P. T., Boldsen, J. K., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa849 · Cited by 148 · see citing works
Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19
Hou, H., Zhang, B., Huang, H., Luo, Y., Wu, S., Tang, G., Liu, W., Mao, L., Mao, L., Wang, F., et al. (2020) · Clinical & Experimental Immunology · doi:10.1111/cei.13450 · Cited by 145 · see citing works
Lymphopenia an important immunological abnormality in patients with COVID‐19: Possible mechanisms
Jafarzadeh, A., Jafarzadeh, S., Nozari, P., Mokhtari, P., & Nemati, M. (2020) · Scandinavian Journal of Immunology · doi:10.1111/sji.12967 · Cited by 146 · see citing works
The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19)
Domingo, P., Mur, I., Pomar, V., Corominas, H., Casademont, J., & Benito, N. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102887 · Cited by 168 · see citing works
Intranasal Treatment with Poly(I·C) Protects Aged Mice from Lethal Respiratory Virus Infections
Zhao, J., Wohlford-Lenane, C., Zhao, J., Fleming, E., Lane, T. E., McCray, P. B., & Perlman, S. M. (2012) · Journal of Virology · doi:10.1128/jvi.01410-12 · Cited by 140 · see citing works
Self-citationMinervina, A. A., Komech, E. A., Titov, A., Koraichi, M. B., Rosati, E., Mamedov, I. Z., Franke, A., Efimov, G. A., Chudakov, D. M., Mora, T., et al. (2021) · eLife · doi:10.7554/elife.63502 · Cited by 141 · see citing works
Aleebrahim‐Dehkordi, E., Molavi, B., Mokhtari, M., Deravi, N., Fathi, M., Fazel, T., Mohebalizadeh, M., Koochaki, P., Shobeiri, P., & Dehkordi, A. H. (2021) · Transplant Immunology · doi:10.1016/j.trim.2021.101495 · Cited by 129 · see citing works
Does infection with or vaccination against SARS-CoV-2 lead to lasting immunity?
Milne, G., Hames, T., Scotton, C. J., Gent, N., Johnsen, A., Anderson, R. M., & Ward, T. (2021) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(21)00407-0 · Cited by 121 · see citing works
Count on us: T cells in SARS-CoV-2 infection and vaccination
Kedzierska, K., & Thomas, P. G. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100562 · Cited by 124 · see citing works
Ding, T., Zhang, J., Wang, T., Cui, P., Chen, Z., Jiang, J., Zhou, S., Dai, J., Wang, B., Yuan, S., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1022 · Cited by 124 · see citing works
Particulate Alum via Pickering Emulsion for an Enhanced COVID‐19 Vaccine Adjuvant
Peng, S., Cao, F., Xia, Y., Gao, X., Dai, L., Yan, J., & Ma, G. (2020) · Advanced Materials · doi:10.1002/adma.202004210 · Cited by 123 · see citing works
Sacchi, A., Grassi, G., Bordoni, V., Lorenzini, P., Cimini, E., Casetti, R., Tartaglia, E., Marchioni, L., Petrosillo, N., Palmieri, F., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03125-1 · Cited by 115 · see citing works
Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients
Liu, X., Zhu, A., He, J., Chen, Z., Lin, L., 徐远达, Ye, F., Feng, H., Luo, L., Cai, B., et al. (2020) · Protein & Cell · doi:10.1007/s13238-020-00752-4 · Cited by 110 · see citing works
Self-citationSARS-CoV-2 Vaccine Development: Current Status
Poland, G. A., Ovsyannikova, I. G., Crooke, S. N., & Kennedy, R. B. (2020) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2020.07.021 · Cited by 112 · see citing works
T cell immunity to SARS-CoV-2 following natural infection and vaccination
DiPiazza, A. T., Graham, B. S., & Ruckwardt, T. J. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.10.060 · Cited by 107 · see citing works
The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2
Chow, R. D.-W., Majety, M., & Chen, S. (2021) · Nature Communications · doi:10.1038/s41467-020-20323-9 · Cited by 104 · see citing works
Viral Vector Vaccine Development and Application during the COVID-19 Pandemic
Deng, S., Liang, H., Pin, C., Li, Y., Li, Z., Fan, S., Wu, K., Li, X., Chen, W., Qin, Y., et al. (2022) · Microorganisms · doi:10.3390/microorganisms10071450 · Cited by 107 · see citing works
Corticosteroid administration for viral pneumonia: COVID-19 and beyond
Yang, J., Yang, L., Luo, R.-G., & Xu, J. (2020) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2020.06.020 · Cited by 106 · see citing works
Hogan, R. B., Hogan, R. B., Cannon, T., Rappai, M., Studdard, J., Paul, D., & Dooley, T. P. (2020) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2020.101942 · Cited by 104 · see citing works
Approaches and Challenges in SARS-CoV-2 Vaccine Development
Dagotto, G., Yu, J., & Barouch, D. H. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.08.002 · Cited by 103 · see citing works
Poran, A., Harjanto, D., Malloy, M., Arieta, C. M., Rothenberg, D. A., Lenkala, D., van Buuren, M. M., Addona, T. A., Rooney, M. S., Srinivasan, L., et al. (2020) · Genome Medicine · doi:10.1186/s13073-020-00767-w · Cited by 102 · see citing works
Tse, L. V., Meganck, R. M., Graham, R. L., & Baric, R. S. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00658 · Cited by 99 · see citing works
Zhang, Y.-Y., Li, B.-R., & Ning, B. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02033 · Cited by 103 · see citing works
COVID-19 preclinical models: human angiotensin-converting enzyme 2 transgenic mice
Lutz, C. M., Maher, L. A., Lee, C., & Kang, W. (2020) · Human Genomics · doi:10.1186/s40246-020-00272-6 · Cited by 92 · see citing works
- Authors
- Zhao, J., Zhao, J., & Perlman, S.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Perlman, Stanley
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2010-09-15
- Volume
- 84
- Issue
- 18
- Pages
- 9318-9325
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2937604
- OpenAlex
- W1999546368
- Cited by
- 340
- References
- 36
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 10 · 2023: 28 · 2022: 52 · 2021: 76 · 2020: 122 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 11 · 2015: 4 · 2014: 9 · 2013: 2 · 2012: 4
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (PO1AI060699, AI060699)
- National Institute of Allergy and Infectious Diseases (R21AI079429, R56AI079429, P01AI060699)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Keywords
- SARS, SARS-CoV, T cell response, CD8+ T cells, viral clearance, adoptive T cell therapy, dendritic cell immunization, innate immune response, lung viral titers, SARS pathogenesis
- MeSH terms
- Animals, Lung, Mice, Inbred BALB C, Spleen, T-Lymphocytes, Viral Vaccines, Survival Analysis, Mice, SCID, Adoptive Transfer, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
