With Covid-19 cases increasing across the world, researchers are working to better understand how the virus that causes the disease infects cells and spreads through the body.
Many viruses—including Dengue, hepatitis C, and West Nile—exit through the biosynthetic secretory pathway. It is the central pathway that cells utilized to transport hormones, growth factors, and other materials to their surrounding environment.
A team led by Drs. Nihal Altan-Bonnet and Sourish Ghosh at National Institutes of Health’s (NIH) National Heart, Lung, and Blood Institute (NHLBI) and Dr. Gregoire Altan-Bonnet at NIH’s National Cancer Institute (NCI) investigated whether coronaviruses also utilize this pathway to exit cells.
They used a related coronavirus called MHV as well as SARS-COV-2 for their experiments. Funded by several NIH Institutes, the study was published recently in Cell.
The scientists chemically blocked the biosynthetic secretory pathway in MHV-infected cells. Using microscopic imaging and virus-specific markers, they discovered that the viruses still left cells with this pathway blocked.
Further experiments revealed that the viruses instead exited infected cells through the lysosome, an organelle that serves as the cells’ trash disposal system. Normally, the lysosome’s acidic environment helps destroy viruses and other pathogens before leaving cells. SARS-CoV-2 was also found in the lysosomes of infected cells.
Researchers discovered that lysosomes were de-acidified in coronavirus-infected cells. This significantly weakened the activity of their destructive enzymes. As a result, the coronaviruses remained intact and ready to infect other cells when they exited.
Dr. Nihal Altan-Bonnet says, “These coronaviruses are very sneaky. They’re using these lysosomes to get out, but they’re also disrupting the lysosome so it can’t do its job or function.”
With this mechanism being identified, researchers may be able to find ways to disrupt the pathway. The authors identified one experimental compound that potently blocked coronaviruses from getting out of cells.
But more studies are needed to determine whether this drug or others that block the lysosome pathway could be used to combat Covid-19.
Some immune system cells rely on lysosomes to degrade proteins into short pieces that help trigger other immune cells to respond. Scientists found that the coronavirus deactivated this disease-fighting function of the lysosome. De-acidification of the lysosome may alter other immune system functions as well. The findings could help explain some of the immune system abnormalities seen with Covid-19 patients.
(With inputs from The OnLook News Research Bureau)