scholarly journals Amplification by host cell factors of a sequence contained within the herpes simplex virus 1 genome.

1990 ◽  
Vol 87 (23) ◽  
pp. 9441-9444 ◽  
Author(s):  
A. E. Sears ◽  
B. Roizman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Cell ◽  
Herpes Simplex Virus 1 ◽  
Host Cell Factors ◽  
Simplex Virus

scholarly journals Mechanisms of Host IFI16, PML, and Daxx Protein Restriction of Herpes Simplex Virus 1 Replication

2018 ◽  
Vol 92 (10) ◽  
Author(s):  
Philipp E. Merkl ◽  
Megan H. Orzalli ◽  
David M. Knipe
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Cell ◽  
Virus Replication ◽  
Mechanisms Of Action ◽  
Viral Dna ◽  
Herpes Simplex Virus 1 ◽  
Host Cell Factors ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTThe initial events after DNA virus infection involve a race between epigenetic silencing of the incoming viral DNA by host cell factors and expression of viral genes. Several host gene products, including the nuclear domain 10 (ND10) components PML (promyelocytic leukemia) and Daxx (death domain-associated protein 6), as well as IFI16 (interferon-inducible protein 16), have been shown to restrict herpes simplex virus 1 (HSV-1) replication. Whether IFI16 and ND10 components work together or separately to restrict HSV-1 replication is not known. To determine the combinatorial effects of IFI16 and ND10 proteins on viral infection, we depleted Daxx or PML in primary human foreskin fibroblasts (HFFs) in the presence or absence of IFI16. Daxx or IFI16 depletion resulted in higherICP0mutant viral yields, and the effects were additive. Surprisingly, small interfering RNA (siRNA) depletion of PML in the HFF cells led to decreased ICP0-null virus replication, while short hairpin RNA (shRNA) depletion led to increased ICP0-null virus replication, arguing that different PML isoforms or PML-related proteins may have restrictive or proviral functions. In normal human cells, viral DNA replication increases expression of all classes of HSV-1 genes. We observed that IFI16 repressed transcription from both parental and progeny DNA genomes. Taken together, our results show that the mechanisms of action of IFI16 and ND10 proteins are independent, at least in part, and that IFI16 exerts restrictive effects on both input and replicated viral genomes. These results raise the potential for distinct mechanisms of action of IFI16 on parental and progeny viral DNA molecules.IMPORTANCEMany human DNA viruses transcribe their genomes and replicate in the nucleus of a host cell, where they exploit the host cell nuclear machinery for their own replication. Host factors attempt to restrict viral replication by blocking such events, and viruses have evolved mechanisms to neutralize the host restriction factors. In this study, we provide information about the mechanisms of action of three host cell factors that restrict replication of herpes simplex virus (HSV). We found that these factors function independently and that one acts to restrict viral transcription from parental and progeny viral DNA genomes. These results provide new information about how cells counter DNA virus replication in the nucleus and provide possible approaches to enhance the ability of human cells to resist HSV infection.

scholarly journals A Functional Interaction between Herpes Simplex Virus 1 Glycoprotein gH/gL Domains I and II and gD Is Defined by Using Alphaherpesvirus gH and gL Chimeras

2015 ◽  
Vol 89 (14) ◽  
pp. 7159-7169 ◽  
Author(s):  
Qing Fan ◽  
Richard Longnecker ◽  
Sarah A. Connolly
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Cell ◽  
Current Model ◽  
Viral Envelope ◽  
Functional Interaction ◽  
Herpes Simplex Virus 1 ◽  
Homotypic Interaction ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTWhereas most viruses require only a single protein to bind to and fuse with cells, herpesviruses use multiple glycoproteins to mediate virus entry, and thus communication among these proteins is required. For most alphaherpesviruses, the minimal set of viral proteins required for fusion with the host cell includes glycoproteins gD, gB, and a gH/gL heterodimer. In the current model of entry, gD binds to a cellular receptor and transmits a signal to gH/gL. This signal then triggers gB, the conserved fusion protein, to insert into the target membrane and refold to merge the viral and cellular membranes. We previously demonstrated that gB homologs from two alphaherpesviruses, herpes simplex virus 1 (HSV-1) and saimiriine herpesvirus 1 (SaHV-1), were interchangeable. In contrast, neither gD nor gH/gL functioned with heterotypic entry glycoproteins, indicating that gD and gH/gL exhibit an essential type-specific functional interaction. To map this homotypic interaction site on gH/gL, we generated HSV-1/SaHV-1 gH and gL chimeras. The functional interaction with HSV-1 gD mapped to the N-terminal domains I and II of the HSV-1 gH ectodomain. The core of HSV-1 gL that interacts with gH also was required for functional homotypic interaction. The N-terminal gH/gL domains I and II are the least conserved and may have evolved to support species-specific glycoprotein interactions.IMPORTANCEThe first step of the herpesvirus life cycle is entry into a host cell. A coordinated interaction among multiple viral glycoproteins is required to mediate fusion of the viral envelope with the cell membrane. The details of how these glycoproteins interact to trigger fusion are unclear. By swapping the entry glycoproteins of two alphaherpesviruses (HSV-1 and SaHV-1), we previously demonstrated a functional homotypic interaction between gD and gH/gL. To define the gH and gL requirements for homotypic interaction, we evaluated the function of a panel of HSV-1/SaHV-1 gH and gL chimeras. We demonstrate that domains I and II of HSV-1 gH are sufficient to promote a functional, albeit reduced, interaction with HSV-1 gD. These findings contribute to our model of how the entry glycoproteins cooperate to mediate herpesvirus entry into the cell.

