Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus Restriction Factor

Giovannoni, Federico; Damonte, Elsa B.

doi:10.1371/journal.pone.0125690

Cited by 24 publications

(23 citation statements)

References 48 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Promyelocytic leukemia was reported to have antiviral activities against a number of RNA viruses, such as the LCMV, rabies virus, poliovirus, encephalomyocarditis virus (EMCV), VSV, and DENV ( 13 , 14 , 18 , 27 , 28 ). To investigate the roles of PML in the replication of EV71, we determined the effects of the down-modulation of endogenous PML on EV71 replication.…”

Section: Resultsmentioning

confidence: 99%

“…PML KO mice become sensitive to infection including vesicular stomatitis virus (VSV), rabies virus, and arenavirus lymphocytic choriomeningitis virus (LCMV) ( 15 – 17 ). In a recent report, the antiviral activity of PML was observed in dengue virus (DENV)-2 infected-A549 cells ( 18 ). However, PML activity in enterovirus 71 (EV71) infection has not been documented to date.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Promyelocytic Leukemia Restricts Enterovirus 71 Replication by Inhibiting Autophagy

et al. 2018

View full text Add to dashboard Cite

The promyelocytic leukemia (PML) protein, also known as TRIM19, functions as a major organizer of PML nuclear bodies (NBs) in most mammalian cells and plays important roles in antiviral activities against both DNA and RNA viruses. In this study, we found that the downregulation of PML rendered HeLa cells more susceptible to infection by enterovirus 71 (EV71), and the overexpression of the PMLIII or PMLIV isoforms inhibited viral protein expression and resulted in viral titers that were 2–3 log units lower than those in the control. Using short interfering RNAs, the downregulation of either the PMLIII or PMLIV isoform increased both viral protein VP1 expression and viral production. The PML repression of EV71 replication was partially mediated by the inhibition of autophagy, and PML deficiency triggered autophagy. Furthermore, the EV71 infection resulted in a reduction in PML independent of the proteasome pathway. Instead, PML degradation was mediated by virus protease 3Cpro. In conclusion, PML contributes to a cellular antiviral effect by inhibiting autophagy, which is countered by a disruption of promyelocytic leukemia protein-nuclear bodies mediated by viral protease 3Cpro.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Promyelocytic Leukemia Restricts Enterovirus 71 Replication by Inhibiting Autophagy

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Without PML-NBs, these processes would be less efficient or not possible at all in the cytoplasm. Importantly, PML-NBs have shown to limit viral replication in several viral models through multiple mechanisms, and in consequence, many viruses encode products that modify the localization or eliminate PML-NBs in cultured cells (Geoffroy and Chelbi-Alix, 2011;Giovannoni et al, 2015;Brown et al, 2016;Schilling et al, 2017). PML is the major structural component of PML-NBs, and their stability depends on PML presence.…”

Section: Zikv Infection Promotes Pml-nbs Disruptionmentioning

confidence: 99%

Cellular Organelles Reorganization During Zika Virus Infection of Human Cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

Zika virus (ZIKV) is an enveloped positive stranded RNA virus belonging to the genus Flavivirus in the family Flaviviridae that emerged in recent decades causing pandemic outbreaks of human infections occasionally associated with severe neurological disorders in adults and newborns. The intracellular steps of flavivirus multiplication are associated to cellular membranes and their bound organelles leading to an extensive host cell reorganization. Importantly, the association of organelle dysfunction with diseases caused by several human viruses has been widely reported in recent studies. With the aim to increase the knowledge about the impact of ZIKV infection on the host cell functions, the present study was focused on the evaluation of the reorganization of three cell components, promyelocytic leukemia nuclear bodies (PML-NBs), mitochondria, and lipid droplets (LDs). Relevant human cell lines including neural progenitor cells (NPCs), hepatic Huh-7, and retinal pigment epithelial (RPE) cells were infected with the Argentina INEVH116141 ZIKV strain and the organelle alterations were studied by using fluorescent cell imaging analysis. Our results have shown that these three organelles are targeted and structurally modified during ZIKV infection. Considering the nuclear reorganization, the analysis by confocal microscopy of infected cells showed a significantly reduced number of PML-NBs in comparison to uninfected cells. Moreover, a mitochondrial morphodynamic perturbation with an increased fragmentation and the loss of mitochondrial membrane potential was observed in ZIKV infected RPE cells. Regarding lipid structures, a decrease in the number and volume of LDs was observed in ZIKV infected cells. Given the involvement of these organelles in host defense processes, the reported perturbations may be related to enhanced virus replication through protection from innate immunity. The understanding of the cellular remodeling will enable the design of new host-targeted antiviral strategies.

show abstract

“…Upon viral infection, the molecular patterns of viruses are detected by various cellular sensors including Toll-like receptors (TLRs) and intracellular helicases such as RIG-I and MDA5, which activate IFN-regulatory factors (IRFs) such as IRF3 to induce the expression of a spectrum of IFN-responsive genes. Typical IFNresponsive gene products include, e.g., protein kinase R (PKR), endoribonuclease L (RNase L), promyelocytic leukemia (PML) nuclear bodies, and cellular restriction factors [71,72]. Viruses have evolved various mechanisms to subvert the host immune response including, e.g.…”

Section: Immune Responsementioning

confidence: 99%

Orchestrated efforts on host network hijacking: Processes governing virus replication

et al. 2020

View full text Add to dashboard Cite

With the high pervasiveness of viral diseases, the battle against viruses has never ceased. Here we discuss five cellular processes, namely "autophagy", "programmed cell death", "immune response", "cell cycle alteration", and "lipid metabolic reprogramming", that considerably guide viral replication after host infection in an orchestrated manner. On viral infection, "autophagy" and "programmed cell death" are two dynamically synchronized cell survival programs; "immune response" is a cell defense program typically suppressed by viruses; "cell cycle alteration" and "lipid metabolic reprogramming" are two altered cell housekeeping programs tunable in both directions. We emphasize on their functionalities in modulating viral replication, strategies viruses have evolved to tune these processes for their benefit, and how these processes orchestrate and govern cell fate upon viral infection. Understanding how viruses hijack host networks has both academic and industrial values in providing insights toward therapeutic strategy design for viral disease control, offering useful information in applications that aim to use viral vectors to improve human health such as gene therapy, and providing guidelines to maximize viral particle yield for improved vaccine production at a reduced cost. ARTICLE HISTORY

show abstract

Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus Restriction Factor

Cited by 24 publications

References 48 publications

Promyelocytic Leukemia Restricts Enterovirus 71 Replication by Inhibiting Autophagy

Promyelocytic Leukemia Restricts Enterovirus 71 Replication by Inhibiting Autophagy

Cellular Organelles Reorganization During Zika Virus Infection of Human Cells

Orchestrated efforts on host network hijacking: Processes governing virus replication

Contact Info

Product

Resources

About