New model that could revolutionize the treatment of brain inflammation from RVFV

The first mouse model that faithfully mimics the brain damage caused by severe RVFV infection will allow the study of disease mechanisms in detail and provide an opportunity to conduct high-throughput preclinical testing of next-generation drugs, which are therapies for the viruses that exist. will enable the development of across Africa.

According to senior author Anita McElroy, MD, PhD, virologist and pediatric infectious disease physician at the Pitts School of Medicine and UPMC Children’s Hospital of Pittsburgh, Rift Valley fever can spread to villages with devastating consequences, but no drugs or vaccines. what we can give to the people.

He further noted that before IV acyclovir became available in the 1990s, the outcome of herpes simplex virus encephalitis in newborns was dire. But acyclovir turned that trend on its heels, and the same success can be seen with RVFV encephalitis, she said.

According to virologists, a virus that mosquitoes transmit between animals and people, RVFV is endemic to the African continent and belongs to a family of viruses identified by the National Allergy and Infectious Diseases (NIAID) working group on pandemic preparedness. could work. increase for future pandemics.

The study, published today in PLOS Pathogens, says that unlike other mosquito-borne infectious diseases such as malaria, RVFV can be spread by multiple species of mosquitoes, extending their ability to sweep great distances and reach multiple hosts. Some blood sample surveys suggest that by adulthood, up to 50% of Africans living in endemic areas have been exposed to the virus in their lifetime.

Even though the overall mortality rate of RVFV infection is relatively low, estimated at between 1% and 3%, the virus causes major economic and public health impacts across Africa, it said.

RVFV is spread by infected animals, especially livestock mosquitoes, which eventually find their way into people. Farmers and butchers are particularly vulnerable to infection because the virus can be spread through bodily fluids in mucous membranes and also through cuts and abrasions in the skin.

Once the virus infects a human, it can spread to the liver and brain and cause hepatitis, encephalitis, or both. Nevertheless, despite the economic and human toll of the virus, a vaccine for RVFV has not been made commercially available, and efforts to develop an effective therapy have historically been hindered by the lack of a suitable preclinical model. .

Unlike humans, whose genetic diversity likely explains why some develop mild disease and some die of liver failure or brain damage, normal strains of RVFV-injected mice die of liver disease.

McElroy and colleagues sought to address this challenge by testing mice with different genetic backgrounds and measuring their susceptibility to RVFV infection by identifying a genetically diverse but stable mouse model and mapping the genetic differences that lead to RVFV infection. These determine how the infection presents itself in the body.

One strain, labeled CC057/Unc, developed persistent late-onset encephalitis and had a high viral load in the brain without developing severe acute hepatitis, making it particularly suitable for studying the neurological form of RVFV disease. became suitable.

Noting that it is impossible to study how RVFV causes brain disease if animals die of liver failure, McElroy said the new model is an important step forward in finding out why some people who get the virus and others die and how can they be helped in the best possible way.

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