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High-throughput screen under high level containment identifies potential henipavirus drug target

The closely related 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 them, partly because research has to be conducted under extreme level containment conditions.

A study published in PLOS Pathogens reports the first high-throughput RNA interference screen for host genes that are essential for live henipavirus infection of human cells, and identifies a specific cell protein called fibrillarin as a potential target for drugs against henipaviruses and other paramyxoviruses.

Henipaviruses infection is common in bats, and outbreaks in Australia and Malaysia have been linked to human contact with local fruit bats. No human vaccines or treatments exist, and because of high mortality rates (between 35 and 90% of patients known to be infected died in recent outbreaks) the viruses have been classified as biosafety-level 4 (BSL-4) pathogens the highest biosafety containment level. A multi-disciplinary research team led by Cameron Stewart of the CSIRO Australian Animal Health Laboratory in East Geelong, Victoria, systematically interfered with the function of genes in human cells to identify host genes that are needed for henipavirus infection.

In their initial screen, the researchers identified several hundred human genes whose function was necessary for successful henipavirus infection. They subsequently honed in on one of them, called fibrillarin, which codes for a protein present in the nucleolus. The nucleolus is the largest structure in the nucleus of mammalian cells and functions as the assembly room for so-called ribosomes which are subsequently exported out of the nucleus into the cytoplasm and become the protein factories of the cell.

Image of human cells infected with Hendra virus
Infection of human cells with Hendra virus (green) is critically dependent on fibrillarin (red), a host protein that resides deep within the cell nucleus (blue)
Image Credit: Deffrasnes C, Marsh GA, Foo CH, Rootes CL, Gould CM, Grusovin J, et al.(2016)