scholarly journals Swine Promyelocytic Leukemia Isoform II Inhibits Pseudorabies Virus Infection by Suppressing Viral Gene Transcription in PML-NBs

2020 ◽  
Author(s):  
Cuilian Yu ◽  
Aotian Xu ◽  
Yue Lang ◽  
Chao Qin ◽  
Xiufang Yuan ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Transcriptional Repression ◽  
Pseudorabies Virus ◽  
Cysteine Residue ◽  
Natural Host ◽  
Nuclear Bodies ◽  
Viral Gene ◽  
Viral Gene Transcription ◽  
C Terminus

ABSTRACTPromyelocytic leukaemia nuclear bodies (PML-NBs) possess an important intrinsic antiviral activity against α-herpesvirus infection. PML is the structural backbone of NBs, comprising different isoforms. However, the contribution of each isoform to α-herpesvirus restriction is not well understood. Here, we report the role of PML-NBs and swine PML (sPML) isoforms in pseudorabies virus (PRV) infection in its natural host swine cells. We found that sPML-NBs exhibit an anti-PRV activity in the context of increasing the expression level of endogenous sPML. Of four sPML isoforms cloned and examined, only isoform sPML-II/IIa, not sPML-I and IVa, expressed in a sPML knockout cells inhibits PRV infection. Both the unique 7b region of sPML-II and sumoylation-dependent normal formation of PML-NBs are required. 7b possesses a transcriptional repression activity and suppresses viral gene transcription during PRV infection with the cysteine residue 589 and 599 being critically involved. We conclude that sPML-NBs inhibit PRV infection by repressing viral gene transcription through the 7b region of sPML-II.IMPORTANCEPML-NBs are nuclear sites that mediate the antiviral restriction of α-herpesvirus gene expression and replication. However, the contrition of each PML isoform to this activity of PML-NBs is not well characterized. Using PRV and its natural host swine cells as a system, we have discovered that the unique C-terminus of sPML isoform II is required for PML-NBs to inhibit PRV infection by directly engaging in repression of viral gene transcription. Our study not only confirms in swine cells that PML-NBs have an anti-viral function, but also presents a mechanism to suggest that PML-NBs inhibit viral infection in an isoform specific manner.

scholarly journals Swine Promyelocytic Leukemia Isoform II Inhibits Pseudorabies Virus Infection by Suppressing Viral Gene Transcription in Promyelocytic Leukemia Nuclear Bodies

2020 ◽  
Vol 94 (18) ◽  
Author(s):  
Cuilian Yu ◽  
Aotian Xu ◽  
Yue Lang ◽  
Chao Qin ◽  
Mengdong Wang ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Transcriptional Repression ◽  
Pseudorabies Virus ◽  
Promyelocytic Leukemia ◽  
Natural Host ◽  
Nuclear Bodies ◽  
Viral Gene ◽  
Viral Gene Transcription ◽  
C Terminus ◽  
Promyelocytic Leukemia Nuclear Bodies

ABSTRACT Promyelocytic leukemia nuclear bodies (PML-NBs) possess an important intrinsic antiviral activity against alphaherpesvirus infection. PML is the structural backbone of NBs, comprising different isoforms. However, the contribution of each isoform to alphaherpesvirus restriction is not well understood. Here, we report the role of PML-NBs and swine PML (sPML) isoforms in pseudorabies virus (PRV) infection in its natural host swine cells. We found that sPML-NBs exhibit an anti-PRV activity in the context of increasing the expression level of endogenous sPML. Of four sPML isoforms cloned and examined, only isoforms sPML-II and -IIa, not sPML-I and -IVa, expressed in a sPML knockout cells inhibit PRV infection. Both the unique 7b region of sPML-II and the sumoylation-dependent normal formation of PML-NBs are required. 7b possesses a transcriptional repression activity and suppresses viral gene transcription during PRV infection with the cysteine residues 589 and 599 being critically involved. We conclude that sPML-NBs inhibit PRV infection partly by repressing viral gene transcription through the 7b region of sPML-II. IMPORTANCE PML-NBs are nuclear sites that mediate the antiviral restriction of alphaherpesvirus gene expression and replication. However, the contribution of each PML isoform to this activity of PML-NBs is not well characterized. Using PRV and its natural host swine cells as a system, we have discovered that the unique C terminus of sPML isoform II is required for PML-NBs to inhibit PRV infection by directly engaging in repression of viral gene transcription. Our study not only confirms in swine cells that PML-NBs have an antiviral function but also presents a mechanism to suggest that PML-NBs inhibit viral infection in an isoform specific manner.

scholarly journals Strategies to Inhibit Hepatitis B Virus at the Transcript Level

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1327
Author(s):  
Bingqian Qu ◽  
Richard J. P. Brown
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Gene Transcription ◽  
Antigen Expression ◽  
Transcript Level ◽  
Viral Gene ◽  
Small Interfering Rnas ◽  
Viral Gene Transcription ◽  
Hbv Vaccination ◽  
B Virus

Approximately 240 million people are chronically infected with hepatitis B virus (HBV), despite four decades of effective HBV vaccination. During chronic infection, HBV forms two distinct templates responsible for viral transcription: (1) episomal covalently closed circular (ccc)DNA and (2) host genome-integrated viral templates. Multiple ubiquitous and liver-specific transcription factors are recruited onto these templates and modulate viral gene transcription. This review details the latest developments in antivirals that inhibit HBV gene transcription or destabilize viral transcripts. Notably, nuclear receptor agonists exhibit potent inhibition of viral gene transcription from cccDNA. Small molecule inhibitors repress HBV X protein-mediated transcription from cccDNA, while small interfering RNAs and single-stranded oligonucleotides result in transcript degradation from both cccDNA and integrated templates. These antivirals mediate their effects by reducing viral transcripts abundance, some leading to a loss of surface antigen expression, and they can potentially be added to the arsenal of drugs with demonstrable anti-HBV activity. Thus, these candidates deserve special attention for future repurposing or further development as anti-HBV therapeutics.

scholarly journals The C-terminus of CBFβ-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis

Blood ◽  
2013 ◽  
Vol 121 (4) ◽  
pp. 638-642 ◽  
Author(s):  
Yasuhiko Kamikubo ◽  
R. Katherine Hyde ◽  
Ling Zhao ◽  
Lemlem Alemu ◽  
Cecilia Rivas ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Myeloid Leukemia ◽  
Single Copy ◽  
Full Length ◽  
Myeloproliferative Disease ◽  
Chromosome 16 ◽  
C Terminus ◽  
Acute Myeloid

Abstract The C-terminus of CBFβ-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for self-multimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBFβ-SMMHC. To test the role of the fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBFβ-SMMHC (CBFβ-SMMHCΔC95). Embryos with a single copy of CBFβ-SMMHCΔC95 were viable and showed no defects in hematopoiesis, whereas embryos homozygous for the CBFβ-SMMHCΔC95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBFβ-SMMHC. Importantly, unlike mice expressing full-length CBFβ-SMMHC, none of the mice expressing CBFβ-SMMHCΔC95 developed leukemia, even after treatment with a mutagen, although some of the older mice developed a nontransplantable myeloproliferative disease. Our data indicate that the CBFβ-SMMHC's C-terminus is essential to induce embryonic hematopoietic defects and leukemogenesis.

scholarly journals Evaluation of Cyprinid Herpesvirus 2 Latency and Reactivation in Carassius gibel

2020 ◽  
Vol 8 (3) ◽  
pp. 445
Author(s):  
Wenjun Chai ◽  
Lin Qi ◽  
Yujun Zhang ◽  
Mingming Hong ◽  
Ling Jin ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Genomic Dna ◽  
Primary Infection ◽  
Trichostatin A ◽  
Acute Infection ◽  
Culture Conditions ◽  
Gibel Carp ◽  
Viral Gene ◽  
Viral Gene Transcription

Cyprinid herpesvirus 2 (CyHV-2, species Cyprinid herpesvirus 2) causes severe mortality in ornamental goldfish, crucian carp (Carassius auratus), and gibel carp (Carassius gibelio). It has been shown that the genomic DNA of CyHV-2 could be detected in subclinical fish, which implied that CyHV-2 could establish persistent infection. In this study, the latency of CyHV-2 was investigated in the survival fish after primary infection. CyHV-2 genomic DNA was detected in multiple tissues of acute infection samples; however, detection of CyHV-2 DNA was significantly reduced in fish recovered from the primary infection on day 300 postinfection. No active viral gene transcription, such as DNA polymerase and ORF99, was detected in recovered fish. Following temperature stress, an increase of CyHV-2 DNA copy numbers and gene transcription were observed in tissues examined, which suggests that CyHV-2 was reactivated under stress. In addition, a cell line (GCBLat1) derived from the brain tissue from CyHV-2-exposed fish harbored CyHV-2 genome but did not produce infectious virions under normal culture conditions. However, CyHV-2 replication and viral gene transcription occurred when GCBLat1 cells were treated with trichostatin A (TSA) or phorbol 12-myristate 13-acetate (TPA). It suggests CyHV-2 can remain latent in vitro and can reactivate under stress condition.

scholarly journals BRD4 is associated with raccoon polyomavirus genome and mediates viral gene transcription and maintenance of a stem cell state in neuroglial tumour cells

2016 ◽  
Vol 97 (11) ◽  
pp. 2939-2948 ◽  
Author(s):  
Molly E. Church ◽  
Marko Estrada ◽  
Christian M. Leutenegger ◽  
Florante N. Dela Cruz ◽  
Patricia A. Pesavento ◽  
...  
Keyword(s):  
Stem Cell ◽  
Gene Transcription ◽  
Tumour Cells ◽  
Viral Gene ◽  
Viral Gene Transcription ◽  
Cell State ◽  
Stem Cell State

scholarly journals Alpha interferon suppresses hepatitis B virus enhancer activity and reduces viral gene transcription.

1990 ◽  
Vol 64 (4) ◽  
pp. 1821-1824 ◽  
Author(s):  
R Tur-Kaspa ◽  
L Teicher ◽  
O Laub ◽  
A Itin ◽  
D Dagan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Gene Transcription ◽  
Alpha Interferon ◽  
Viral Gene ◽  
Enhancer Activity ◽  
Viral Gene Transcription ◽  
B Virus

scholarly journals Whitefly HES1 binds to the intergenic region of Tomato yellow leaf curl China virus and promotes viral gene transcription

Virology ◽  
2020 ◽  
Vol 542 ◽  
pp. 54-62 ◽  
Author(s):  
Yu-Meng Wang ◽  
Ya-Zhou He ◽  
Xin-Tong Ye ◽  
Wen-Ze He ◽  
Shu-Sheng Liu ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Intergenic Region ◽  
Tomato Yellow Leaf ◽  
Viral Gene ◽  
Yellow Leaf ◽  
Viral Gene Transcription ◽  
Leaf Curl

scholarly journals Regulation of Gene Transcription by the Histone H2A N-Terminal Domain

2007 ◽  
Vol 27 (21) ◽  
pp. 7641-7648 ◽  
Author(s):  
Michael A. Parra ◽  
John J. Wyrick
Keyword(s):  
Gene Transcription ◽  
Microarray Data ◽  
Transcriptional Repression ◽  
Dna Microarrays ◽  
Reporter Genes ◽  
Histone H2a ◽  
Terminal Domain ◽  
Genome Wide ◽  
Genome Wide Expression

ABSTRACT Histone N-terminal domains play critical roles in regulating chromatin structure and gene transcription. Relatively little is known, however, about the role of the histone H2A N-terminal domain in transcription regulation. We have used DNA microarrays to characterize the changes in genome-wide expression caused by mutations in the N-terminal domain of histone H2A. Our results indicate that the N-terminal domain of histone H2A functions primarily to repress the transcription of a large subset of the Saccharomyces cerevisiae genome and that most of the H2A-repressed genes are also repressed by the histone H2B N-terminal domain. Using the histone H2A microarray data, we selected three reporter genes (BNA1, BNA2, and GCY1), which we subsequently used to map regions in the H2A N-terminal domain responsible for this transcriptional repression. These studies revealed that a small subdomain in the H2A N-terminal tail, comprised of residues 16 to 20, is required for the transcriptional repression of these reporter genes. Deletion of either the entire histone H2A N-terminal domain or just this small subdomain imparts sensitivity to UV irradiation. Finally, we show that two residues in this H2A subdomain, serine-17 and arginine-18, are specifically required for the transcriptional repression of the BNA2 reporter gene.

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