Scientists find how Rift Valley fever virus enters cells

Overview

• Post By :


• Source: Washington University School of Medicine


• Date: 24 Sep,2021

Rift Valley fever virus causes economically tragic hemorrhagic outbreaks in livestock, including cattle, goats, and sheep. The mosquito-borne infections can lead to the spread of infection to people who work with animals that are dying or dead often causing many human infections as well as many deaths.

Rift Valley fever, for which there isn’t a particular treatment, is restricted to Africa as well as it’s Arabian Peninsula. But mosquitoes that transmit the virus are found throughout the world which means that it is necessary to be aware and manage the virus.

Researchers from the Washington University School of Medicine in St. Louis and the University of Pittsburgh Center for Vaccine Research and School of Public Health discovered that the virus is able to enter cells by making use of the protein that’s which is normally involved in the process of taking up low-density lipoproteins (LDL which are carriers of the so-called bad cholesterol) from blood. The study, which was published on in the journal Cell, on Sept. 23rd in Cell may result in treatments that can help to prevent Rift Valley fever or reduce the severity of it by affecting its ability to enter into cells.

For people in areas where Rift Valley fever is endemic, an outbreak threatens not only their livelihood but their health. People have a 1% to 2% chance of death if they get infected with this virus, which doesn’t sound like much, but it’s about the same as COVID-19. The disease is much more severe in domesticated animals, especially young animals, which get very ill and die in large numbers. This virus has been flying under the radar, but given that it’s transmitted by mosquitoes that are found everywhere, it could spread into other parts of the world and become a serious issue.”

Gaya K. Amarasinghe, PhD, co-senior author, professor of pathology & immunology and of biochemistry & molecular biophysics, Washington University

The World Health Organization has listed Rift Valley fever as a prioritised disease that is likely to create epidemics in the coming years. The virus is easily spread among domestic animals through mosquito bites. Also, people can get infected through mosquito bites, however most people who contract the virus are exposed to animal fluids when they take care of animal suffering from illness or discard their bodies.

To understand how the virus infects cells, the author, Safder Ganaie, PhD an assistant professor who collaborates with Amarasinghe. They cultivated the virus on mice inside a dish. By disrupting the regular mouse gene expression, Ganaie and his colleagues discovered that the virus was not able to infect mice which were deficient in certain genes specifically the gene for LDL-receptor-related protein ( Lrp1). Further tests revealed that the virus requires LRP1 to infect mouse, hamster monkey, cow and human cells. This suggests that the virus is using the same protein in the distantly connected species.

The discovery is an opportunity. If the virus requires LRP1 to be able to infect cells the temporary eliminating LRP1 out of the equation could hinder its be spread throughout the body, thus reducing the chance of developing. The researchers utilized the protein to accomplish this. It is called RAP. The protein is attached to LRP1 and blocks anything else that attempts to attach.

Researchers infected a set of mouse with the virus. They also treating them with RAP. Another mouse group was affected but not treated for comparison. The majority of mice treated did not die, while the mice that were not treated died. Furthermore, the mice that were treated had less virus in their bodies the third day after the infection as compared to mice who were not treated.

RAP isn’t an excellent candidate for development of drugs, because it’s a mammalian normal protein that plays an important role in numerous vital biological processes. However, the findings suggest that targetting LRP1 could lead to treatments that treat Rift Valley fever.

“This discovery is the key to understanding the mechanism by which Rift Valley fever virus spreads not just through the human body, but the ways it can infect mosquitoes as well as other kinds of mammal species. Understanding how the virus is spread can help us develop specific treatments that are currently not available in the case of Rift Valley fever,” said co-author Amy Hartman, PhD, an associate professor of infectious diseases and microbiology in the University of Pittsburgh. “This discovery will open up new possibilities to study viral-host interactions at the cell and organismal levels and improves knowledge of fundamental nature of emerging mosquito-transmitted viruses.”

The finding of the fact that Rift Valley fever utilizes LRP1 to enter cells is intriguing since the protein is recognized for its function in the process of metabolizing cholesterol. It’s also thought to be involved in Alzheimer’s and in the intestinal bacteria C. difficile. It’s unclear why these biological processes that are not related but Amarasinghe, Hartman and their colleagues have a number of initiatives underway to study the connections.