STAT3 activation by KSHV correlates with IL-10, IL-6 and IL-23 release and an autophagic block in dendritic cells

Abstract

Kaposis's sarcoma associated herpesvirus (KSHV) has been reported to infect, among others, monocytes and dendritic cells DCs impairing their function. However, the underlying mechanisms remain not completely elucidated yet. Here we show that DC exposure to active or UV-inactivated KSHV resulted in STAT3 phosphorylation. This effect, partially dependent on KSHV-engagement of DC-SIGN, induced a high release of IL-10, IL-6 and IL-23, cytokines that in turn might maintain STAT3 in a phosphorylated state. STAT3 activation also correlated with a block of autophagy in DCs, as indicated by LC3II reduction and p62 accumulation. The IL-10, IL-6 and IL-23 release and the autophagic block could be overcome by inhibiting STAT3 activation, highlighting the role of STAT3 in mediating such effects. In conclusion, here we show that STAT3 activation can be one of the molecular mechanisms leading to KSHV-mediated DC dysfunction, that might allow viral persistence and the onset of KSHV-associated malignancies.

Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases

“…The requirement for IL-6 during KSHV infection is well documented [30][31][32][33][34][35][36][37][38], but the role of GADD45B may be more nuanced. While we demonstrated that it escapes host shutoff during lytic KSHV infection and appears important for viral reactivation in the iSLK.219 model, GADD45B expression is repressed by viral miRNAs during latency to avoid its cell cycle arrest and pro-apoptotic functions [73].…”

“…IL-6 expression is required for survival of B cells infected with KSHV, and the virus engages a number of strategies to drive production of this cytokine [30][31][32][33][34][35][36][37][38]. The IL-6 mRNA is directly refractory to SOX cleavage and thus remains robustly induced during host shutoff due to the presence of a specific 'SOX resistance element' (SRE) [26,29].…”

Epstein-Barr Virus Blocks the Autophagic Flux and Appropriates the Autophagic Machinery To Enhance Viral Replication

“…In particular, the KSHV immediate-early gene ORF50, expressed during KSHV replication, is responsible for autophagy induction. On the other hand, KSHV, during its latent infection, blocks autophagy in dendritic cells to escape from their immune control (16,17). It also has been reported that the KSHV-encoded protein vFLIP induces an autophagic block in NIH 3T3 cells as well as in the naturally KSHVinfected BCBL1 cells (18).…”

Multimode Microsensors Based on Carbon Matrices Used for the Assay of IL-6 in Whole Blood Samples

“…Garanty-Bogakca and coworkers determined the effect of weight loss in response to a lifestyle modification on the serum levels of inflammatory markers in obese children and adolescents. 7 IL-6 levels in serum were measured to date using the classical method enzyme-linked immunosorbent assay (ELISA), [8][9][10] but this method encounters difficulties, such as time consuming analysis, expensive reagents and only monoclonal antibodies can be used as matched pairs.Multimode sensors is a concept developed by the group of Stefanvan Staden, 11,12 and used for with sensors capable to perform in more than one mode, e.g., for DPV measurements and stochastic measurements, or potentiometric and stochastic measurements. The main benefit of these sensors is the possibility of quantifying twice the analyte in the same sample, with the same sensors, these type of measurements increasing the degree of confidence in the accuracy of determination.…”

“…Garanty-Bogakca and coworkers determined the effect of weight loss in response to a lifestyle modification on the serum levels of inflammatory markers in obese children and adolescents. 7 IL-6 levels in serum were measured to date using the classical method enzyme-linked immunosorbent assay (ELISA), [8][9][10] but this method encounters difficulties, such as time consuming analysis, expensive reagents and only monoclonal antibodies can be used as matched pairs.…”