Further Characterization of the Potent and Prolonged Inhibition of Herpes Simplex Virus Replication in Human Cell Lines by Penciclovir

1996 ◽  
Vol 7 (3) ◽  
pp. 128-137 ◽  
Author(s):  
T.H. Bacon ◽  
B.A. Howard
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Virus Replication ◽  
Human Cell ◽  
Human Cell Lines ◽  
Potent Inhibition ◽  
Multiple Cycles ◽  
Simplex Virus ◽  
Hsv 1

The replication of herpes simplex virus type 1 (HSV-1) or HSV-2 in MRC-5 cells infected at 0.01 pfu cell−1 treated continuously for 72 h, was inhibited more efficiently by penciclovir than aciclovir ( p = 0.0001). However, multiple cycles of replication were required in order to distinguish the compounds. Virus from cultures treated for 72 h with either compound, at 3 or 10 μg ml−1 was resistant to penciclovir and aciclovir (50% effective concentrations > 10 μg ml−1), but infectivity titres of supernatants from these aciclovirtreated cultures were higher than for penciclovir. Increased production of resistant virus in aciclovirtreated cultures may be the consequence of the less potent inhibition of virus replication by aciclovir. Penciclovir caused prolonged inhibition of HSV-1 and HSV-2 replication in three human cell lines infected at 1 pfu cell−1 following treatment for 18 h, whereas virus replication resumed rapidly after withdrawal of aciclovir. Neither compound showed prolonged activity after 18 h treatment, when the multiplicity of infection was reduced to 0.01 pfu cell−1. This surprising observation prompted experiments testing the effect of repeated pulse treatment in cultures infected at low multiplicity. Penciclovir inhibited HSV-1 replication significantly more effectively than aciclovir in MRC-5 cells infected at 10−4 pfu cell−1 treated daily for 6 h ( p < 0.001, n = 5) but only a trend was observed for HSV-2 ( p = 0.06, n = 6).

scholarly journals Novel, Soluble Isoform of the Herpes Simplex Virus (HSV) Receptor Nectin1 (or PRR1-HIgR-HveC) Modulates Positively and Negatively Susceptibility to HSV Infection

2001 ◽  
Vol 75 (12) ◽  
pp. 5684-5691 ◽  
Author(s):  
Marc Lopez ◽  
Francesca Cocchi ◽  
Elisa Avitabile ◽  
Annouck Leclerc ◽  
Jose Adelaide ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Alternative Splicing ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Human Cell ◽  
Culture Medium ◽  
Human Tissues ◽  
Human Cell Lines ◽  
Membrane Bound ◽  
Simplex Virus

ABSTRACT A novel member of the nectin family, nectin1γ, was molecularly cloned. The cDNA has the same ectodomain as nectin1α and nectin1β, the two known transmembrane isoforms that serve as receptors for herpes simplex virus (HSV) entry into human cell lines (nectin1α and nectin1β, also called PRR1-HveC and HIgR, respectively). The 1.4-kb transcript, which originated by alternative splicing, is expressed in human cell lines, and appears to have a narrow distribution in human tissues. The sequence does not have a hydrophobic anchoring region, and the protein is secreted in the culture medium of cells transfected with the cDNA. Nectin1γ, purified from culture medium, can compete with membrane-bound nectin1β and reduce HSV infectivity. The expression of nectin1γ cDNA in cells resistant to HSV infection and lacking HSV receptors enables HSV to enter the cell, which implies that it is present at the cell surface. Thus, nectin1γ has the potential both to mediate and to reduce HSV entry into cells.

scholarly journals BX795 demonstrates potent antiviral benefits against herpes simplex Virus-1 infection of human cell lines

2020 ◽  
Vol 180 ◽  
pp. 104814
Author(s):  
Aqsa Iqbal ◽  
Rahul Suryawanshi ◽  
Tejabhiram Yadavalli ◽  
Ipsita Volety ◽  
Deepak Shukla
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Human Cell ◽  
Human Cell Lines ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus

scholarly journals Relative Contributions of Herpes Simplex Virus 1 ICP0 and vhs to Loss of Cellular IFI16 Vary in Different Human Cell Types

