CLINICAL CASES
21
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Uridine
Ribavarin
Ribavarin
Figure 2-2.
The pseudo base (1,2,4-triazole 3-carboxamide) of ribavirin pairs
equivalently with cytosine and uracil. R denotes the polyribonucleotide strand.
In 2001 a critical study published in
Nature Medicine
showed in vitro use
of ribavirin triphosphate by a model viral RNA polymerase, poliovirus 3D
pol.
Ribavirin incorporation is mutagenic,
because it serves as a
template for
incorporation of cytidine and uridine
with equal efficiency (Figure 2-2).
Ribavirin reduces infectious poliovirus production to as little as 0.00001 percent
in cell culture. The
antiviral activity of ribavirin correlates directly with its
mutagenic activity.
These data indicate that ribavirin forces the virus into
“error catastrophe.” This study reveals a new concept about nucleoside analogs,
that is, mutagenic ribonucleosides may represent an important class of anti-RNA
virus agents.
RNA v
iruses like HIV and the influenza virus use a naturally high
mutation rate
of their RNA polymerases with low fidelity for replication to
avoid and escape most treatments and vaccines. A
RNA virus tends to mis-
takenly insert ribavirin
into newly synthesized copies of their RNA genome.
But ribavirin adds so many extra mutations to the virus during the replication
of its genetic materials, it induces a flood of mutations and thus pushes the
virus into a kind of
genetic meltdown
.
C O M P R E H E N SIO N Q U E ST IO N S
[2.1]
Influenza virus is a class Vb virus, which means that it has a single (-)-
stranded RNA for its genome. Which of the following best describes
the immediate fate of this (-)-RNA when the virus enters the host cell?
A. It is used directly to encode viral proteins.
B. It is used as a template to synthesize a (+)-strand viral messenger
RNA (mRNA).
C. It is used as a template to synthesize viral DNA.
D. It is converted to a provirus.
E. It is integrated into the host cell genome.
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