Strain-dependent structural variants of herpes simplex virus type 1 ICP34.5 determine viral plaque size, efficiency of glycoprotein processing, and viral release and neuroinvasive disease potential.
*Genetic Variation; Animals; Cercopithecus aethiops; Cultured; Encephalitis; Genetic; Herpes Simplex/*physiopathology/virology; Herpesvirus 1; Human/*classification/genetics/*pathogenicity; Inbred BALB C; Male; Mice; Recombination; Transfection; Tumor Cells; Vero Cells; Viral Envelope Proteins/metabolism; Viral Plaque Assay; Viral Proteins/*chemistry/*genetics/metabolism
The ability of certain strains of herpes simplex virus type 1 (HSV-1) to cause encephalitis or neuroinvasive disease in the mouse upon peripheral infection is dependent on a combination of activities of specific forms of viral proteins. The importance of specific variants of ICP34.5 to neuroinvasive disease potential and its correlation with small-plaque production, inefficient glycoprotein processing, and virus release were suggested by comparison of ICP34.5 from the SP7 virus, originally obtained from the brain of a neonate with disseminated disease, and the tissue culture-passaged progeny of SP7 (SLP5 and SLP10) and the KOS321 virus. SLP5, SLP10, and KOS321 are attenuated and exhibit a large-plaque phenotype, including efficient glycoprotein processing and viral release. We show that expression of the KOS321 ICP34.5 protein in cells infected with SP7 or ICP34.5 deletion mutants promotes large plaque formation and efficient viral glycoprotein processing, while expression of the SP7 ICP34.5 protein decreases efficiency of viral glycoprotein processing. In addition, a recombinant virus, 4hS1, with the SP7 ICP34.5 gene replacing the KOS321-like ICP34.5 gene in the SLP10a background, rescues the small-plaque phenotype and neuroinvasive disease. The major difference in the ICP34.5 gene product is the number of Pro-Ala-Thr repeats in the middle region of the protein, with 18 for SP7 and 3 for KOS321. Strain-dependent differences in the ICP34.5 protein can therefore alter the tissue culture behavior and the virulence of HSV-1.
Mao Hanwen; Rosenthal Ken S
Journal of virology
2003
2003-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1128/jvi.77.6.3409-3417.2003" target="_blank" rel="noreferrer noopener">10.1128/jvi.77.6.3409-3417.2003</a>
Resveratrol inhibition of varicella-zoster virus replication in vitro.
Antiviral Agents/*pharmacology; Blotting; Cell Line; Dose-Response Relationship; Drug; Fibroblasts/virology; Herpesvirus 3; Human/*drug effects/physiology; Humans; Immediate-Early Proteins/biosynthesis; Messenger/biosynthesis; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; RNA; Stilbenes/*pharmacology; Trans-Activators/biosynthesis; Viral Envelope Proteins/biosynthesis; Viral Plaque Assay; Viral/biosynthesis; Virus Attachment/drug effects; Virus Inactivation/drug effects; Virus Replication/*drug effects; Western
Resveratrol was found to inhibit varicella-zoster virus (VZV) replication in a dose-dependent and reversible manner. This decrease in virus production in the presence of resveratrol was not caused by direct inactivation of VZV or inhibition of virus attachment to MRC-5 cells. The drug effectively limited VZV replication if added during the first 30 h of infection. Western blot analysis and real-time RT-PCR studies demonstrated that protein and mRNA levels of IE62, an essential immediate early viral protein, were reduced when compared to controls. These results demonstrate that VZV replication is adversely affected by resveratrol which is negatively impacting IE62 synthesis.
Docherty John J; Sweet Thomas J; Bailey Erin; Faith Seth A; Booth Tristan
Antiviral research
2006
2006-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.antiviral.2006.07.004" target="_blank" rel="noreferrer noopener">10.1016/j.antiviral.2006.07.004</a>
Effect of resveratrol on herpes simplex virus vaginal infection in the mouse.
Animals; Antiviral Agents/administration & dosage/pharmacology/*therapeutic use; Drug Evaluation; Female; Herpes Genitalis/*drug therapy/pathology/virology; Herpesvirus 1; Herpesvirus 2; Human/*drug effects/physiology; Human/drug effects/isolation & purification/physiology; Mice; Placebos; Preclinical; Resveratrol; Stilbenes/administration & dosage/pharmacology/*therapeutic use; Survival Analysis; Vaginal Diseases/*drug therapy/virology; Viral Plaque Assay; Virus Replication/drug effects
Resveratrol (3,5,4'-trihydroxystilbene) is a natural component of certain foods, such as grapes, that, when topically applied, has been shown to limit HSV-1 lesion formation in the skin of mice [Antiviral Res. 61:19-26, 2004]. To determine if it is active on genital HSV infection, the vagina of mice were infected with HSV-2 or HSV-1 and treated with a cream formulation of resveratrol. Mice were evaluated daily for extravaginal disease and vaginal swabs were taken regularly and assayed for infectious virus. Initial studies demonstrated that 19% resveratrol cream administered intravaginally five times a day for 5 days beginning 1h after infection significantly reduced HSV-2 replication beginning on day 1 of infection and prevented extravaginal disease when compared to animals treated with placebo. When resveratrol was tested at a concentration of 6.25% and 12.5% administered five times a day, 6.25% limited virus replication only on day 1 and delayed development of extravaginal disease by 1 day. However, 12.5% resveratrol inhibited HSV-2 replication beginning on day 1 and abolished extravaginal disease. If the number of applications per day was reduced to three for 5 days, 12.5% resveratrol inhibited HSV-2 replication only on day 1, while 19% resveratrol inhibited it throughout the 9-day assay period. When the animals with three treatments per day were examined for extravaginal disease, it was found that 12.5% resveratrol was ineffective when compared to placebo, while animals treated with 19% resveratrol did not exhibit extravaginal disease. When treatment was delayed 6h, 12.5% resveratrol did not inhibit HSV-2 replication or extravaginal lesion formation, but 19% resveratrol did. When resveratrol was used to treat vaginal HSV-1 infection, it was found that 12.5% resveratrol did not limit replication or prevent extravaginal lesion formation. In contrast, 19% resveratrol did significantly limit vaginal HSV-1 replication and reduced extravaginal lesion formation, but the latter was not significant. Mortality rates in placebo-treated animals was 37%, 6.25% resveratrol-treated animals was 40%, 12.5% resveratrol-treated animals was 24%, and 19% resveratrol-treated animals was 3%. Collectively, these results demonstrate that resveratrol cream inhibits or reduces HSV replication in the vagina of mice and limits extravaginal disease.
