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Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development

Identifieur interne : 000244 ( Pmc/Checkpoint ); précédent : 000243; suivant : 000245

Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development

Auteurs : Ayman Mubarak [Arabie saoudite] ; Wael Alturaiki [Arabie saoudite] ; Maged Gomaa Hemida [Arabie saoudite, Égypte]

Source :

RBID : PMC:6476043

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in late 2012. Since its emergence, a total of 2279 patients from 27 countries have been infected across the globe according to a World Health Organization (WHO) report (Feb. 12th, 2019). Approximately 806 patients have died. The virus uses its spike proteins as adhesive factors that are proinflammatory for host entry through a specific receptor called dipeptidyl peptidase-4 (DPP4). This receptor is considered a key factor in the signaling and activation of the acquired and innate immune responses in infected patients. Using potent antigens in combination with strong adjuvants may effectively trigger the activation of specific MERS-CoV cellular responses as well as the production of neutralizing antibodies. Unfortunately, to date, there is no effective approved treatment or vaccine for MERS-CoV. Thus, there are urgent needs for the development of novel MERS-CoV therapies as well as vaccines to help minimize the spread of the virus from infected patients, thereby mitigating the risk of any potential pandemics. Our main goals are to highlight and describe the current knowledge of both the innate and adaptive immune responses to MERS-CoV and the current state of MERS-CoV vaccine development. We believe this study will increase our understanding of the mechanisms that enhance the MERS-CoV immune response and subsequently contribute to the control of MERS-CoV infections.


Url:
DOI: 10.1155/2019/6491738
PubMed: 31089478
PubMed Central: 6476043


Affiliations:


