scholarly journals Nuclear Translocation and Activation of the Transcription Factor NFAT Is Blocked by Herpes Simplex Virus Infection

2001 ◽  
Vol 75 (20) ◽  
pp. 9955-9965 ◽  
Author(s):  
Emily S. Scott ◽  
Sophie Malcomber ◽  
Peter O'Hare
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nuclear Import ◽  
Nuclear Translocation ◽  
Interleukin 2 ◽  
Early Gene ◽  
Nuclear Accumulation ◽  
Regulation Of Transcription ◽  
Infected Cells ◽  
Simplex Virus

ABSTRACT Transcription factors of the NFAT (nuclear factor of activated T cells) family are expressed in most immune system cells and in a range of other cell types. Signaling through NFAT is implicated in the regulation of transcription for the immune response and other processes, including differentiation and apoptosis. NFAT normally resides in the cytoplasm, and a key aspect of the NFAT activation pathway is the regulation of its nuclear import by the Ca2+/calmodulin-dependent phosphatase calcineurin. In a cell line stably expressing green fluorescent protein (GFP)-NFAT, this import can be triggered by elevation of intracellular calcium and visualized in live cells. Here we show that the inducible nuclear import of GFP-NFAT is efficiently blocked at early stages of herpes simplex virus (HSV) infection. This is a specific effect, since we observed abundant nuclear accumulation of a test viral protein and no impediment to general nuclear localization signal-dependent nuclear import and retention in infected cells. We show that virus binding at the cell surface is not itself sufficient to inhibit the signaling that induces NFAT nuclear translocation. Since the block occurs following infection in the presence of phosphonoacetic acid but not cycloheximide, we infer that the entry of the virion and early gene transcription are required but the effect is independent of DNA replication or late virus gene expression. A consequence of the block to GFP-NFAT import is a reduction in NFAT-dependent transcriptional activation from the interleukin-2 promoter in infected cells. This HSV-mediated repression of the NFAT pathway may constitute an immune evasion strategy or subversion of other NFAT-dependent cellular processes to promote viral replication.

Nuclear accumulation of a heat-shock 70-like protein during herpes simplex virus replication

1987 ◽  
Vol 7 (6) ◽  
pp. 475-483 ◽  
Author(s):  
Nicholas B. LaThangue ◽  
David S. Latchman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Lytic Infection ◽  
Cellular Stress Response ◽  
Productive Infection ◽  
Nuclear Accumulation ◽  
Infected Cells ◽  
Rnase Treatment ◽  
Simplex Virus

A monoclonal antibody defines an antigen, p68, related to hsp70, which is located in nuclei of uninfected exponential cells. Nuclear p68 is released by DNase but not RNase treatment suggesting an association with DNA. Lytic productive infection of confluent quiescent BHK 21 cells with herpes simplex virus type-2 causes p68 to accumulate in nuclei. The effect is specific for HSV-2, and does not occur in HSV-1 infected cells. Maximum nuclear accumulation of p68 requires virus DNA synthesis although a significant accumulation occurs in the absence of such synthesis. It is suggested that the nuclear accumulation of p68 is an aspect of a cellular stress response to lytic infection with HSV-2.

scholarly journals Downregulation of Cellular c-Jun N-Terminal Protein Kinase and NF-κB Activation by Berberine May Result in Inhibition of Herpes Simplex Virus Replication

2014 ◽  
Vol 58 (9) ◽  
pp. 5068-5078 ◽  
Author(s):  
Siwei Song ◽  
Min Qiu ◽  
Ying Chu ◽  
Deyan Chen ◽  
Xiaohui Wang ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Protein Kinase ◽  
Nuclear Translocation ◽  
Replication Cycle ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Dependent Manner ◽  
Viral Attachment ◽  
Simplex Virus

ABSTRACTBerberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. Some reports show that berberine exhibits anti-inflammatory, antitumor, and antiviral properties by modulating multiple cellular signaling pathways, including p53, nuclear factor κB (NF-κB), and mitogen-activated protein kinase. In the present study, we investigated the antiviral effect of berberine against herpes simplex virus (HSV) infection. Current antiherpes medicines such as acyclovir can lessen the recurring activation when used early at infection but are unable to prevent or cure infections where treatment has selected for resistant mutants. In searching for new antiviral agents against herpesvirus infection, we found that berberine reduced viral RNA transcription, protein synthesis, and virus titers in a dose-dependent manner. To elucidate the mechanism of its antiviral activity, the effect of berberine on the individual steps of viral replication cycle of HSV was investigated via time-of-drug addition assay. We found that berberine acted at the early stage of HSV replication cycle, between viral attachment/entry and genomic DNA replication, probably at the immediate-early gene expression stage. We further demonstrated that berberine significantly reduced HSV-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. Moreover, we found that berberine also depressed HSV-induced c-Jun N-terminal kinase (JNK) phosphorylation but had little effect on p38 phosphorylation. Our results suggest that the berberine inhibition of HSV infection may be mediated through modulating cellular JNK and NF-κB pathways.

