Media Releases

Researchers map pathway of infection for a common, potentially life-threatening respiratory virus

August 15, 2011

TORONTO, ON — Researchers at the Uni­ver­si­ty of Toron­to, The Hos­pi­tal for Sick Chil­dren (Sick­Kids), St. Paul’s Hos­pi­tal and the Uni­ver­si­ty of British Colum­bia have iden­ti­fied a new treat­ment tar­get for a virus that caus­es severe lung infec­tions and an esti­mat­ed 10% of com­mon colds.

The virus, called human res­pi­ra­to­ry syn­cy­tial virus or RSV, is the most com­mon rea­son for hos­pi­tal­iza­tion of infants and chil­dren under two years of age; cur­rent­ly there is no effec­tive ther­a­py or vac­cine for it.

“This dis­cov­ery pro­vides an under­stand­ing of the mech­a­nism through which RSV caus­es infec­tion and offers a tar­get mol­e­cule for devel­op­ment of new cell-based ther­a­pies,” said the study’s prin­ci­pal inves­ti­ga­tor Prof. Richard Hegele, Chair and Pro­fes­sor in U of T’s Depart­ment of Lab­o­ra­to­ry Med­i­cine and Patho­bi­ol­o­gy who is also Chief of Pae­di­atric Lab­o­ra­to­ry Med­i­cine at Sick­Kids.

The research is pub­lished in the cur­rent edi­tion of the jour­nal Nature Med­i­cine.

The researchers found that RSV inter­acts with healthy cells by bind­ing with a mol­e­cule locat­ed on the sur­face of those cells called nucle­olin. By manip­u­lat­ing the func­tion of nucle­olin in cell cul­ture, they were able to decrease RSV infec­tion or increase sus­cep­ti­bil­i­ty to it.

In mice, the researchers showed that dis­rup­tion of lung nucle­olin was asso­ci­at­ed with sig­nif­i­cant­ly reduced RSV infec­tion, con­firm­ing that the mol­e­cule is a viable ther­a­peu­tic tar­get.

“While oth­er fac­tors may influ­ence the fre­quen­cy and sever­i­ty of RSV infec­tions, our results indi­cate that the pres­ence of nucle­olin on the cell sur­face is suf­fi­cient for RSV to suc­cess­ful­ly infect cells,” said Hegele. “We can now pur­sue strate­gies designed to block the inter­ac­tion of RSV with cell sur­face nucle­olin, the idea being to find approach­es that will safe­ly and effec­tive­ly halt infec­tion by pre­vent­ing RSV from enter­ing the cell in the first place.”

Researchers have been search­ing for a recep­tor for RSV for over five decades.

“This is a long-await­ed and much-need­ed dis­cov­ery that will help researchers devel­op new ther­a­pies for this dis­ease, which has a large glob­al bur­den, pri­mar­i­ly affect­ing young chil­dren and oth­er vul­ner­a­ble pop­u­la­tions,” said Dr. David Marchant, a research asso­ciate at UBC’s James Hogg iCAP­TURE Cen­tre at St. Paul’s Hos­pi­tal, and co-lead on the study. “What is espe­cial­ly encour­ag­ing is that there is already a lot of ground work done in terms of under­stand­ing the biol­o­gy of nucle­olin to treat oth­er ail­ments like can­cer. The dis­cov­ery of the RSV recep­tor com­bined with this knowl­edge could help deliv­er a poten­tial ther­a­peu­tic much faster.”

Increas­ing­ly, RSV is being rec­og­nized as a seri­ous pathogen of the elder­ly for caus­ing lung infec­tions such as pneu­mo­nia. It is also a com­mon cause of mid­dle ear infec­tions and can infect oth­er organ sys­tems, and has been impli­cat­ed in the onset of asth­ma and aller­gy in chil­dren. Organ trans­plant recip­i­ents or oth­er indi­vid­u­als whose immune sys­tems are com­pro­mised are also at increased risk for seri­ous RSV lung infec­tions.

Accord­ing to the World Health Orga­ni­za­tion, the glob­al RSV dis­ease bur­den is esti­mat­ed at 64 mil­lion cas­es and 160,000 deaths each year. It is con­sid­ered the sin­gle most impor­tant cause of severe res­pi­ra­to­ry ill­ness in infants and young chil­dren.¹

The study was con­duct­ed by the fol­low­ing researchers: Richard G. Hegele (Uni­ver­si­ty of Toron­to Depart­ment of Lab­o­ra­to­ry Med­i­cine and Patho­bi­ol­o­gy, and The Hos­pi­tal for Sick Chil­dren (Sick­Kids)); Farnoosh Tay­yari and David Marchant (James Hogg iCAP­TURE Cen­tre at St. Paul’s Hos­pi­tal and UBC Depart­ment of Pathol­o­gy and Lab­o­ra­to­ry Med­i­cine); Theo J. Moraes (U of T and Sick­Kids); Wen­ming Duan (Sick­Kids); Peter Mas­trange­lo (U of T).

Fund­ing for the study was pro­vid­ed by the Cana­di­an Insti­tutes of Health Research and the Heart and Stroke Foun­da­tion of British Colum­bia.

1 World Health Orga­ni­za­tion 2009 http://www.who.int/vaccine_research/diseases/ari/en/index2.html

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For more infor­ma­tion, please con­tact:

Jim Old­field
Uni­ver­si­ty of Toron­to Temer­ty Temer­ty Fac­ul­ty of Med­i­cine
416–946-8423
jim.oldfield@utoronto.ca
www.facmed.utoronto.ca
http://twitter.com/#!/uoftmedicine

Caitlin McNamee-Lamb
The Hos­pi­tal for Sick Chil­dren
416–813-7654, ext. 1436
caitlin.mcnamee-lamb@sickkids.ca

Bri­an Lin
Uni­ver­si­ty of British Colum­bia
Office: 604–822-2064
Cell: 604–818-5685
brian.lin@ubc.ca