Exploiting Pathway in Host Cells May Combat Emerging Viral Infections

MedicalResearch.com Interview with:

MedicalResearch.com Interview with: Dr. Cameron Stewart PhD Team Leader within the Emerging Infectious Diseases Program CSIRO Biosecurity Flagship Commonwealth Scientific and Industrial Research Organisation

Dr. Cameron Stewart

Dr. Cameron Stewart PhD
Team Leader within the Emerging Infectious Diseases Program
CSIRO Biosecurity Flagship
Commonwealth Scientific and Industrial Research Organisation

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Stewart: Hendra and Nipah viruses (referred to jointly as henipaviruses) are deadly cousins of the more common mumps, measles, and respiratory syncytial viruses, all members of the paramyxovirus family. Henipavirus outbreaks are on the rise, but little is known about the viruses, partly because research has to be undertaken under extreme containment conditions.  Our team performs research at the largest high containment facility in the Asia-Pacific region, the CSIRO Australian Animal Health Laboratory in Geelong, Australia.

To understand the henipavirus infection cycle and to identify targets for new antiviral therapies, we performed a genome-wide screen to identify the host molecules required by henipaviruses for infection. The host gene with the largest impact, called fibrillarin, codes for a protein present in the nucleolus. Inhibiting fibrillarin impaired henipavirus infection greater than 1,000-fold in human cells.  We examined closely which step of the viral life cycle was blocked by interfering with fibrillarin function, and found it was required for the early synthesis of viral RNA. Results from our study suggest that fibrillarin could be targeted therapeutically to combat henipavirus infections. This research was undertaken by an international team of researchers from CSIRO, the Victorian Centre for Functional Genomics, Duke-NUS, the University of Georgia and the Centers for Disease Control and Prevention.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Stewart: Viruses from the family Paramyxoviridae are highly important pathogens impacting human health, collectively causing hundreds of thousands of deaths globally each year. There are limited vaccines or therapies to treat paramyxovirus infections in humans and many aspects of paramyxovirus pathogenesis remain poorly understood.

Viruses are often unable to cause infection and disease without exploiting pathways within a host cell. Learning which host molecules are required for infection not only furthers understanding of virus biology, it also identifies targets for antiviral therapeutics for diseases where there are no treatment options available. We have performed a large-scale screen that revealed that a host protein, fibrillarin, is essential for infection by Hendra, Nipah and many other paramyxoviruses.  Our study suggests that in the future an antiviral therapy may be developed to combat paramyxovirus infection by modulating fibrillarin activity.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Stewart: Future work will be dedicated to understanding why fibrillarin is so essential for virus infection and exploring whether fibrillarin or related pathways can be blocked for antiviral potential.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Genome-wide siRNA Screening at Biosafety Level 4 Reveals a Crucial Role for Fibrillarin in Henipavirus Infection

Celine Deffrasnes ,Glenn A. Marsh ,Chwan Hong Foo ,Christina L. Rootes ,Cathryn M. Gould ,Julian Grusovin ,Paul Monaghan , Michael K. Lo ,S. Mark Tompkins ,Timothy E. Adams ,John W. Lowenthal ,Kaylene J. Simpson ,Cameron R. Stewart  , Andrew G. D. Bean , Lin-Fa Wang

Published: March 24, 2016

DOI: 10.1371/journal.ppat.1005478

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Dr. Cameron Stewart (2016). Exploiting Pathway in Host Cells May Combat Emerging Viral Infections MedicalResearch.com