Assembly of VP26 in herpes simplex virus-1 capsid implicated by 3-D structure of recombinant capsid

1995 ◽  
Vol 53 ◽  
pp. 840-841
Author(s):  
Z. Hong Zhou ◽  
Jing He ◽  
Joanita Jakana ◽  
J. D. Tatman ◽  
Frazer J. Rixon ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
3D Structure ◽  
Structure Study ◽  
Herpes Simplex Virus 1 ◽  
Shell Proteins ◽  
Life Threatening ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus-1 (HSV-1) is a ubiquitous virus which is implicated in diseases ranging from self-curing cold sores to life-threatening infections. The 2500 Å diameter herpes virion is composed of a glycoprotein spike containing, lipid envelope, enclosing a protein layer (the tegument) in which is embedded the capsid (which contains the dsDNA genome). The B-, and A- and C-capsids, representing different morphogenetic stages in HSV-1 infected cells, are composed of 7, and 5 structural proteins respectively. The three capsid types are organized in similar T=16 icosahedral shells with 12 pentons, 150 hexons, and 320 connecting triplexes. Our previous 3D structure study at 26 Å revealed domain features of all these structural components and suggested probable locations for the outer shell proteins, VP5, VP26, VP19c and VP23. VP5 makes up most of both pentons and hexons. VP26 appeared to bind to the VP5 subunit in hexon but not to that in penton.

scholarly journals Engagement of the Lysine-Specific Demethylase/HDAC1/CoREST/REST Complex by Herpes Simplex Virus 1

2009 ◽  
Vol 83 (9) ◽  
pp. 4376-4385 ◽  
Author(s):  
Haidong Gu ◽  
Bernard Roizman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nuclear Bodies ◽  
Wild Type Virus ◽  
Viral Dna ◽  
Herpes Simplex Virus 1 ◽  
Lysine Specific Demethylase ◽  
Repressor Complex ◽  
Infected Cells ◽  
Simplex Virus

ABSTRACT Among the early events in herpes simplex virus 1 replication are localization of ICP0 in ND10 bodies and accumulation of viral DNA-protein complexes in structures abutting ND10. ICP0 degrades components of ND10 and blocks silencing of viral DNA, achieving the latter by dislodging HDAC1 or -2 from the lysine-specific demethylase 1 (LSD1)/CoREST/REST repressor complex. The role of this process is apparent from the observation that a dominant-negative CoREST protein compensates for the absence of ICP0 in a cell-dependent fashion. HDAC1 or -2 and the CoREST/REST complex are independently translocated to the nucleus once viral DNA synthesis begins. The focus of this report is twofold. First, we report that in infected cells, LSD1, a key component of the repressor complex, is partially degraded or remains stably associated with CoREST and is ultimately also translocated, in part, to the cytoplasm. Second, we examined the distribution of the components of the repressor complex and ICP8 early in infection in wild-type-virus- and ICP0 mutant virus-infected cells. The repressor component and ultimately ICP8 localize in structures that abut the ND10 nuclear bodies. There is no evidence that the two compartments fuse. We propose that ICP0 must dynamically interact with both compartments in order to accomplish its functions of degrading PML and SP100 and suppressing silencing of viral DNA through its interactions with CoREST. In turn, the remodeling of the viral DNA-protein complex enables recruitment of ICP8 and initiation of formation of replication compartments.

Adjuvant-independent enhanced immune responses to recombinant herpes simplex virus type 1 glycoprotein D by fusion with biologically active interleukin-2

Vaccine ◽  
1993 ◽  
Vol 11 (6) ◽  
pp. 629-636 ◽  
Author(s):  
Masatoshi Hazama ◽  
Aki Mayumi-Aono ◽  
Naoki Asakawa ◽  
Shun'ichi Kuroda ◽  
Shuji Hinuma ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Interleukin 2 ◽  
Biologically Active ◽  
Glycoprotein D ◽  
Simplex Virus

scholarly journals Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 196
Author(s):  
Sara Artusi ◽  
Emanuela Ruggiero ◽  
Matteo Nadai ◽  
Beatrice Tosoni ◽  
Rosalba Perrone ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Dna Replication ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Herpes Simplex Virus 1 ◽  
Tem Analysis ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed by biophysical analysis that TMPyP4 interacts with HSV-1 G4s, and inhibits polymerase progression in vitro; in infected cells, it displayed good antiviral activity which, however, was independent of inhibition of virus DNA replication or entry. At low TMPyP4 concentration, the virus released by the cells was almost null, while inside the cell virus amounts were at control levels. TEM analysis showed that virus particles were trapped inside cytoplasmatic vesicles, which could not be ascribed to autophagy, as proven by RT-qPCR, western blot, and immunofluorescence analysis. Our data indicate a unique mechanism of action of TMPyP4 against HSV-1, and suggest the unprecedented involvement of currently unknown G4s in viral or antiviral cellular defense pathways.

scholarly journals ICP0 Dismantles Microtubule Networks in Herpes Simplex Virus-Infected Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e10975 ◽  
Author(s):  
Mingyu Liu ◽  
Edward E. Schmidt ◽  
William P. Halford
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Infected Cells ◽  
Microtubule Networks ◽  
Simplex Virus
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