Limits...
A role for cytoplasmic PML in cellular resistance to viral infection.

McNally BA, Trgovcich J, Maul GG, Liu Y, Zheng P - PLoS ONE (2008)

Bottom Line: Although multiple PML splice variants exist, we demonstrate that the ratio of a subset of cytoplasmic PML isoforms lacking exons 5 & 6 is enriched in cells exposed to herpes simplex virus-1 (HSV-1).In particular, we demonstrate that a PML isoform lacking exons 5 & 6, called PML Ib, mediates the intrinsic cellular defense against HSV-1 via the cytoplasmic sequestration of the infected cell protein (ICP) 0 of HSV-1.The results herein highlight the importance of cytoplasmic PML and call for an alternative, although not necessarily exclusive, interpretation regarding the redistribution of PML that is seen in virally infected cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center, Columbus, Ohio, United States of America.

ABSTRACT
PML gene was discovered as a fusion partner with retinoic acid receptor (RAR) alpha in the t(15:17) chromosomal translocation associated with acute promyelocytic leukemia (APL). Nuclear PML protein has been implicated in cell growth, tumor suppression, apoptosis, transcriptional regulation, chromatin remodeling, DNA repair, and anti-viral defense. The localization pattern of promyelocytic leukemia (PML) protein is drastically altered during viral infection. This alteration is traditionally viewed as a viral strategy to promote viral replication. Although multiple PML splice variants exist, we demonstrate that the ratio of a subset of cytoplasmic PML isoforms lacking exons 5 & 6 is enriched in cells exposed to herpes simplex virus-1 (HSV-1). In particular, we demonstrate that a PML isoform lacking exons 5 & 6, called PML Ib, mediates the intrinsic cellular defense against HSV-1 via the cytoplasmic sequestration of the infected cell protein (ICP) 0 of HSV-1. The results herein highlight the importance of cytoplasmic PML and call for an alternative, although not necessarily exclusive, interpretation regarding the redistribution of PML that is seen in virally infected cells.

Show MeSH

Related in: MedlinePlus

cPML exerts an antiviral effect against HSV-1.(A). PML −/−, PML +/+, and PML−/− cells stably over-expressing PML Ib were exposed to 0.1 PFU/mL HSV-1 (F) and harvested 2, 12, and 24 h post infection. Viral titers were determined in Vero cells. (B). PML (−/−) cells were transfected with vector, PML I, PML Ib or co-transfected with PML I and PML Ib. Polyclonal cells were drug selected and exposed to 1.0 PFU/cell HSV-1 (F) infection. 24 h post infection, cells were harvested and Western blot analysis was performed using antibodies to ICP0, Us11, and β-Actin.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2386554&req=5

pone-0002277-g005: cPML exerts an antiviral effect against HSV-1.(A). PML −/−, PML +/+, and PML−/− cells stably over-expressing PML Ib were exposed to 0.1 PFU/mL HSV-1 (F) and harvested 2, 12, and 24 h post infection. Viral titers were determined in Vero cells. (B). PML (−/−) cells were transfected with vector, PML I, PML Ib or co-transfected with PML I and PML Ib. Polyclonal cells were drug selected and exposed to 1.0 PFU/cell HSV-1 (F) infection. 24 h post infection, cells were harvested and Western blot analysis was performed using antibodies to ICP0, Us11, and β-Actin.

Mentions: To determine whether the function of PMLIb depends on endogenous PML, PML Ib was transfected into PML−/− fibroblasts and compared with PML+/+ and PML−/− cells for their susceptibility to HSV. As shown in Fig. 5A, targeted mutation of PML caused an approximate 100-fold increase in HSV yield over a 24-hour period. Transfection of PMLIb, however, completely abrogated the increase. Thus, in this model, PMLIb is largely responsible for the anti-viral effect of the Pml locus.


A role for cytoplasmic PML in cellular resistance to viral infection.

McNally BA, Trgovcich J, Maul GG, Liu Y, Zheng P - PLoS ONE (2008)

cPML exerts an antiviral effect against HSV-1.(A). PML −/−, PML +/+, and PML−/− cells stably over-expressing PML Ib were exposed to 0.1 PFU/mL HSV-1 (F) and harvested 2, 12, and 24 h post infection. Viral titers were determined in Vero cells. (B). PML (−/−) cells were transfected with vector, PML I, PML Ib or co-transfected with PML I and PML Ib. Polyclonal cells were drug selected and exposed to 1.0 PFU/cell HSV-1 (F) infection. 24 h post infection, cells were harvested and Western blot analysis was performed using antibodies to ICP0, Us11, and β-Actin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2386554&req=5

pone-0002277-g005: cPML exerts an antiviral effect against HSV-1.(A). PML −/−, PML +/+, and PML−/− cells stably over-expressing PML Ib were exposed to 0.1 PFU/mL HSV-1 (F) and harvested 2, 12, and 24 h post infection. Viral titers were determined in Vero cells. (B). PML (−/−) cells were transfected with vector, PML I, PML Ib or co-transfected with PML I and PML Ib. Polyclonal cells were drug selected and exposed to 1.0 PFU/cell HSV-1 (F) infection. 24 h post infection, cells were harvested and Western blot analysis was performed using antibodies to ICP0, Us11, and β-Actin.
Mentions: To determine whether the function of PMLIb depends on endogenous PML, PML Ib was transfected into PML−/− fibroblasts and compared with PML+/+ and PML−/− cells for their susceptibility to HSV. As shown in Fig. 5A, targeted mutation of PML caused an approximate 100-fold increase in HSV yield over a 24-hour period. Transfection of PMLIb, however, completely abrogated the increase. Thus, in this model, PMLIb is largely responsible for the anti-viral effect of the Pml locus.

Bottom Line: Although multiple PML splice variants exist, we demonstrate that the ratio of a subset of cytoplasmic PML isoforms lacking exons 5 & 6 is enriched in cells exposed to herpes simplex virus-1 (HSV-1).In particular, we demonstrate that a PML isoform lacking exons 5 & 6, called PML Ib, mediates the intrinsic cellular defense against HSV-1 via the cytoplasmic sequestration of the infected cell protein (ICP) 0 of HSV-1.The results herein highlight the importance of cytoplasmic PML and call for an alternative, although not necessarily exclusive, interpretation regarding the redistribution of PML that is seen in virally infected cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center, Columbus, Ohio, United States of America.

ABSTRACT
PML gene was discovered as a fusion partner with retinoic acid receptor (RAR) alpha in the t(15:17) chromosomal translocation associated with acute promyelocytic leukemia (APL). Nuclear PML protein has been implicated in cell growth, tumor suppression, apoptosis, transcriptional regulation, chromatin remodeling, DNA repair, and anti-viral defense. The localization pattern of promyelocytic leukemia (PML) protein is drastically altered during viral infection. This alteration is traditionally viewed as a viral strategy to promote viral replication. Although multiple PML splice variants exist, we demonstrate that the ratio of a subset of cytoplasmic PML isoforms lacking exons 5 & 6 is enriched in cells exposed to herpes simplex virus-1 (HSV-1). In particular, we demonstrate that a PML isoform lacking exons 5 & 6, called PML Ib, mediates the intrinsic cellular defense against HSV-1 via the cytoplasmic sequestration of the infected cell protein (ICP) 0 of HSV-1. The results herein highlight the importance of cytoplasmic PML and call for an alternative, although not necessarily exclusive, interpretation regarding the redistribution of PML that is seen in virally infected cells.

Show MeSH
Related in: MedlinePlus