SARS-like virus targets cells in human airway

N. Gopal Raj
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The virus actually targets the lower respiratory tract in humans

Modus operandi:Viruses need to enter cells and hijack their molecular machinery in order to replicate and spread.— photo: AP
Modus operandi:Viruses need to enter cells and hijack their molecular machinery in order to replicate and spread.— photo: AP

A virus that emerged in the Middle East last year, causing severe respiratory problems, kidney failure and even death among many persons it infected, was gaining entry by latching on to a molecule found on the surface of certain cells deep in the human airway, according to a team of scientists whose research appears in this week's issue of the journal Nature .

Their discovery opens the way to uncovering key aspects about how the virus is transmitted and produces disease as well as of finding ways to treat those affected by it.

The virus was first detected in sputum samples taken from a 60-year-old man hospitalised in Saudi Arabia last June with pneumonia and kidney failure, who later died. There have been 15 confirmed cases of human infection with this virus, with nine deaths, reported from Saudi Arabia, Jordan, Qatar and Britain, according to the World Health Organisation.

Virologists at the Erasmus Medical Centre in the Netherlands, who isolated and characterised the microbe, found that it was a novel coronavirus. As the outbreak of ‘severe acute respiratory syndrome’ (SARS), which began in southern China in 2002 and then suddenly exploded across the world the following year, had also been caused by a coronavirus, the discovery of this new pathogen sparked considerable concern among public health professionals.

In their Nature paper, the Erasmus Medical Centre team, along with their collaborators, have reported that the new coronavirus, given the designation hCoV-EMC, was using the protein ‘dipeptidyl peptidase 4’ (DPP4, also known as CD26) as a receptor to latch on to cells lining the respiratory tract and infect them. Viruses need to enter cells and hijack their molecular machinery in order to replicate and spread.

“The identification of the receptor for this novel coronavirus provides evidence that the virus actually targets the lower respiratory tract in humans,” said Bart L. Haagmans, senior author of the paper, in an email.

Cells with the DPP4 receptor being more abundant in the lower respiratory tract “could be one of the reasons there is limited transmission of this virus [among people],” noted V. Stalin Raj, the paper's first author who is part of the Erasmus Medical Centre group. If, on the other hand, virus replication had been taking place in the upper respiratory tract, it might have been able to transmit more quickly from person to person, he told this correspondent.

Now that the receptor had been identified, the next step would be to use animals, such as ferrets, to study which other cells and tissues in the body the virus was infecting, the mechanisms by which it caused disease and how it was able to spread, remarked Dr. Raj.

Dr Raj hails from Tamil Nadu and did his doctoral research at the Central Institute of Brackishwater Aquaculture in Chennai before moving to Europe.

As with the SARS virus, the new hCoV-EMC coronavirus appears to have originated in bats. However, unlike the former, the latter is still able to infect bat cells. Moreover, the structure of the DPP4 receptor has been evolutionarily conserved in many different animals.

“The interesting and perhaps troubling findings from studies of this virus thus far are that there may be a plethora of sources for its intrusion into the human population,” remarked Tom Gallagher and Stanley Perlman in a commentary on the paper published in the same issue of the journal. More work was needed to address this issue.



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