Abstract
Promyelocytic leukemia protein nuclear bodies (PML-NBs) are dynamic nuclear structures, shown to be important for herpesvirus replication; however, their role in regulating Marek’s disease virus (MDV) infection has not been studied. MDV is an oncogenic alphaherpesvirus that causes lymphoproliferative disease in chickens. MDV encodes a US3 serine/threonine protein kinase that is important for MDV replication and gene expression. In this study, we studied the role of MDV US3 in regulating PML-NBs. Using an immunofluorescence assay, we found that MDV US3 disrupts PML and SP100 in a kinase dependent manner. In addition, treatment with MG-132 (a proteasome inhibitor) could partially restore the levels of PML and SP100, suggesting that a cellular proteasome dependent degradation pathway is involved in MDV US3 induced disruption of PML and SP100. These findings provide the first evidence for the interplay between MDV proteins and PML-NBs.
Highlights
It has been reported that herpes simplex virus type 1 (HSV-1) encoded ICP0 protein contains an E3 ubiquitin ligase activity domain that could mediate the degradation of PML and SP100, and that this process is important for HSV-1 lytic replication and reactivation [7,8]; human cytomegalovirus (HCMV) encoded immediate early protein 1 (IE1) and IE2 have been shown to colocalize with and disrupt the PML-NBs, allowing for the efficient lytic replication of HCMV [9]; Epstein–Barr virus (EBV) encoded BZLF-1, a viral bZIP protein, has been reported to regulate virus replication by disrupting PML-NBs [10]; K-bZIP, encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV), localizes to PML-NBs to establish virus replication compartments [11,12], and PML has been identified as a positive factor for KSHV lytic replication [13]
To better understand the interplay between Marek’s disease virus (MDV) proteins and PML-NBs, we examined the role of US3 from a very virulent plus MDV strain (686) in regulating the distribution and levels of PML-NBs components, PML and SP100
Our results show that the transfection of wild type US3 or kinase dead US3 (US3-K220A) did not affect the subcellular distribution of PML (Figure 1A) and SP100 (Figure 2A)
Summary
The host utilizes various anti-viral mechanisms to limit virus replication and spread. Nuclear domain 10, known as promyelocytic leukemia protein nuclear bodies (PML-NBs), has been characterized as a host factor that restricts virus infection [1]. It has been reported that herpes simplex virus type 1 (HSV-1) encoded ICP0 protein contains an E3 ubiquitin ligase activity domain that could mediate the degradation of PML and SP100, and that this process is important for HSV-1 lytic replication and reactivation [7,8]; human cytomegalovirus (HCMV) encoded immediate early protein 1 (IE1) and IE2 have been shown to colocalize with and disrupt the PML-NBs, allowing for the efficient lytic replication of HCMV [9]; Epstein–Barr virus (EBV) encoded BZLF-1, a viral bZIP protein, has been reported to regulate virus replication by disrupting PML-NBs [10]; K-bZIP ( known as K8), encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV), localizes to PML-NBs to establish virus replication compartments [11,12], and PML has been identified as a positive factor for KSHV lytic replication [13]. (GaHV-2), is an oncogenic and highly contagious avian alphaherpesvirus that causes T
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