INVESTIGADORES
GARCIA Cybele Carina
congresos y reuniones científicas
Título:
Antiviral effect of the cellular promyelocytic leukemia protein against dengue and Junín RNA viruses
Autor/es:
C. C. GARCÍA; GIOVANNONI, F; CARRO, AC; DAMONTE E.B.
Lugar:
Minneapolis
Reunión:
Congreso; 30th Annual Meeting, American Society for Virology; 2011
Institución organizadora:
ASV
Resumen:
Promyelocytic leukemia (PML) nuclear bodies (NBs)
are discrete nuclear
foci that contain several cellular proteins involved in diverse
processes such as transcription, chromatin structure, DNA repair,
apoptosis and antiviral
responses against a number of viruses. Accumulating reports have revealed
various strategies developed by DNA viruses to disrupt PML NBs. However, very
little information is available about how RNA viruses affect PML NBs. Here
we investigated the antiviral role of PML in the replication of two hemorrhagic
fever causing RNA viruses of great importance in public health, dengue (DENV) and
Junin (JUNV) viruses.
To evaluate the effect of PML on infectious
DENV and JUNV production, A549 cells were transfected with PML-siRNA, and 24 h
later cultures were infected with the respective virus at a MOI of 0.1.
Supernatants were collected at 24 h p.i. and titrated by plaque assay. Results
showed that PML silencing rendered A549 cells more susceptible to both RNA
viruses. The virus yields observed were 90 and 70 % higher for DENV and JUNV,
respectively, in comparison with virus yields obtained in non-transfected cells.
Moreover, confocal images of infected cells have shown that nuclear PML
underwent a dramatic rearrangement during DENV infection becoming more distinct,
with increased numbers and size of PML NBs. On the other hand, the effect observed in JUNV
infected cells was different and included the disruption of PML NBs, surrounded
by diffuse fluorescence in the vicinity of the original structure,
suggesting a marked efflux of PML protein from the nucleus to the
cytoplasm, in comparison with uninfected cells. Different RNA viruses
differ much in their abilities to induce IFN.
Our results suggest that the differential antiviral effect of PML on DENV and
JUNV viruses depends on the specific role of PML in mediating an IFN-induced
antiviral state and also suggests but does not prove that PML NBs structures
have any role in the establishment of persistence arenavirus infection.
In conclusion, this is the first brief report
of the variable susceptibility of RNA viruses
to human PML
proteins. The exact mechanism behind PML-mediated
intracellular defense against DENV and JUNV,
and the strategy by which these viruses evade
this cellular defense mechanism requires further study.