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BLOOMINGTON, Ind.—Biologists have known for years that viruses spread by infecting new cells, but a recent study by researchers from Indiana University and Montana State University has indicated that the infection of the cells might be more specific. The researchers' work discovered that viruses 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 proteins in order to escape from infected cells. The group that these viruses hijack in both eukaryotes (plants and animals) and archaea are called the endosomal sorting complexes required for transport (ESCRT). Scientists have dated archaea back to 3.7 billion years, with the oldest fossils of eukaryotes dating back to 1.7 billion years.
The work began with the study of Sulfolobus turreted icosahedral 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 as HIV and Ebola, STIV has a similar dependence on its host's ESCRT proteins to complete its life cycle.
Through two-hybrid screening, which identifies interactions between two proteins or a protein and a DNA molecule, researchers discovered two examples where viral proteins—the major capsid protein B345 and the viral protein C92—interacted with ESCRT proteins—SSO0619 and SSO0910. Epifluorescence microscopy revealed spots of the ESCRT protein Vps4 in STIV-infected S. solfataricus cells, though no Vps4 was found in uninfected cells. Further testing with transmission electron microscopy led to the discovery that Vps4 was localized in seven-sided pyramid-like structures (viral budding sites) that form in the membrane of S. solfataricus before viruses cause cell breakdown when the viral protein C92 is expressed. In contrast, no localization of Vps4 was seen in similar cells in which C92 is repressed.
"We believe the ESCRT machinery plays two roles in STIV biology. First, by virtue of interaction between the viral B345 protein and the host protein SSO0619, ESCRT aids in the construction of the STIV viral particles," said Stephen D. Bell, professor in the IU Department of Molecular and Cellular Biochemistry and Department of Biology. "Second, the strong association we find between the pyramid structures formed by C92 and ESCRT's Vps4 protein allows us to hypothesize that the ESCRT machinery plays a vital role in opening those pyramid exit structures that then leads to cell disruption and the release of viral progeny."
In the S. solfataricus thermophile, Vps4 is recruited to viral budding sites. Similarly, other researchers have shown that the Vps4 protein of the eukaryotic ESCRT machinery localizes to the HIV budding site in humans.
The study has shown that the ESCRT machinery plays an equally pivotal role in cell division for both eukaryotic organisms and microorganisms such as archaea, and as such is hijacked by viruses in both groups.
"The new work yields insight into the evolution of the relationship between hosts and viruses and, more importantly, presents us with a new and simple model 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 of Sciences on June 10. Bell and Mark J. Young of Montana State University were co-lead authors, with Jamie C. Snyder and Susan K. Brumfield of Montana State University and Rachel Y. Samson of Indiana University co-authoring. The research was funded by the National Science Foundation, the National Aeronautics and Space Administration, the Wellcome Trust and the IU College of Arts and Sciences.