Going viral

Researchers discover that viruses for both microorganisms and humans commandeer the ESCRT proteins in order to spread

Kelsey Kaustinen
BLOOMINGTON, Ind.—Biologists have known for years thatviruses spread by infecting new cells, but a recent study by researchers fromIndiana University and Montana State University has indicated that theinfection of the cells might be more specific. The researchers' work discovered thatviruses such as HIV and Ebola, and viruses that infect organisms known as archaea(which grow in volcanic hot springs), both commandeer a certain set of proteinsin order to escape from infected cells. The group that these viruses hijack inboth eukaryotes (plants and animals) and archaea are called the endosomal sorting complexes required for transport (ESCRT). Scientists have dated archaeaback to 3.7 billion years, with the oldest fossils of eukaryotes dating back to1.7 billion years.
 
 
The work began with the study of Sulfolobus turretedicosahedral virus (STIV), a virus that infects Sulfolobus solfataricus, a species of archaea called a thermophile.The researchers discovered that, similar to viruses that infect people, such asHIV and Ebola, STIV has a similar dependence on its host's ESCRT proteins tocomplete its life cycle.
 
 
Through two-hybrid screening, which identifies interactionsbetween two proteins or a protein and a DNA molecule, researchers discoveredtwo examples where viral proteins—the major capsid protein B345 and the viralprotein C92—interacted with ESCRT proteins—SSO0619 and SSO0910. Epifluorescencemicroscopy revealed spots of the ESCRT protein Vps4 in STIV-infected S. solfataricus cells, though no Vps4was found in uninfected cells. Further testing with transmission electronmicroscopy led to the discovery that Vps4 was localized in seven-sidedpyramid-like structures (viral budding sites) that form in the membrane of S. solfataricus before viruses causecell breakdown when the viral protein C92 is expressed. In contrast, nolocalization of Vps4 was seen in similar cells in which C92 is repressed.
 
 
"We believe the ESCRT machinery plays two roles in STIVbiology. First, by virtue of interaction between the viral B345 protein and thehost protein SSO0619, ESCRT aids in the construction of the STIV viralparticles," said Stephen D. Bell, professor in the IU Department of Molecularand Cellular Biochemistry and Department of Biology. "Second, the strongassociation we find between the pyramid structures formed by C92 and ESCRT'sVps4 protein allows us to hypothesize that the ESCRT machinery plays a vitalrole in opening those pyramid exit structures that then leads to celldisruption and the release of viral progeny."
 
 
In the S. solfataricusthermophile, Vps4 is recruited to viral budding sites. Similarly, other researchershave shown that the Vps4 protein of the eukaryotic ESCRT machinery localizes tothe HIV budding site in humans.
 
 
The study has shown that the ESCRT machinery plays anequally pivotal role in cell division for both eukaryotic organisms andmicroorganisms such as archaea, and as such is hijacked by viruses in bothgroups.

"The new work yields insight into the evolution of the relationship betweenhosts and viruses and, more importantly, presents us with a new and simplemodel system to study how viruses can hijack and utilize cellular machineries,"noted Bell, co-lead author on the study. 
 
The paper appeared in early online editions of the Proceedings of the National Academy ofSciences on June 10. Bell and Mark J. Young of Montana State University wereco-lead authors, with Jamie C. Snyder and Susan K. Brumfield of Montana StateUniversity and Rachel Y. Samson of Indiana University co-authoring. Theresearch was funded by the National Science Foundation, the NationalAeronautics and Space Administration, the Wellcome Trust and the IU College ofArts and Sciences.
 


Kelsey Kaustinen

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