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PMC:6476043

Le document en format XML

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<pmc article-type="review-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">J Immunol Res</journal-id>
<journal-id journal-id-type="iso-abbrev">J Immunol Res</journal-id>
<journal-id journal-id-type="publisher-id">JIR</journal-id>
<journal-title-group>
<journal-title>Journal of Immunology Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">2314-8861</issn>
<issn pub-type="epub">2314-7156</issn>
<publisher>
<publisher-name>Hindawi</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">31089478</article-id>
<article-id pub-id-type="pmc">6476043</article-id>
<article-id pub-id-type="doi">10.1155/2019/6491738</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0003-4948-5574</contrib-id>
<name>
<surname>Mubarak</surname>
<given-names>Ayman</given-names>
</name>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-6947-7582</contrib-id>
<name>
<surname>Alturaiki</surname>
<given-names>Wael</given-names>
</name>
<email>w.alturaiki@mu.edu.sa</email>
<xref ref-type="aff" rid="I2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-5986-7237</contrib-id>
<name>
<surname>Hemida</surname>
<given-names>Maged Gomaa</given-names>
</name>
<xref ref-type="aff" rid="I3">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="I4">
<sup>4</sup>
</xref>
</contrib>
</contrib-group>
<aff id="I1">
<sup>1</sup>
Department of Botany and Microbiology, College of Science, King Saud University, Saudi Arabia</aff>
<aff id="I2">
<sup>2</sup>
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia</aff>
<aff id="I3">
<sup>3</sup>
Department of Microbiology and Parasitology, College of Veterinary Medicine, King Faisal University, Saudi Arabia</aff>
<aff id="I4">
<sup>4</sup>
Department of Virology, Faculty of Veterinary Medicine, Kafresheikh University, Egypt</aff>
<author-notes>
<fn fn-type="other">
<p>Academic Editor: Isabella Quinti</p>
</fn>
</author-notes>
<pub-date pub-type="collection">
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>7</day>
<month>4</month>
<year>2019</year>
</pub-date>
<volume>2019</volume>
<elocation-id>6491738</elocation-id>
<history>
<date date-type="received">
<day>29</day>
<month>11</month>
<year>2018</year>
</date>
<date date-type="rev-recd">
<day>20</day>
<month>2</month>
<year>2019</year>
</date>
<date date-type="accepted">
<day>20</day>
<month>2</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2019 Ayman Mubarak et al.</copyright-statement>
<copyright-year>2019</copyright-year>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract>
<p>Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in late 2012. Since its emergence, a total of 2279 patients from 27 countries have been infected across the globe according to a World Health Organization (WHO) report (Feb. 12th, 2019). Approximately 806 patients have died. The virus uses its spike proteins as adhesive factors that are proinflammatory for host entry through a specific receptor called dipeptidyl peptidase-4 (DPP4). This receptor is considered a key factor in the signaling and activation of the acquired and innate immune responses in infected patients. Using potent antigens in combination with strong adjuvants may effectively trigger the activation of specific MERS-CoV cellular responses as well as the production of neutralizing antibodies. Unfortunately, to date, there is no effective approved treatment or vaccine for MERS-CoV. Thus, there are urgent needs for the development of novel MERS-CoV therapies as well as vaccines to help minimize the spread of the virus from infected patients, thereby mitigating the risk of any potential pandemics. Our main goals are to highlight and describe the current knowledge of both the innate and adaptive immune responses to MERS-CoV and the current state of MERS-CoV vaccine development. We believe this study will increase our understanding of the mechanisms that enhance the MERS-CoV immune response and subsequently contribute to the control of MERS-CoV infections.</p>
</abstract>
<funding-group>
<award-group>
<funding-source>Majmaah University</funding-source>
<award-id>1440-1</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
<floats-group>
<fig id="fig1" orientation="portrait" position="float">
<label>Figure 1</label>
<caption>
<p>The proposed schematic representation of the immune response to MERS-CoV infection and how the invading virus is processed during an infection. (1) MERS-CoV infects macrophages through DPP4 binding, and then macrophages present MERS-CoV antigens to Th0 cells. This process leads to T cell activation and differentiation, including the production of cytokines associated with the different T cell subsets (i.e., Th1, Th2, and Th17), followed by a massive release of cytokines for immune response amplification. The continued production of these mediators due to viral persistence has a negative effect on Th0, NK, and CD8 T cell activation by inhibiting IL12 and IFN-
<italic>γ</italic>
production. However, CD8 T cells produce very effective mediators, such as IFN-
<italic>γ</italic>
and granzyme, to clear MERS-CoV. It is still unclear whether long-term or short-term protective antibodies are produced during neutralizing antibody production against MERS-CoV. (2) Attachment of MERS-CoV to DPP4 on the host cell through S protein leads to the appearance of genomic RNA in the cytoplasm. An immune response to dsRNA can be partially generated during MERS-CoV replication. TLR-3 sensitized by dsRNA and cascades of signaling pathways (IRFs and NF-
<italic>κ</italic>
B activation via TRAF3 and TRAF6, respectively) are activated to produce type I IFNs and proinflammatory cytokines. The production of type I IFNs is important to enhance the release of antiviral proteins for the protection of uninfected cells. Sometimes, accessory proteins of MERS-CoV can interfere with TLR-3 signaling and bind the dsRNA of MERS-CoV during replication to prevent TLR-3 activation and evade the immune response. TLR-4 might recognize S protein and lead to the activation of proinflammatory cytokines through the MyD88-dependent signaling pathway. Virus-cell interactions lead to strong production of immune mediators. The secretion of large quantities of chemokines and cytokines (MCP-1, IL10, and CXCL10) is promoted in infected cells in response to MERS-CoV infection. These chemokines and cytokines in turn recruit lymphocytes and leukocytes to the site of infection. Red arrows refer to inhibitory effects. Black arrows refer to activating effects.</p>
</caption>
<graphic xlink:href="JIR2019-6491738.001"></graphic>
</fig>
</floats-group>
</pmc>
<affiliations>
<list>
<country>
<li>Arabie saoudite</li>
<li>Égypte</li>
</country>
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<country name="Arabie saoudite">
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<name sortKey="Mubarak, Ayman" sort="Mubarak, Ayman" uniqKey="Mubarak A" first="Ayman" last="Mubarak">Ayman Mubarak</name>
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<name sortKey="Alturaiki, Wael" sort="Alturaiki, Wael" uniqKey="Alturaiki W" first="Wael" last="Alturaiki">Wael Alturaiki</name>
<name sortKey="Hemida, Maged Gomaa" sort="Hemida, Maged Gomaa" uniqKey="Hemida M" first="Maged Gomaa" last="Hemida">Maged Gomaa Hemida</name>
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<name sortKey="Hemida, Maged Gomaa" sort="Hemida, Maged Gomaa" uniqKey="Hemida M" first="Maged Gomaa" last="Hemida">Maged Gomaa Hemida</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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