2016 ◽  
Vol 90 (18) ◽  
pp. 8351-8359 ◽  
Author(s):  
Megan H. Orzalli ◽  
Nicole M. Broekema ◽  
David M. Knipe
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Human Cell ◽  
Hela Cells ◽  
Viral Gene ◽  
Herpes Simplex Virus 1 ◽  
Protein Levels ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTThe herpes simplex virus 1 (HSV-1) ICP0 protein is an E3 ubiquitin ligase that promotes the degradation of several host cell proteins. Most studies have found that ICP0 promotes the loss of IFI16 in infected cells, but one study reported that ICP0 was not necessary or sufficient for loss of IFI16 in a tumor-derived cell line. Therefore, in this study, we examined the requirement for ICP0 in promoting the loss of IFI16 in several normal and tumor-derived cell lines. HSV-1 infection resulted in an observable decrease of IFI16 protein levels in normal human foreskin fibroblasts (HFFs), normal oral keratinocytes (NOKs), and HeLa cells but not in U2OS cells. During infection with an ICP0-null virus, we observed a reduced loss of IFI16 in HFFs and NOKs but not in HeLa cells. Ectopic expression of ICP0 from a transfected plasmid was sufficient to promote the loss of IFI16 in HFFs and NOKs. In the absence of ICP0, we observed a delayed reduction of IFI16 protein that correlated with a reduction in the steady-state levels ofIFI16mRNA. In addition, we show that the ICP0-independent loss of IFI16 in HeLa cells is dependent in part on the activity of the viral virion host shutoff (vhs) tegument protein. Together, these results demonstrate that HSV-1 promotes the loss of IFI16 through at least two mechanisms: (i) by ICP0-dependent degradation of IFI16 and (ii) by vhs-dependent turnover ofIFI16mRNA. In addition, this study highlights a potential intrinsic difference between normal and tumor-derived cells for the activities of IFI16 and HSV-1 ICP0.IMPORTANCEHSV-1 is a ubiquitous virus that establishes a lifetime persistent infection in humans. The relative success of HSV-1 as a pathogen is, in part, dependent on the expression of viral proteins that counteract host intrinsic defense mechanisms and that modulate immune responses during viral infection. In this study, we examined the relative roles of two viral gene products for the ability to promote loss of the antiviral IFI16 DNA sensor. We demonstrate that the viral immediate early ICP0 protein plays a dominant role in the loss of IFI16 in normal, but not tumor-derived, human cell lines. In contrast, viral vhs-mediated loss of IFI16 by mRNA destabilization is revealed to be dominant in tumor-derived cells in which ICP0 is nonfunctional. Together, these results contribute to our understanding of how HSV-1 modulates IFI16 protein levels and highlight cell-type-dependent differences between normal and tumor-derived cells.

Interaction of Herpes Simplex Virus with Human Cell Lines at Various Stages of Lymphoid Differentiation

Intervirology ◽  
1981 ◽  
Vol 16 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Ehud Katz ◽  
Stella Mitrani-Rosenbaum ◽  
Eva Margalith ◽  
Hannah Ben-Bassaf
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Human Cell ◽  
Human Cell Lines ◽  
Simplex Virus

scholarly journals Control of Herpes Simplex Virus Replication Is Mediated through an Interferon Regulatory Factor 3-Dependent Pathway

2009 ◽  
Vol 83 (23) ◽  
pp. 12399-12406 ◽  
Author(s):  
Vineet D. Menachery ◽  
David A. Leib
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Replication ◽  
Early Recognition ◽  
Critical Role ◽  
Type I ◽  
Type I Ifn ◽  
Regulatory Factor ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The type I interferon (IFN) cascade is critical in controlling viral replication and pathogenesis. Recognition pathways triggered by viral infection rapidly induce the type I IFN cascade, often in an IFN regulatory factor 3 (IRF-3)-dependent fashion. This dependence predicts that loss of IRF-3 would render early recognition pathways inoperative and thereby impact virus replication, but this has not been observed previously with herpes simplex virus type 1 (HSV-1) in vitro. In this study, HSV-1-infected IRF-3−/− bone marrow-derived dendritic cells (BMDCs) and macrophages supported increased HSV replication compared to control cells. In addition, IRF-3-deficient BMDCs exhibited delayed type I IFN synthesis compared to control cells. However, while IFN pretreatment of IRF-3−/− BMDCs resulted in reduced virus titers, a far greater reduction was seen after IFN treatment of wild-type cells. This suggests that even in the presence of exogenously supplied IFN, IRF-3−/− BMDCs are inherently defective in the control of HSV-1 replication. Together, these results demonstrate a critical role for IRF-3-mediated pathways in controlling HSV-1 replication in cells of the murine immune system.

scholarly journals Combinations of Antiviral and Anti-Inflammatory Preparations for the Topical Treatment of Herpes Simplex Virus Assessed using a Murine Zosteriform Infection Model

1998 ◽  
Vol 9 (1) ◽  
pp. 19-24 ◽  
Author(s):  
AR Awan ◽  
J Harmenberg ◽  
O Flink ◽  
HJ Field
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Replication ◽  
Immune Cells ◽  
Clinical Signs ◽  
Infection Model ◽  
Virus Clearance ◽  
Anti Inflammatory ◽  
Simplex Virus ◽  
Hsv 1

