How gastro-causing virus latches onto and infects cells


It's the most common viral cause of diarrhoea worldwide, but norovirus is notoriously tough to study. Scientists in the US used a mouse version of the disease to uncover how it gets into cells. Belinda Smith reports.


Cramps, nausea ... quick, get to a toilet!
Jan-Otto / Getty Images

The dreaded gastro: it sweeps through workplaces, schools, restaurants, resorts – anywhere with loads of people. And while cramps, diarrhoea, vomiting and a general feeling of malaise usually last just a couple of days, how the bug infects people and causes disease is still largely a mystery.

Now, biologists in the US have found a clue. They uncovered the pathogen’s gateway in mice – a protein hanging off the outside of cells to which the virus can latch and sneak inside to replicate. Without the protein, called CD300lf, the virus is unable to invade the cells.

The team presented their work, which could be the first step in the long path to treatments or a vaccine, in Science.

Around 20 million people in the US are struck by acute gastroenteritis each year, leading to 400,000 emergency department visits and hundreds of deaths – mainly among young children and the elderly – all thanks to norovirus, a tiny virus behind 90% of non-bacterial gastroenteritis.

The disease can be severe, or even fatal, in patients already hospitalised or in a nursing home. This isn't helped by the fact that the illness is extremely contagious – even swallowing virus particles in the air after an infected person has vomited is enough to bring someone down with the disease.

But unravelling the cellular mechanisms behind the disease’s virulence has been hampered by the fact that norovirus is really hard to grow in the lab.

While it’ll happily infect and spread through people in real life, it turns its nose up at human cells in a petri dish.

And strains of norovirus are particular to their host species. Scientists can’t infect a mouse or rat with human norovirus. (If you find yourself struck down with norovirus, for instance, it won’t spread to your pets – just other people with whom you come in contact.)

So when, in 2003, a mouse version of norovirus was discovered by scientists at the Washington University in the US, biologists finally had an animal model to study the disease.

Under the microscope, mouse and human norovirus look similar – spherical protein shell around 30 nanometres wide encasing genetic material.

Herbert Virgin, part of the team that found the mouse norovirus as well as the current study, along with Robert Orchard and Craig Wilen, also the Washington University, wanted to find out why the mouse norovirus targeted only mice – and this, perhaps, could point to how the human version infects us.

Using a gene-editing technique called CRISPR-Cas9, they looked for mouse genes that enable norovirus infection by snipping them out and seeing what happened.

They found mouse cells lacking the gene CD300lf were immune to the disease. CD300lf codes for CD300lf, a protein that sits on the surface of mouse cells and Orchard, Wilen and their colleagues believed it key to norovirus infection.

When they inserted the CD300lf gene into the DNA of human cells in a dish, which then began expressing the CD300lf protein, the mouse norovirus had no issue infecting and multiplying inside them too.

"This tells us that the species restriction is due to the ability to get inside the cells in the first place,” Virgin says.

“Once inside the cells, most likely all the other mechanisms are conserved between human and mouse noroviruses since the viruses are so similar."

Strangely, the norovirus needed another molecule – or “co-factor” – to infect cells, but the team was unable to establish its identity.

Orchard thinks it’s probably not a protein, but a small molecule found in blood.

This mystery molecule may be crucial to cajoling the virus to grow in human cells in the lab – and one day, let scientists develop drugs that disrupt the disease's infection route.

  1. http://science.sciencemag.org/lookup/doi/10.1126/science.aaf9286
  2. http://www.cdc.gov/norovirus/trends-outbreaks.html
  3. http://science.sciencemag.org/content/299/5612/1575
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