Researchers still know very little about just how norovirus works, but a new study has shed light on how norovirus gets into cells and causes disease.
According to the Centers for Disease Control and Prevention (CDC), norovirus causes about 20 million cases of acute gastroenteritis each year in the United States, along with more than 400,000 emergency room visits and 570 to 800 deaths. Researchers still know very little about just how norovirus works, but a new study has shed light on how norovirus gets into cells and causes disease.
What we do know about norovirus is that it’s a virulent and highly infectious virus, familiar to most as “the stomach bug.” It affects the stomach and intestines, causing cramping, diarrhea, or vomiting. In people who are healthy, a norovirus illness usually passes quickly. For children, the elderly, and people who are medically vulnerable, these infections can be more severe and prolonged, and these groups are the ones that make up most norovirus-related deaths. The main sources of norovirus are through consumption of contaminated food or water, contact with an infected person, or contact with a surface that’s been exposed to the virus. People with norovirus can spread symptoms during infection as well as after symptoms have passed, through contact with feces and vomit.
This new study published in the journal Science included authors from Washington University School of Medicine in St. Louis, Missouri and the Broad Institute of MIT and Harvard in Cambridge, Massachusetts. Their objective was to identify the host factors required for norovirus infection. Though there are many strains of norovirus, they’ve been found to each infect only one species. This makes studying the virus in a laboratory setting difficult, as the strains affecting humans do not infect the mice or rats often used in medical testing. Likewise, researchers have not been able to grow norovirus in human cells in their labs. For this study, the researchers studied mice infected with a strain of mouse norovirus, which has a very similar genome to human norovirus.
The researchers hoped they could model a norovirus infection, and used the CRISPR-Cas9 to identify mouse genes that are important for mouse noroviral infection. They found host molecules essential to causing cell death in norovirus in mice, including one proteinaceous receptor known as CD300lf. This receptor is essential for binding and replication of norovirus in cell lines and primary cells of mice. In their research, the team also found that Cd300lf−/− mice are resistant to norovirus infection.
When the researchers used the CRISPR-Cas9 to eliminate the CD300lf gene, the norovirus could not infect the cells. They also found that expression of CD300lf in human cells breaks the species barrier that would otherwise restrict mouse norovirus from replicating in human cells, and were able to get the mouse virus to infect and multiply in human cells by expressing the CD300lf protein to human cells. A second co-factor in mouse norovirus was detected but remained unidentified in this study.
This research will likely yield new studies on noroviral infections, as identifying the receptor CD300lf in mice is a huge discovery in such an unknown virus. Until more is known about norovirus, preventing infection remains key to stopping its spread.
The CDC recommends the following safety measures against the virus: