Rodent-borne pathogens like hantaviruses and arenaviruses are simple, but resourceful, and very successful at propagating. Due to a tiny genome generating a mere four proteins compared to humans' thousands, they rely on human biological machinery to do their replication dirty work, facilitating infection, plus a high mortality rate. Vermont researchers have discovered a mechanism that when targeted, may stop these deadly viruses in their tracks.
A new study published in Cell Host & Microbe by the University of Vermont's Jason Botten, Ph.D., assistant professor of medicine and microbiology and molecular genetics, and graduate student Joseph Klaus and colleagues offers a paradigm shift for scientists' understanding of the functionality of a protein that resides in the cell's secretory pathway and gets "shuttled" from one end of the cell to the other.
Antivirals or vaccines do not exist for these pathogens, so gaining a better understanding of how they replicate was at the heart of Botten and colleagues' investigation.
"The 'catch' with these viruses is that each different species has a tailor-made mouse host, like a deer mouse, white-footed mouse, etc.," explains Botten. In addition, he says, because these viruses and their rodent hosts have co-evolved for millions of years, they do not cause any apparent disease in the mice. "It's a beautiful relationship," he remarks, noting that because these viruses are not dependent on humans for their maintenance in nature, when humans do get infected, they get very sick.
The team closely examined the interaction between the virus proteins and the host proteins, a process that yielded the creation of a map the first ever of human protein partners of arenavirus and hantavirus glycoproteins (GPs). "The mapping allowed all kinds of analysis regarding which pathways of human cells the virus is tapping into," says Botten.
GPs reside on the surface of the virus and allow i
|Contact: Jennifer Nachbur|
University of Vermont