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J Virol. Receptor variation and susceptibility to MERS coronavirus infection
[Source: Journal of Virology, full page: (LINK). Abstract, edited.]
Receptor variation and susceptibility to MERS coronavirus infection
Arlene Barlan 1, Jincun Zhao 2, Mayukh K. Sarkar 1, Kun Li 3, Paul B. McCray Jr. 3, Stanley Perlman 2 and Tom Gallagher 1
Author Affiliations: <SUP>1</SUP>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL, 60153 - Departments of<SUP>2</SUP>Microbiology - <SUP>3</SUP>Pediatrics, University of Iowa, Iowa City, IA, 52242
Published ahead of print 19 February 2014, doi: 10.1128/JVI.00161-14 <CITE>JVI.00161-14 </CITE>
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<CITE></CITE>ABSTRACT
The Middle East Respiratory Syndrome coronavirus (MERS-CoV) recently spread from an animal reservoir to infect humans, causing sporadic severe, and frequently fatal respiratory disease. Appropriate public health and control measures will require discovery of the zoonotic MERS coronavirus reservoirs. The relevant animal hosts are liable to be those that offer optimal MERS virus-cell entry. Cell entry begins with virus spike (S) protein binding to DPP4 receptors. We constructed chimeric DPP4 receptors that have the virus-binding domains of indigenous Middle Eastern animals, and assessed the activities of these receptors in supporting S protein binding and virus entry. Human, camel, and horse receptors were potent and nearly equally effective MERS virus receptors, while goat and bat receptors were considerably less effective. These patterns reflected S protein affinities for the receptors. However, even the low-affinity receptors could hyper-sensitize cells to infection when S-cleaving protease(s) were present, indicating that affinity thresholds for virus entry must be considered in the context of host-cell proteolytic environments. These findings suggest that virus receptors and S protein-cleaving proteases combine in a variety of animals to offer efficient virus entry, and that several Middle Eastern animals are potential reservoirs for transmitting MERS-CoV to humans.
Importance
Middle East Respiratory Syndrome (MERS) is a frequently fatal disease that is caused by a zoonotic coronavirus (CoV). The animals transmitting MERS-CoV to humans are not yet known. Infection by MERS-CoV requires receptors and proteases on host cells. We compared the receptors of humans and Middle Eastern animals, and found that human, camel and horse receptors sensitized cells to MERS-CoV infection more robustly than goat and bat receptors. Infection susceptibility correlated with affinities of the receptors for viral spike proteins. We also found that the presence of a cell-surface lung protease will greatly increase susceptibility to MERS-CoV, particularly in conjunction with low-affinity receptors. This cataloguing of human and animal host cell factors allows one to make inferences on the distribution of MERS-CoV in nature.
FOOTNOTES
To whom correspondence should be addressed. E-mail: tgallag@lumc.edu
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
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Receptor variation and susceptibility to MERS coronavirus infection
Arlene Barlan 1, Jincun Zhao 2, Mayukh K. Sarkar 1, Kun Li 3, Paul B. McCray Jr. 3, Stanley Perlman 2 and Tom Gallagher 1
Author Affiliations: <SUP>1</SUP>Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL, 60153 - Departments of<SUP>2</SUP>Microbiology - <SUP>3</SUP>Pediatrics, University of Iowa, Iowa City, IA, 52242
Published ahead of print 19 February 2014, doi: 10.1128/JVI.00161-14 <CITE>JVI.00161-14 </CITE>
<CITE></CITE>
<CITE></CITE>
<CITE></CITE>ABSTRACT
The Middle East Respiratory Syndrome coronavirus (MERS-CoV) recently spread from an animal reservoir to infect humans, causing sporadic severe, and frequently fatal respiratory disease. Appropriate public health and control measures will require discovery of the zoonotic MERS coronavirus reservoirs. The relevant animal hosts are liable to be those that offer optimal MERS virus-cell entry. Cell entry begins with virus spike (S) protein binding to DPP4 receptors. We constructed chimeric DPP4 receptors that have the virus-binding domains of indigenous Middle Eastern animals, and assessed the activities of these receptors in supporting S protein binding and virus entry. Human, camel, and horse receptors were potent and nearly equally effective MERS virus receptors, while goat and bat receptors were considerably less effective. These patterns reflected S protein affinities for the receptors. However, even the low-affinity receptors could hyper-sensitize cells to infection when S-cleaving protease(s) were present, indicating that affinity thresholds for virus entry must be considered in the context of host-cell proteolytic environments. These findings suggest that virus receptors and S protein-cleaving proteases combine in a variety of animals to offer efficient virus entry, and that several Middle Eastern animals are potential reservoirs for transmitting MERS-CoV to humans.
Importance
Middle East Respiratory Syndrome (MERS) is a frequently fatal disease that is caused by a zoonotic coronavirus (CoV). The animals transmitting MERS-CoV to humans are not yet known. Infection by MERS-CoV requires receptors and proteases on host cells. We compared the receptors of humans and Middle Eastern animals, and found that human, camel and horse receptors sensitized cells to MERS-CoV infection more robustly than goat and bat receptors. Infection susceptibility correlated with affinities of the receptors for viral spike proteins. We also found that the presence of a cell-surface lung protease will greatly increase susceptibility to MERS-CoV, particularly in conjunction with low-affinity receptors. This cataloguing of human and animal host cell factors allows one to make inferences on the distribution of MERS-CoV in nature.
FOOTNOTES
To whom correspondence should be addressed. E-mail: tgallag@lumc.edu
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
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