Recently we have reported a zosteriform murine infection model which employs the adoptive transfer of immune cells (ATI) to recipient infected mice to produce a disease that mimics human recurrent herpes simplex virus (HSV) disease. Mice were infected with HSV-1 by scarification at the lateroventral line of the neck; 2 days later, the mice received immune cells from HSV-1-infected syngeneic mice. Although virus was cleared more quickly from the target tissues of virus replication in recipient mice, ATI resulted in a heightened inflammatory response and delayed healing. This model was used to test the effects of topical formulations containing foscarnet and/or the anti-inflammatory agent, hydrocortisone. Virus clearance and clinical signs, including ear thickness and zosteriform spread of lesions, were studied. Treatment with 3% foscarnet accelerated virus clearance but had little effect on clinical parameters. By contrast, 0.5% hydrocortisone increased the titre and extended the presence of infectious virus for at least 6 days, although the reduction in clinical signs was greater than that obtained with topical foscarnet. Foscarnet in combination with hydrocortisone produced a marked reduction in clinical signs while virus replication was reduced. These results are discussed in relation to the inflammation and discomfort experienced by patients and a possible role for anti-inflammatory formulations in the treatment of HSV reactivation episodes in man.

scholarly journals Reactivation of Expression from Quiescent Herpes Simplex Virus Type 1 Genomes in the Absence of Immediate-Early Protein ICP0

2007 ◽  
Vol 81 (21) ◽  
pp. 11781-11789 ◽  
Author(s):  
Chris M. Preston
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Replication ◽  
Human Fibroblasts ◽  
Protein Icp0 ◽  
Simplex Virus ◽  
Null Mutants ◽  
Hsv 1

ABSTRACT Model systems have previously been developed in which herpes simplex virus (HSV) is retained in human fibroblasts in a nonreplicating state known as quiescence. The HSV type 1 (HSV-1) immediate-early (IE) protein ICP0, an important activator of gene expression, reactivates the quiescent genome and promotes the resumption of virus replication. Previous studies reported that infection with ICP0-null HSV-1 mutants fails to reactivate quiescent HSV, even when the mutant itself undergoes productive replication, leading to the hypothesis that quiescent genomes exist in a silent configuration in which they are shielded from trans-acting factors. I reinvestigated these findings, using HSV-1 mutants with lesions in the transcription activators VP16, ICP0, and ICP4 to establish quiescent infection at high efficiency. Superinfection with ICP0-null HSV-1 mutants at a low multiplicity of infection (MOI), so that individual plaques were formed, reactivated expression from the quiescent genome, demonstrating that the requirement for ICP0 is not absolute. The previously reported failure to observe reactivation by ICP0-null mutants was shown to be a consequence of either a low initial MOI or a high superinfecting MOI. Competition between viral genomes at the level of gene expression and virus replication, especially when ICP0 was absent, was demonstrated during reactivation and also during normal infection of human fibroblasts. The results show that the multiplicity-dependent phenotype of ICP0-null mutants limits the efficiency of reactivation at low MOIs and that competition between genomes occurs at high MOIs. The conclusion that quiescent HSV genomes are extensively silenced and intrinsically insensitive to trans-acting factors must be reevaluated.

scholarly journals The Murine Homolog (Mph) of Human Herpesvirus Entry Protein B (HveB) Mediates Entry of Pseudorabies Virus but Not Herpes Simplex Virus Types 1 and 2

1999 ◽  
Vol 73 (5) ◽  
pp. 4493-4497 ◽  
Author(s):  
Deepak Shukla ◽  
Cynthia L. Rowe ◽  
Yanzhang Dong ◽  
Vincent R. Racaniello ◽  
Patricia G. Spear
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Lines ◽  
Pseudorabies Virus ◽  
Human Herpesvirus ◽  
Mouse Cell ◽  
Poliovirus Receptor ◽  
Simplex Virus ◽  
Protein B ◽  
Hsv 1

ABSTRACT A mouse member of the immunoglobulin superfamily, originally designated the murine poliovirus receptor homolog (Mph), was found to be a receptor for the porcine alphaherpesvirus pseudorabies virus (PRV). This mouse protein, designated here murine herpesvirus entry protein B (mHveB), is most similar to one of three related human alphaherpesvirus receptors, the one designated HveB and also known as poliovirus receptor-related protein 2. Hamster cells resistant to PRV entry became susceptible upon expression of a cDNA encoding mHveB. Anti-mHveB antibody and a soluble protein composed of the mHveB ectodomain inhibited mHveB-dependent PRV entry. Expression of mHveB mRNA was detected in a variety of mouse cell lines, but anti-mHveB antibody inhibited PRV infection in only a subset of these cell lines, indicating that mHveB is the principal mediator of PRV entry into some mouse cell types but not others. Coexpression of mHveB with PRV gD, but not herpes simplex virus type 1 (HSV-1) gD, inhibited entry activity, suggesting that PRV gD may interact directly with mHveB as a ligand that can cause interference. By analogy with HSV-1, envelope-associated PRV gD probably also interacts directly with mHveB during viral entry.

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