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Catching A Virus With The Help Of Its Tail

Some RNA viruses insert their genetic material as one piece, while others cut it into pieces. The latter are appropriately called segmented viruses.

Such segmented RNA viruses causing human diseases like influenza, have been a long-standing puzzle for researchers: how do they achieve accurate copy and insertion of each segment? How do they ensure that all individual segments are copied by the same enzyme and at the same time ensure that each segment can produce different amounts of RNA? Such exquisite regulation is essential to make the correct levels of viral proteins necessary for successful replication.

Now, research by scientists at the Blavatnik Institute at the Harvard Medical School yields a surprising answer: the viral machinery in charge of this survival maneuver is activated by an RNA from the opposite end of the segment where the copy begins.

The findings, published on May 9 in PNAS, identify new potential targets to inhibit the replication of segmented viruses. This group comprises various emerging and highly fatal viruses, like Lassa fever virus, bunyaviruses like La Crosse and Rift Valley fever, as well as the most common and well-known influenza viruses.

"Change in climate has modified and intensified the spread of some severe and emerging viruses to new geographic regions, making a serious challenge to global health," said Sean, "Our findings identify a complex mechanism allowing some of these pathogens to replicate and survive." PJ Whelan, professor of microbiology at HMS and director of the Harvard Program in Virology.

Lassa fever infections, for example, are rarely fatal, but once a real disease develops, it can cause bleeding or bleeding in multiple organs in one in five people. The death rate can reach 50 percent during epidemics, according to the Centers for Disease Control and Prevention.

In the study, Whelan and study co-author Jesse Pyle, a graduate student in Whelan's lab, worked with the Machupo virus, an arenavirus, which, like the Lassa virus, infects rodents which in turn transmit the virus to human beings where it causes fatal hemorrhagic fevers.

Unlike the influenza virus, whose genome has eight segments, the Machupo virus has only two segments, called small and large segments, that offer a much simpler way to understand how the different segments are copied in the correct amounts.

Previous signs about this mechanism came from research on influenza viruses and La Crosse that showcased that the viral protein responsible for copying the key segment, the RNA-dependent RNA polymerase (RdRP), interacts with the 5 'end of the segment, which is the exact opposite end to the location where the protein initiates the copy. However, the importance of this interaction was not fully understood.

By: Preeti Narula