INVESTIGADORES
TRONO Karina Gabriela
artículos
Título:
The bovine leukemia virus microRNAs permit escape from innate immune response and contribute to viral replication in the natural host
Autor/es:
GILLET NICOLAS; MALIK HAMAIDIA; DE BROGNIEZ ALIX; GERONIMO GUTIERREZ; RENOTTE NATHALIE; REICHERT MICHAL; KARINA TRONO; WILLEMS LUC
Revista:
RETROVIROLOGY
Editorial:
BIOMED CENTRAL LTD
Referencias:
Lugar: Londres; Año: 2015 vol. 12 p. 9 - 9
ISSN:
1742-4690
Resumen:
In the natural host (Bos taurus), infection with bovine leukemia
virus (BLV) remains mostly asymptomatic, resulting
in a benign lymphocytosis only in about one-third of
infected animals and even less frequently in a B-cell leukemia/
lymphoma (10% of cases). BLV can also be experimentally
transmitted to sheep that almost invariably
develop leukemia/lymphoma after shorter latency periods.
Upon integration, the BLV provirus becomes transcriptionally
silent except for the microRNAs that remain very
abundantly expressed. We used reverse genetics to evaluate
the role of the viral microRNAs in the natural and
experimental hosts. A BLV lacking the microRNAs replicated
at wild-type levels in sheep, indicating that these
sequences were dispensable. Surprisingly, the microRNAs
were required for efficient replication in cows, thereby
underlining the importance of studying viral determinants
in the natural host. To understand the mechanisms associated
with the microRNAs, we performed high-throughput
RNA-sequencing of transgenic B cell lines and
peripheral blood mononuclear cells isolated from cows
infected either by wild-type or by isogenic microRNAdeleted
viruses. Bioinformatic analyses revealed that BLV
microRNAs modulate a series of pathways that include
B-cell signaling and immunity. Reporter assays showed
that the microRNAs target granzyme A and c-FOS transcripts
and downregulate indirectly Annexin A1 and phosphoinositide-
3-kinase PIK3CG. Finally, expression of the
microRNAs in B-lymphocytes was associated with a
decrease in phagocytosis by primary bovine macrophages.