scholarly journals θ Defensins Protect Cells from Infection by Herpes Simplex Virus by Inhibiting Viral Adhesion and Entry

2004 ◽  
Vol 78 (10) ◽  
pp. 5147-5156 ◽  
Author(s):  
Bushra Yasin ◽  
Wei Wang ◽  
Mabel Pang ◽  
Natalia Cheshenko ◽  
Teresa Hong ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Nuclear Translocation ◽  
Temperature Shift ◽  
Virus Surface ◽  
Herpes Simplex Viruses ◽  
Viral Attachment ◽  
High Affinity ◽  
Simplex Virus ◽  
Hiv 1

ABSTRACT We tested the ability of 20 synthetic θ defensins to protect cells from infection by type 1 and type 2 herpes simplex viruses (HSV-1 and -2, respectively). The peptides included rhesus θ defensins (RTDs) 1 to 3, originally isolated from rhesus macaque leukocytes, and three peptides (retrocyclins 1 to 3) whose sequences were inferred from human θ-defensin (DEFT) pseudogenes. We also tested 14 retrocyclin analogues, including the retro, enantio, and retroenantio forms of retrocyclin 1. Retrocyclins 1 and 2 and RTD 3 protected cervical epithelial cells from infection by both HSV serotypes, but only retrocyclin 2 did so without causing cytotoxicity or requiring preincubation with the virus. Surface plasmon resonance studies revealed that retrocyclin 2 bound to immobilized HSV-2 glycoprotein B (gB2) with high affinity (Kd , 13.3 nM) and that it did not bind to enzymatically deglycosylated gB2. Temperature shift experiments indicated that retrocyclin 2 and human α defensins human neutrophil peptide 1 (HNP 1) to HNP 3 protected human cells from HSV-2 by different mechanisms. Retrocyclin 2 blocked viral attachment, and its addition during the binding or penetration phases of HSV-2 infection markedly diminished nuclear translocation of VP16 and expression of ICP4. In contrast, HNPs 1 to 3 had little effect on binding but reduced both VP16 transport and ICP4 expression if added during the postbinding (penetration) period. We recently reported that θ defensins are miniature lectins that bind gp120 of human immunodeficiency virus type 1 (HIV-1) with high affinity and inhibit the entry of R5 and X4 isolates of HIV-1. Given its small size (18 residues), minimal cytotoxicity, lack of activity against vaginal lactobacilli, and effectiveness against both HSV-2 and HIV-1, retrocyclin 2 provides an intriguing prototype for future topical microbicide development.

scholarly journals Herpes Simplex Virus Type 1 Induction of Persistent NF-κB Nuclear Translocation Increases the Efficiency of Virus Replication

Virology ◽  
1998 ◽  
Vol 247 (2) ◽  
pp. 212-222 ◽  
Author(s):  
Amit Patel ◽  
Julie Hanson ◽  
Tim I. McLean ◽  
Jennifer Olgiate ◽  
Melissa Hilton ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Replication ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Nuclear Translocation ◽  
Simplex Virus

scholarly journals Efficient Replication by Herpes Simplex Virus Type 1 Involves Activation of the IκB Kinase-IκB-p65 Pathway

2004 ◽  
Vol 78 (24) ◽  
pp. 13582-13590 ◽  
Author(s):  
D. Gregory ◽  
D. Hargett ◽  
D. Holmes ◽  
E. Money ◽  
S. L. Bachenheimer
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Infection ◽  
Virus Replication ◽  
Nuclear Translocation ◽  
Virus Yield ◽  
Iκb Kinase ◽  
Efficient Replication ◽  
Simplex Virus

ABSTRACT Infection by herpes simplex virus type 1 (HSV-1) induces a persistent nuclear translocation of NFκB. To identify upstream effectors of NFκB and their effect on virus replication, we employed mouse embryo fibroblast (MEF)-derived cell lines with deletions of either IKK1 or IKK2, the catalytic subunits of the IκB kinase (IKK) complex. Infected MEFs were assayed for virus yield, loss of IκBα, nuclear translocation of p65, and NFκB DNA-binding activity. Absence of either IKK1 or IKK2 resulted in an 86 to 94% loss of virus yield compared to that of normal MEFs, little or no loss of IκBα, and greatly reduced NFκB nuclear translocation. Consistent with reduced virus yield, accumulation of the late proteins VP16 and gC was severely depressed. Infection of normal MEFs, Hep2, or A549 cells with an adenovirus vector expressing a dominant-negative (DN) IκBα, followed by superinfection with HSV, resulted in a 98% drop in virus yield. These results indicate that the IKK-IκB-p65 pathway activates NFκB after virus infection. Analysis of NFκB activation and virus replication in control and double-stranded RNA-activated protein kinase-null MEFs indicated that this kinase plays no role in the NFκB activation pathway. Finally, in cells where NFκB was blocked because of DNIκB expression, HSV failed to suppress two markers of apoptosis, cell surface Annexin V staining and PARP cleavage. These results support a model in which activation of NFκB promotes efficient replication by HSV, at least in part by suppressing a host innate response to virus infection.

