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  3. Medizin - Open Access LMU - Teil 20/22 Podcast
  4. Degradation of cellular mir-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo.
Cytomegaloviruses express large amounts of viral miRNAs during
lytic infection, yet, they only modestly alter the cellular miRNA
profile. The most prominent alteration upon lytic murine
cytomegalovirus (MCMV) infection is the rapid degradation of the
cellular miR-27a and miR-27b. Here, we report that this regulation
is mediated by the ∼1.7 kb spliced and highly abundant MCMV m169
transcript. Specificity to miR-27a/b is mediated by a single,
apparently optimized, miRNA binding site located in its 3'-UTR.
This site is easily and efficiently retargeted to other cellular
and viral miRNAs by target site replacement. Expression of the
3'-UTR of m169 by an adenoviral vector was sufficient to mediate
its function, indicating that no other viral factors are essential
in this process. Degradation of miR-27a/b was found to be
accompanied by 3'-tailing and -trimming. Despite its dramatic
effect on miRNA stability, we found this interaction to be mutual,
indicating potential regulation of m169 by miR-27a/b. Most
interestingly, three mutant viruses no longer able to target
miR-27a/b, either due to miRNA target site disruption or target
site replacement, showed significant attenuation in multiple organs
as early as 4 days post infection, indicating that degradation of
miR-27a/b is important for efficient MCMV replication in vivo.

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