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Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection.
Clin Infect Dis. 2019 03 05; 68(6):984-992.CI

Abstract

BACKGROUND

An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection.

METHODS

We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with overlapping peptides spanning whole virus structural proteins.

RESULTS

At the acute phase of infection, elevated levels of plasma proinflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS coronavirus-reactive CD8+ T cells were also observed in patients with severe/moderate illness, whereas antibody and CD4+ T-cell responses were minimally detected at this stage. At the convalescent phase, disease severity-dependent antibody responses emerged and antigen-reactive cells were identified in both T-cell subsets. These T cells belonged to the T-helper 1 or type 1 cytotoxic T cell subtypes. While CD8+ T cells responded preferentially to the viral S protein compared with E/M/N proteins, especially at the acute stage, slightly more CD4+ T cells recognized E/M/N proteins compared with S protein at the convalescent phase.

CONCLUSIONS

Our findings show an association between the early CD8+ T-cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans.

Authors+Show Affiliations

Center for Infectious Diseases, Department of Internal Medicine.Center for Infectious Diseases, Department of Internal Medicine.Center for Infectious Diseases, Department of Internal Medicine.Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine.Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine.Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine.Center for Chronic Diseases, Research Institute, National Medical Center, Seoul, Korea.Center for Chronic Diseases, Research Institute, National Medical Center, Seoul, Korea.Center for Chronic Diseases, Research Institute, National Medical Center, Seoul, Korea.Center for Infectious Diseases, Research Institute, National Medical Center, Seoul, Korea.Center for Chronic Diseases, Research Institute, National Medical Center, Seoul, Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30060038

Citation

Shin, Hyoung-Shik, et al. "Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 68, no. 6, 2019, pp. 984-992.
Shin HS, Kim Y, Kim G, et al. Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection. Clin Infect Dis. 2019;68(6):984-992.
Shin, H. S., Kim, Y., Kim, G., Lee, J. Y., Jeong, I., Joh, J. S., Kim, H., Chang, E., Sim, S. Y., Park, J. S., & Lim, D. G. (2019). Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 68(6), 984-992. https://doi.org/10.1093/cid/ciy595
Shin HS, et al. Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection. Clin Infect Dis. 2019 03 5;68(6):984-992. PubMed PMID: 30060038.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection. AU - Shin,Hyoung-Shik, AU - Kim,Yeonjae, AU - Kim,Gayeon, AU - Lee,Ji Yeon, AU - Jeong,Ina, AU - Joh,Joon-Sung, AU - Kim,Hana, AU - Chang,Eunjin, AU - Sim,Soo Yeon, AU - Park,Jun-Sun, AU - Lim,Dong-Gyun, PY - 2018/02/01/received PY - 2018/07/25/accepted PY - 2018/7/31/pubmed PY - 2020/5/2/medline PY - 2018/7/31/entrez KW - MERS coronavirus KW - T lymphocytes KW - acute phase of infection KW - immune response SP - 984 EP - 992 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin Infect Dis VL - 68 IS - 6 N2 - BACKGROUND: An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection. METHODS: We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with overlapping peptides spanning whole virus structural proteins. RESULTS: At the acute phase of infection, elevated levels of plasma proinflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS coronavirus-reactive CD8+ T cells were also observed in patients with severe/moderate illness, whereas antibody and CD4+ T-cell responses were minimally detected at this stage. At the convalescent phase, disease severity-dependent antibody responses emerged and antigen-reactive cells were identified in both T-cell subsets. These T cells belonged to the T-helper 1 or type 1 cytotoxic T cell subtypes. While CD8+ T cells responded preferentially to the viral S protein compared with E/M/N proteins, especially at the acute stage, slightly more CD4+ T cells recognized E/M/N proteins compared with S protein at the convalescent phase. CONCLUSIONS: Our findings show an association between the early CD8+ T-cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/30060038/full_citation L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciy595 DB - PRIME DP - Unbound Medicine ER -