Thursday, June 6, 2013

ProMED: MERS-CoV - Eastern Mediterranean (21): receptor identification #MERS #Coronavirus

Published Date: 2013-06-05 12:58:40
Archive Number: 20130605.1756082

Date: Wed 5 Jun 2013
From: Bart Haagmans <> [edited]
Tim Sly suggests in a recent ProMED-mail post [MERS-CoV - Eastern Mediterranean (19): receptor specificity, RFI 20130604.175462] that: "The recent observation that upper respiratory tract (URT) swabs may not contain MERS-CoV, while the lower respiratory tract (LRT) can harbour the virus in the same patients, suggests an hypothesis that infection by MERS-CoV may be dependent on the variety of neuraminidase-linked sialic acid at receptor sites in respiratory epithelium, as is widely recognized in avian influenza [AI] virus."

In fact, recently, a group of scientists from the Netherlands, Germany, and Switzerland have identified dipeptidyl peptidase 4 as a functional receptor for MERS-CoV. This receptor indeed is mainly found in the lower respiratory tract on non-ciliated bronchial cells but not on ciliated cells that are more common in the upper respiratory tract, consistent with the observation that MERS-CoV mainly is detected in LRT of patients infected with MERS-CoV. Additionally, other investigators have shown that type 2 pneumocytes are targeted by the virus. Thus far there is no evidence for other receptors involved in entry of MERS-CoV.

The following is the abstract of the paper by Raj et al (Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC, Nature, 495: 251-4, 14 Mar 2013

"Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals. However, SARS coronavirus caused severe lower respiratory disease with nearly 10 percent mortality and evidence of systemic spread. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC) [now designated MERS-CoV] was identified in patients with severe and sometimes lethal lower respiratory tract infection. Viral genome analysis revealed close relatedness to coronaviruses found in bats. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (_Pipistrellus pipistrellus_) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoVEMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies."

Bart Haagmans
Department of Viroscience
Erasmus Medical Center
The Netherlands

[ProMED-mail thanks Bart Haagmans for providing this prompt response to Tim Sly's request for information, and similarly to Debora MacKenzie, Brussels Office, New Scientist, for also drawing our attention to the recently published Nature paper, summarised above. - Mod.CP]

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