Flaviviruses (FVs) represent a family of viral pathogens
responsible for human life-threatening diseases such as Dengue Fever, West
Nile, Yellow Fever and Japanese Encephalitis.
The infectious agent within this family of viruses is single-stranded
RNA. During the process of infection
(through arthropod vectors), the viral genome (gRNA) is successfully replicated
and subgenomic flaviviral RNAs (sfRNAs) are also produced. In animal studies, it has been demonstrated
that these sfRNAs are an integral part of the disease process. It is interesting to note that these sfRNAs
are produced as a result of the incomplete degradation of gRNA by the host-derived
exonuclease Xm1 – an enzyme that is a part of the host cell defense against
infection. In this scenario, host cell
defenses inadvertently play a crucial role in producing disease.
This resistance to complete degradation of gRNA by Xm1 has
been shown to be due to specific RNA sequences that are referred to as
Xm1-resistant RNAs (xrRNAs). It is
therefore of interest to more fully understand the molecular structure of xrRNAs and,
therefore, elucidate the nature of the resistance to the action of Xm1.
Dr. Erich G. Chapman and his colleagues at the Department of
Biochemistry and Molecular Genetics, School of Medicine, University of Colorado
at Denver focused their research efforts on establishing the unique and precise
structural aspects of xrRNAs that make
them impervious to Xm1-mediated
degradation.
As a result of their extensive analysis they were able to show
that the three-dimensional structure of xrRNAs consist of a “ringlike”
conformation that prevents Xm1 from breaking down sfRNAs. In addition, the investigators purposefully
disrupted this structure and effectively prevented the formation of sfRNAs
during infection. This is an important finding; for, it helps clarify the mechanism of FV infections that impact many individuals throughout the world.
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