Scientists from the lab of Biochemistry and Molecular Genetics Prof. Edward H. Egelman, Ph.D., have found a novel interaction between the protein capsule and DNA of the SIRV2 virus that allows the virus to survive when moving from cell to cell within populations of Sulfolobus islandicus, a bacterial species that live in conditions such as boiling acid.
Resistance to external stress is a feature found in various organisms that produce spores. Examples of spore forming bacteria include clostridium difficile, responsible for approximately 30,000 deaths per year often in hospitals and nursing homes, and anthrax, a biological weapon that can be ground and delivered covertly in envelopes, Egelman said.
Egelman was able to connect the SIRV2 resistance to resistance found in spores. The important structure is A-form DNA.
“Back in 1951, Rosalind Franklin described two forms of DNA,” Egelman said “One was dehydrated [A-form] and the other was in a human environment [B-form], and the irony is that many people thought in the 65 years since then that the A-form is an in vitro artifact because DNA never occurs in a desiccated state in biology.”
However, A-form DNA, far from being an artificial lab product, is the thread that links the resistance to harsh conditions found in bacterial spores or SIRV2.
“Bacterial spores transition between A-form and B-form DNA in vivo and we made the connection that this seems to be a possible universal strategy of viruses that thrive in very very harsh environments and bacterial spores,” Egelman said.
While A-form DNA exists in solution-rich biological systems, the relation between A-form DNA and desiccation is maintained. “Biochemistry, fifth edition” by Berg, Stryer and Tymoczko describes different ribose sugar ring puckering and different positions of the major and minor grooves in A-form DNA. These structural changes are designed to exclude water from A-form DNA even in biological systems.
Therefore, the SIRV2 virus has its own mechanism, based on its protein capsule, of excluding water from DNA to induce the A-form.
Egelman said the interesting aspect of this protein is that it unfolds in solution. Only when the protein associates with the DNA of the virus, does it fold. It is this folding and association of the protein with the viral DNA that induces A-form DNA.
“What we showed in this virus is that the wrapping of protein around the DNA is actually so tight that every water molecule is excluded so that DNA is essentially being dried by the protein,” Egelman said.
Egelman added that this finding has led to further questions about the molecular biology of the SIRV2 virus, especially relating to how the protected A-form DNA reverts to a form of DNA that can undergo replication and transcription to form viral progeny when the virus infects a host cell.
“We’d like to know many things in terms of how the virus assembles with the host cell,” Egelman said. “Once this virus infects another Sulfolobus islandicus bacterium, how does the DNA get released as the DNA is still encapsulated?”
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