scholarly journals Characterization of Herpes Simplex Viruses Selected in Culture for Resistance to Penciclovir or Acyclovir

2001 ◽  
Vol 75 (4) ◽  
pp. 1761-1769 ◽  
Author(s):  
Robert T. Sarisky ◽  
Matthew R. Quail ◽  
Philip E. Clark ◽  
Tammy T. Nguyen ◽  
Wendy S. Halsey ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Sequence Similarity ◽  
Cross Resistance ◽  
Phenotypic Analysis ◽  
Herpes Simplex Viruses ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Penciclovir (PCV), an antiherpesvirus agent in the same class as acyclovir (ACV), is phosphorylated in herpes simplex virus (HSV)-infected cells by the viral thymidine kinase (TK). Resistance to ACV has been mapped to mutations within either the TK or the DNA polymerase gene. An identical activation pathway, the similarity in mode of action, and the invariant cross-resistance of TK-negative mutants argue that the mechanisms of resistance to PCV and ACV are likely to be analogous. A total of 48 HSV type 1 (HSV-1) and HSV-2 isolates were selected after passage in the presence of increasing concentrations of PCV or ACV in MRC-5 cells. Phenotypic analysis suggested these isolates were deficient in TK activity. Moreover, sequencing of the TK genes from ACV-selected mutants identified two homopolymeric G-C nucleotide stretches as putative hot spots, thereby confirming previous reports examining Acvr clinical isolates. Surprisingly, mutations identified in PCV-selected mutants were generally not in these regions but distributed throughout the TK gene and at similar frequencies of occurrence within A-T or G-C nucleotides, regardless of virus type. Furthermore, HSV-1 isolates selected in the presence of ACV commonly included frameshift mutations, while PCV-selected HSV-1 mutants contained mostly nonconservative amino acid changes. Data from this panel of laboratory isolates show that Pcvr mutants share cross-resistance and only limited sequence similarity with HSV mutants identified following ACV selection. Subtle differences between PCV and ACV in the interaction with viral TK or polymerase may account for the different spectra of genotypes observed for the two sets of mutants.

scholarly journals Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160

2017 ◽  
Vol 92 (2) ◽  
Author(s):  
Sachith Polpitiya Arachchige ◽  
Wyatt Henke ◽  
Ankita Pramanik ◽  
Maria Kalamvoki ◽  
Edward B. Stephens
Keyword(s):  
Human Immunodeficiency Virus ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Human Immunodeficiency Virus Type ◽  
Herpes Simplex Virus 1 ◽  
Immunodeficiency Virus ◽  
Simplex Virus ◽  
Hiv 1 ◽  
Hsv 1

ABSTRACTVirus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways.IMPORTANCEHIV-1 infection of humans results in AIDS, characterized by the loss of CD4+T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell.

Herpes simplex virus type 1-encoded glycoprotein C enhances coagulation factor VIIa activity on the virus

2004 ◽  
Vol 92 (11) ◽  
pp. 947-955 ◽  
Author(s):  
Michael Sutherland ◽  
Harvey Friedman ◽  
Edward Pryzdial
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Specific Antibody ◽  
Herpes Simplex Virus Type ◽  
Factor Viia ◽  
Virus Surface ◽  
Glycoprotein C ◽  
Simplex Virus

