A new study reveals a protein that could enable animal viruses to infect humans, marking a significant step towards pre-pandemic preparedness and understanding viral infections.
A new study has unveiled a crucial protein that could bridge the gap between animal viruses and human infections, potentially enabling the spillover of arteriviruses. This discovery adds a new layer of understanding to the mechanisms of viral infections and provides a stepping stone for pre-pandemic preparedness.
Researchers led by The Ohio State University and the University of Wisconsin-Madison have pinpointed a protein in mammals that facilitates the entry of arteriviruses into host cells. Astonishingly, an existing monoclonal antibody targeting this protein has shown promise in protecting cells from infection.
Arteriviruses are a family of viruses that circulate broadly among mammals like nonhuman primates, pigs and horses but remain undetected in humans. While many natural hosts show no signs of illness, some strains can cause severe diseases, such as pneumonia in swine and hemorrhagic fever or encephalitis when switching hosts.
"It's important to consider that since we have no known arteriviruses infecting people that we're essentially immunologically naïve, so we can't rely on preexisting immunity to help us," co-lead author Cody Warren, an assistant professor of veterinary biosciences at The Ohio State University, said in a news release.
Published recently in the journal Nature Communications, the study was co-led by Adam Bailey, assistant professor of pathology and laboratory medicine at the University of Wisconsin-Madison.
The researchers aimed to understand better the infection mechanisms of arteriviruses to gauge human infection risks and prepare for potential spillovers. Using genome-wide CRISPR-knockout screening, Bailey identified two key genes, FCGRT and B2M, whose protein products form the neonatal Fc receptor (FcRn). This receptor is found on immune cells and blood vessel walls -- prime targets for arteriviruses.
Three diverse strains of simian arteriviruses, the porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) and the equine arteritis virus (EAV) were found to use FcRn for entry into host cells. Disrupting the FCGRT gene blocked viral infection, while treating cells with a monoclonal antibody against FcRn provided protection.
"Chimpanzees and humans have pretty much all the same genes, but the sequence of those genes is slightly different. All mammals have the FcRn receptor, but their ability to support infection with a given arterivirus may vary," Bailey said in the news release.
The study also revealed that another surface protein, CD163, plays a role in most arterivirus infections. However, it requires interaction with FcRn to facilitate infection fully.
Spelling out these infection steps marks a significant milestone in virus research.
"If we're looking at virus biology, one of the most important things we can understand is entry mechanisms. Because if you can stop the ability of a virus to infect a cell through disrupting that initial virus-receptor contact, now you have a potential therapeutic strategy," Warren added.
Bailey emphasized the importance of this research for pre-pandemic preparedness.
"If one of these viruses emerged in humans, I believe we'd be in big trouble. So that is the motivator for me," he said.