scholarly journals Host-Cell Lysosomal Response to Two Strains of Herpes Simplex Virus 1

1970 ◽  
Vol 5 (2) ◽  
pp. 226-229 ◽  
Author(s):  
D. L. Fine ◽  
R. S. Lake ◽  
E. H. Ludwig
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Cell ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus

scholarly journals Correction for Abrisch et al., Infection by Herpes Simplex Virus 1 Causes Near-Complete Loss of RNA Polymerase II Occupancy on the Host Cell Genome

2016 ◽  
Vol 90 (24) ◽  
pp. 11279-11279 ◽  
Author(s):  
Robert G. Abrisch ◽  
Tess M. Eidem ◽  
Petro Yakovchuk ◽  
Jennifer F. Kugel ◽  
James A. Goodrich
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Rna Polymerase ◽  
Host Cell ◽  
Rna Polymerase Ii ◽  
Complete Loss ◽  
Herpes Simplex Virus 1 ◽  
Cell Genome ◽  
Simplex Virus

scholarly journals HCFC1R1 Deficiency Blocks Herpes Simplex Virus-1 Infection by Inhibiting Nuclear Translocation of HCFC1 and VP16

2020 ◽  
Author(s):  
Yangkun Shen ◽  
Zhoujie Ye ◽  
Xiangqian Zhao ◽  
Zhihua Feng ◽  
Jinfeng Chen ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Cell ◽  
Host Cells ◽  
The Novel ◽  
Wild Type ◽  
Herpes Simplex Virus 1 ◽  
Novel Target ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTUpon HSV-1 infection, viral protein 16 (VP16), supported by Host Cell Factor C1 (HCFC1), is rapidly transported into the nucleus, and help to express a series of HSV-1 immediate-early proteins to begin its lytic replication. However, no direct evidence has shown if the HCFC1 deficiency can affect the proliferation of HSV-1 so far. Here, we showed that the HCFC1 deficiency led to a strong resistance to HSV-1 infection. Moreover, we identified Host Cell Factor C1 Regulator 1 (HCFC1R1) as a new host factor acting early in HSV infection for the transport of the HSV-1 capsid to the nucleus. The HCFC1R1 deficiency also led to a strong resistance to HSV-1 infection. The HCFC1R1 deficiency did not affect the attachment of HSV-1 to host cells but act early in HSV-1 infection by perturbing the formation of HCFC1/VP16 complex. Remarkably, in addition to wild-type HSV-1 infection, the host cells in the absence of either HCFC1 or HCFC1R1 showed strong resistant to the infection of TK-deficient HSV-1, which strain can course severe symptoms and tolerate to the current anti-HSV drug Acyclovir. Our data suggest that HCFC1 or HCFC1R1 may be used as the novel target for developing anti-HSV-1 therapies.IMPORTANCEHerpes simplex virus-1 (HSV-1) is widely spread in the human population and can cause a variety of herpetic diseases. Acyclovir, a guanosine analogue that targets the TK protein of HSV-1, is the first specific and selective anti-HSV-1 drug. However, the rapid emergence of resistant HSV-1 strains is occurring worldwide, endangering the efficacy of Acyclovir. Alternatively, targeting host factors is another strategy to stop HSV-1 infection. Unfortunately, although the HSV-1’s receptor, Nectin-1, was discovered in 1998, no effective antiviral drug to date has been developed by targeting Nectin-1. Targeting multiple pathways is the ultimate choice to prevent HSV-1 infection. Here we demonstrated that the deletion of HCFC1 or HCFC1R1 exhibits a strong inhibitory effect on both wild-type and TK-deficient HSV-1. Overall, we present evidence that HCFC1 or HCFC1R1 may be used as the novel target for developing anti-HSV-1 therapies with a defined mechanism of action.

scholarly journals Herpes Simplex Virus 1 UL31 and UL34 Gene Products Promote the Late Maturation of Viral Replication Compartments to the Nuclear Periphery

2004 ◽  
Vol 78 (11) ◽  
pp. 5591-5600 ◽  
Author(s):  
Martha Simpson-Holley ◽  
Joel Baines ◽  
Richard Roller ◽  
David M. Knipe
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Cell ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Dense Layer ◽  
Gene Products ◽  
Herpes Simplex Virus 1 ◽  
Nuclear Egress ◽  
Simplex Virus

ABSTRACT Herpes simplex virus 1 (HSV-1) forms replication compartments (RCs), domains in which viral DNA replication, late-gene transcription, and encapsidation take place, in the host cell nucleus. The formation of these domains leads to compression and marginalization of host cell chromatin, which forms a dense layer surrounding the viral RCs and constitutes a potential barrier to viral nuclear egress or primary envelopment at the inner nuclear membrane. Surrounding the chromatin layer is the nuclear lamina, a further host cell barrier to egress. In this study, we describe an additional phase in RC maturation that involves disruption of the host chromatin and nuclear lamina so that the RC can approach the nuclear envelope. During this phase, the structure of the chromatin layer is altered so that it no longer forms a continuous layer around the RCs but instead is fragmented, forming islands between which RCs extend to reach the nuclear periphery. Coincident with these changes, the nuclear lamina components lamin A/C and lamin-associated protein 2 appear to be redistributed via a mechanism involving the UL 31 and UL 34 gene products. Viruses in which the UL 31 or UL 34 gene has been deleted are unable to undergo this phase of chromatin reorganization and lamina alterations and instead form RCs which are bounded by an intact host cell chromatin layer and nuclear lamina. We postulate that these defects in chromatin restructuring and lamina reorganization explain the previously documented growth defects of these mutant viruses.

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