Yellow fever virus (YFV) is a member of
the flavivirus family that also includes Dengue and Zika virus. The virus,
which is thought to infect a variety of cell types in the body, causes up to
200,000 cases of yellow fever every year, despite the widespread use of a
highly effective vaccine. The vaccine consists of a live, attenuated form of
the virus called YFV-17D, whose RNA genome is more than 99 percent identical to
the virulent strain. This one percent difference in the attenuated virus'
genome may subtly alter interactions with the host immune system so that it
induces a protective immune response without causing disease.
To explore how
viruses interact with their hosts,
and how these processes lead to virulence and disease, Alexander Ploss,
assistant professor of molecular biology, and colleagues at Princeton
University adapted a technique -- called RNA Prime flow -- that can detect RNA
molecules within individual cells. They used the technique to track the
presence of replicating viral particles in various immune cells circulating in
the blood of infected mice. Mice are usually resistant to YFV, but Ploss and
colleagues found that even the attenuated YFV-17D strain was lethal if the
transcription factor STAT1, part of the antiviral interferon signaling pathway,
was removed from mouse immune cells. The finding suggests that interferon
signaling within immune cells protects mice from YFV, and that species-specific
differences in this pathway allow the virus to replicate in humans and certain
other primates but not mice.
The next step, said Florian Douam, a
postdoctoral research associate in the Department of Molecular Biology and
first author on the study, is to confirm YFV replication in these subsets of
immune cells in YFV-infected patients and in recipients of the YFV-17D vaccine.
Viral RNA flow now provides the means to perform such analyses.
To find out more see:
Florian Douam, Gabriela Hrebikova,
Yentli E. Soto Albrecht, Julie Sellau, Yael Sharon, Qiang Ding, Alexander
Ploss. Single-cell
tracking of flavivirus RNA uncovers species-specific interactions with the
immune system dictating disease outcome. Nature Communications, 2017;
8: 14781 DOI: 10.1038/NCOMMS14781
Posted by Dr. Tim Sandle
No comments:
Post a Comment
Pharmaceutical Microbiology Resources