Actin’ up: Herpesvirus Interactions with Rho GTPase Signaling

Herpesviruses constitute a very large and diverse family of DNA viruses, which can generally be subdivided in alpha-, beta- and gammaherpesvirus subfamilies. Increasing evidence indicates that many herpesviruses interact with cytoskeleton-regulating Rho GTPase signaling pathways during different phases of their replication cycle. Because of the large differences between herpesvirus subfamilies, the molecular mechanisms and specific consequences of individual herpesvirus interactions with Rho GTPase signaling may differ. However, some evolutionary distinct but similar general effects on Rho GTPase signaling and the cytoskeleton have also been reported. Examples of these include Rho GTPase-mediated nuclear translocation of virus during entry in a host cell and Rho GTPase-mediated viral cell-to-cell spread during later stages of infection. The current review gives an overview of both general and individual interactions of herpesviruses with Rho GTPase signaling

High-throughput sequencing reveals novel microRNAs in a retrovirus-induced ovine model of leukemia

info:eu-repo/semantics/publishe

Pseudorabies virus US3 triggers RhoA phosphorylation to reorganize the actin cytoskeleton

The conserved alphaherpesviral serine/threonine kinase US3 causes dramatic changes in the actin cytoskeleton, consisting of actin stress fiber breakdown and protrusion formation, associated with increased viral spread. In this report, we show that US3 expression leads to RhoA phosphorylation at serine 188 (S188), one of the hallmarks of suppressed RhoA signaling, and that expression of a non-phosphorylatable RhoA variant interferes with the ability of US3 to induce actin rearrangements. Furthermore, inhibition of cellular protein kinase A (PKA) abrogates the ability of US3 to induce S188 RhoA phosphorylation, pointing to a role for PKA in US3-induced RhoA phosphorylation. Hence, the US3 kinase leads to PKA-dependent S188 RhoA phosphorylation, which contributes to US3-mediated actin rearrangements. Our data suggest that US3 efficiently usurps the antagonistic RhoA and Cdc42/Rac1/PAK signaling branches to rearrange the actin cytoskeleton

Deep sequencing reveals abundant non-canonical retroviral microRNAs in B-cell leukemia/lymphoma

Viral tumor models have significantly contributed to our understanding of oncogenic mechanisms. How transforming delta-retroviruses induce malignancy however remains poorly understood, especially as viral mRNA/protein are tightly silenced in tumors. Here, using deep sequencing of broad windows of small RNA sizes in the Bovine Leukemia Virus ovine model of leukemia/lymphoma, we provide in vivo evidence of the production of non-canonical Pol IIItranscribed viral microRNAs in leukemic B-cells in the complete absence of Pol II 5’ LTR-driven transcriptional activity. Processed from a cluster of five independent self-sufficient transcriptional units located in a proviral region dispensable for in vivo infectivity, BLV microRNAs represent ~ 40 % of all microRNAs in both experimental and natural malignancy. They are subject to strong purifying selection and associate with Argonautes, consistent with a critical function in silencing of important cellular and/or viral targets. BLV microRNAs are strongly expressed in preleukemic and malignant cells in which structural and regulatory gene expression is repressed, suggesting a key role in tumor onset and progression. Understanding how Pol III-dependent microRNAs subvert cellular and viral pathways will contribute in deciphering the intricate perturbations that underlie malignant transformation