Apart from being the masterful invaders, viruses cannibalize host cells through injection of their genetic material, often making thousands of copies of themselves in a single cell to ensure their replication and survival.
As for some RNA viruses, they insert their genetic material as a single piece while others chop it up into pieces. Scientists named the latter as segmented viruses.
These segmented RNA viruses such as several that cause human diseases like influenza have been a longstanding enigma to researchers. Some of the critical pain points include how they will accomplish the precise copying and insertion of each segment. Or, how they will ensure that individual segments are all copied by the same enzyme while ensuring that each segment can make different amounts of RNA. This exquisite regulation is crucial to make the correct levels of the viral proteins necessary for successful replication.
At present, research by scientists at Harvard Medical School's Blavatnik Institute yields a surprising answer. The viral workings responsible for this survival-ensuring exercise becomes activated by an RNA from the opposite end of the segment where copying starts.
The team published the results of their study in PNAS that identify new potential targets to inhibit the replication of segmented viruses. Included in this group are several emerging and highly fatal viruses such as Lassa fever virus, bunyaviruses like La Crosse and Rift Valley fever, as well as the better known and more common influenza viruses.
Director of the Harvard Program in Virology and professor of microbiology, Sean P.J. Whelan said that climate change has altered and intensified the spread of some dangerous and emerging viruses to new geographic regions, creating an acute challenge to global health. Their discoveries identify a critical mechanism that allows some of these pathogens to replicate and survive.
Jesse Pyle, co-author of the study, and Whelan ran their research with the Machupo virus, an arenavirus which like Lassa virus infects rodents that in turn transmit the virus to humans where it causes deadly hemorrhagic fevers.
Different from the flu virus whose genome has eight segments, Machupo virus has only two segments - small and large segments - that offer a much simpler way to understand how several segments are copied in the correct amounts.
Currently, antiviral drugs on the market directly target viral enzymes involved in replicating material or in the processing of viral proteins. However, none interfere with the particular mechanism described in the current study.
Whelan explained that their work demonstrates that both the 5' RNA and its binding site on the viral enzyme are potential new targets for inhibition of viral replication. An essential next goal would be to hunt for molecules that interfere with this process and set the stage for new drug design.