SummaryTissue factor (TF) is the blood coagulation initiator, whose cofactor function is required for physiological factor VIIa (FVIIa)-mediated activation of factor X (FX) to FXa. A previous study reported TF on herpes simplex virus type 1 (HSV1), but this explained only part of FVIIa-dependent FXa generation observed on the virus surface (Sutherland et al. (1997) Proc. Natl. Acad. Sci. USA. 94:13510-14). In the current study, we investigated the role of HSV1-encoded glycoprotein C (gC) in this process. Purified gC-deficient HSV1 facilitated several fold less FX activation by FVIIa than either wild type or gC-rescued strains.To confirm the implication of gC in FVIIa-dependent FX activation, purified soluble gC (sgC) enhanced FXa production in the absence of TF. sgC required FVIIa, calcium and anionic phospholipid to participate in FX activation, suggesting similarity to TF. When purified virus was combined with sgC, the sgC-dependent FXa generation was enhanced three orders of magnitude, suggesting synergy with an additional HSV1 component and explaining the relatively low activity of purified sgC compared to the viral counterpart. FX activation on gC-competent HSV1 was inhibited 20% by a gC-specific antibody, inhibited 40% by a TF-specific antibody, inhibited 65% by combining the gCand TF-specific antibodies, and nearly completely inhibited by the TF antibody alone on gC-deficient HSV-1. Cumulatively, these observations show that two pathways initiating FX activation function in parallel on the virus surface. In addition to the previously described TF-dependent pathway, HSV-1-encoded gC also enhances FXa generation, and like TF, requires FVIIa.

scholarly journals HSV-1/HSV-2 Infection-Related Cancers in Bantu Populations Driving HIV-1 Prevalence in Africa: Tracking the Origin of AIDS at the Onset of the 20th Century

2016 ◽  
Vol 9 (3) ◽  
pp. 815-825
Author(s):  
Jacqueline Le Goaster ◽  
Patrice Bouree ◽  
Franck N. El Sissy ◽  
Florence Phuong Bui ◽  
Johanna Pokossy Epee ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Sub Saharan Africa ◽  
Immunodeficiency Virus ◽  
Sub Saharan ◽  
Simplex Virus ◽  
Hiv 1 ◽  
Hsv 1

Introduction: At the onset of the 20th century, ancient clinical observations of cancer epidemics in Bantu populations of Sub-Saharan Africa were discovered. They were reported from 1914 to 1960, but remained unexplained. In 1983, in San Francisco, Calif., USA, cancer epidemics were related to infections by the human immunodeficiency virus type 1 (HIV-1) known as AIDS disease. Yet since 1996, it is known that HIV-1 strains are not the only ones involved. In Sub-Saharan Africa, recurrent orobuccal herpes simplex virus type 1 (HSV-1) and genital recurrent herpes simplex virus type 2 (HSV-2) appeared many times prior to infection by HIV-1. Case Reports: Data on these ancient medical observations regarding African cancer epidemics can today be referred to as the relationship between the unfortunate immune deficiency of herpes in Bantu populations and HIV-1 viral strains. For centuries, the Bantu populations dispersed in forests were living in close proximity to chimpanzees infected by simian immunodeficiency virus (SIV) and were exposed to SIV contamination which became HIV-1 in human beings. Presently, these unexplained Bantu cancer epidemics can be linked to the viral partnership of HSV-1/HSV-2 to HIV-1 strains. Conclusion: The key issue is now to prevent HSV-1/HSV-2 diseases related to HIV-1. An anti-herpes treatment administered early during childhood to Bantu populations will offer a mean of preventing herpes diseases related to HIV-1 infection and hence avoid cancer epidemics.

scholarly journals Performance of Two Commercial Glycoprotein G-Based Enzyme Immunoassays for Detecting Antibodies to Herpes Simplex Viruses 1 and 2 in Children and Young Adolescents

2002 ◽  
Vol 9 (5) ◽  
pp. 1124-1125 ◽  
Author(s):  
Charles T. Leach ◽  
Rhoda L. Ashley ◽  
Jacques Baillargeon ◽  
Hal B. Jenson
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Enzyme Linked Immunosorbent Assay ◽  
Aged Patients ◽  
Herpes Simplex Viruses ◽  
Glycoprotein G ◽  
Children And Young Adolescents ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT In 61 patients 1 to 14 years of age, the Gull/Meridian enzyme-linked immunosorbent assay (ELISA) had a sensitivity of 100% for herpes simplex virus type 1 (HSV-1) and specificities of 74% for HSV-1 and 48% for HSV-2. In 128 similarly aged patients, the HerpeSelect ELISA (Focus Technologies) showed sensitivities of 80% for HSV-1 and 88% for HSV-2, and specificities of 97% for HSV-1 and 100% for HSV-2.

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