Docherty John J; Fu Ming Ming; Hah Jennifer M; Sweet Thomas J; Faith Seth A; Booth Tristan
Antiviral research
2005
2005-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.antiviral.2005.06.008" target="_blank" rel="noreferrer noopener">10.1016/j.antiviral.2005.06.008</a>
A block in glycoprotein processing correlates with small plaque morphology and virion targetting to cell-cell junctions for an oral and an anal strain of herpes simplex virus type-1.
*Protein Processing; Anal Canal/virology; Animals; Cercopithecus aethiops; Electron; Fluorescent Antibody Technique; Genetic Complementation Test; Herpesvirus 1; Human/genetics/isolation & purification/*physiology; Humans; Indirect; Intercellular Junctions/physiology/*virology; Kinetics; Microscopy; Mouth/virology; Post-Translational; Species Specificity; Vero Cells; Viral Envelope Proteins/*biosynthesis/metabolism; Viral Plaque Assay; Virion/*physiology
The characteristics of two clinical isolates of HSV-1 obtained from an oral (424) and an anal (490) lesion were compared with the highly passaged KOS strain. In contrast to KOS, the clinical isolates produced small plaques, were more cell-associated and the predominant viral glycoprotein species for gC and gD in infected cell lysates was the precursor, high mannose glycoform. Total virus production in Vero cells was equivalent for the three virus strains in one-step growths. Pulse-chase studies of glycoprotein C processing showed a reduction in rate at 7.5 h post infection and a significant block in processing at 10.5 h post infection for 424 and 490 but not KOS. Similar results were obtained for gD. The significant reduction in glycoprotein processing for 424 and 490 suggests a block in transport of viral glycoproteins or virions to and through the Golgi apparatus. Extracellular virions and the cell surface, prior to cell lysis, contained the processed gC glycoform suggesting a competent cellular glycan processing system. Upon co-infection of 424 or 490 with KOS or a gC- KOS strain, gC was processed to levels equivalent to KOS indicating that 424 and 490 are not inhibitory but that an activity(s) encoded by KOS facilitates maturation of gC from 424 and 490. Unlike KOS infected Vero cells, virion-containing vacuoles were observed in the cytoplasm at 12 h p.i. and extracellular virions were concentrated at cell-cell junctions of 424 or 490 infected cells but not in the perinuclear region. These results suggest that intracellular transport of viral glycoproteins and virions in 424 and 490 infected cells is different from KOS infected cells. The reduced level of viral glycoprotein maturation, virus release, cell surface presence and presence of virions at cell-cell junctions are consistent with small plaque production in tissue culture cells.
Dick J W; Rosenthal K S
Archives of virology
1995
1995
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/bf01323238" target="_blank" rel="noreferrer noopener">10.1007/bf01323238</a>
Subcellular localization and antiviral activity of carminic acid/poly r(A-U) combinations.
Antiviral Agents/*pharmacology; Carmine/*analogs & derivatives/pharmacokinetics/pharmacology; Cell Nucleolus/metabolism; Cells; Chromatin/metabolism; Cultured; Doxorubicin/pharmacology; Drug Combinations; Drug Synergism; Fluorescence; Humans; Interferon-beta/biosynthesis/physiology; Microscopy; Phase-Contrast; Poly A-U/*pharmacokinetics/*pharmacology; Vesicular stomatitis Indiana virus/drug effects/growth & development; Viral Plaque Assay
Carminic acid (CAR) enhances the antiviral activity of poly r(A-U) twelve-fold without increasing interferon induction, inactivating the vesicular stomatitis virus or inducing host cell cytotoxicity. Phase contrast photomicrographs of human foreskin fibroblasts (HSF) incubated with CAR alone, poly r(A-U) alone or with a CAR/poly r(A-U) combination illustrate that the CAR/poly r(A-U) combinations display altered subcellular distribution with the CAR being localized in the nucleoli and chromatin. Phase contrast and fluorescence photomicrographs of adriamycin (ADR)-treated and ADR/poly r(A-U)-treated HSF cells corroborate these findings. These results suggest that modulation of one or more nucleolar processes may be responsible for the enhanced antiviral activity.
Krabill K; Jamison J M; Gilloteaux J; Summers J L
Cell biology international
1993
1993-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/cbir.1993.1014" target="_blank" rel="noreferrer noopener">10.1006/cbir.1993.1014</a>