scholarly journals Modified FGF4 Signal Peptide Inhibits Entry of Herpes Simplex Virus Type 1

2001 ◽  
Vol 75 (6) ◽  
pp. 2634-2645 ◽  
Author(s):  
Hermann Bultmann ◽  
James S. Busse ◽  
Curtis R. Brandt
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Signal Sequence ◽  
Host Cells ◽  
Virus Attachment ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Entry of herpes simplex virus type 1 (HSV-1) into host cells occurs through fusion of the viral envelope with the plasma membrane and involves complex and poorly understood interactions between several viral and cellular proteins. One strategy for dissecting the function of this fusion machine is through the use of specific inhibitors. We identified a peptide with antiviral activity that blocks HSV-1 infection at the entry stage and during cell-to-cell spreading. This peptide (called EB for “entry blocker”) consists of the FGF4 signal sequence with an RRKK tetramer at the amino terminus to improve solubility. The activity of EB depends exclusively but not canonically on the signal sequence. Inhibition of virus entry (hrR3) and plaque formation (KOS) strongly depend on virus concentrations and serum addition, with 50% inhibitory concentrations typically ranging from 1 to 10 μM. Blocking preadsorbed virus requires higher EB concentrations. Cytotoxic effects (trypan blue exclusion) are first noted at 50 μM EB in serum-free medium and at ≥200 μM in the presence of serum. EB does not affect gC-dependent mechanisms of virus attachment and does not block virus attachment at 4°C. Instead, EB directly interacts with virions and inactivates them irreversibly without, however, disrupting their physical integrity as judged by electron microscopy. At subvirucidal concentrations, EB changes the adhesive properties of virions, causing aggregation at high virus concentrations. This peptide may be a useful tool for studying viral entry mechanisms.

scholarly journals A Subcellular Quantitative Proteomic Analysis of Herpes Simplex Virus Type 1-Infected HEK 293T Cells

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4215 ◽  
Author(s):  
Wan ◽  
Wang ◽  
Chen ◽  
Zhu ◽  
Shang ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Proteomic Analysis ◽  
Coiled Coil ◽  
Host Cells ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus type 1 (HSV-1) is widespread double-stranded DNA (dsDNA) virus that establishes life-long latency and causes diverse severe symptoms. The mechanisms of HSV-1 infection and HSV-1’s interactions with various host cells have been studied and reviewed extensively. Type I interferons were secreted by host cells upon HSV infection and play a vital role in controlling virus proliferation. A few studies, however, have focused on HSV-1 infection without the presence of interferon (IFN) signaling. In this study, HEK 293T cells with low toll-like receptor (TLR) and stimulator of interferon genes protein (STING) expression were infected with HSV-1 and subjected to a quantitative proteomic analysis. By using a subcellular fractionation strategy and high-performance mass spectrometry, a total of 6607 host proteins were quantified, of which 498 proteins were differentially regulated. A bioinformatics analysis indicated that multiple signaling pathways might be involved in HSV-1 infection. A further functional study indicated the role of Interferon-induced transmembrane protein 3 (IFITM3), Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2), and Tripartite motif-containing protein 27 (TRIM27) in inhibiting viral DNA replication and proliferation. Our data provide a global view of host responses to HSV-1 infection in HEK 293T cells and identify the proteins involved in the HSV-1 infection process.

scholarly journals Herpes Simplex Virus Type 1 Evades the Effects of Antibody and Complement In Vivo

2002 ◽  
Vol 76 (18) ◽  
pp. 9232-9241 ◽  
Author(s):  
John M. Lubinski ◽  
Ming Jiang ◽  
Lauren Hook ◽  
Yueh Chang ◽  
Chad Sarver ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Immune Evasion ◽  
Herpes Simplex Virus Type ◽  
Complement Components ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) encodes a complement-interacting glycoprotein, gC, and an immunoglobulin G (IgG) Fc binding glycoprotein, gE, that mediate immune evasion by affecting multiple aspects of innate and acquired immunity, including interfering with complement components C1q, C3, C5, and properdin and blocking antibody-dependent cellular cytotoxicity. Previous studies evaluated the individual contributions of gC and gE to immune evasion. Experiments in a murine model that examines the combined effects of gC and gE immune evasion on pathogenesis are now reported. Virulence of wild-type HSV-1 is compared with mutant viruses defective in gC-mediated C3 binding, gE-mediated IgG Fc binding, or both immune evasion activities. Eliminating both activities greatly increased susceptibility of HSV-1 to antibody and complement neutralization in vitro and markedly reduced virulence in vivo as measured by disease scores, virus titers, and mortality. Studies with C3 knockout mice indicated that other activities attributed to these glycoproteins, such as gC-mediated virus attachment to heparan sulfate or gE-mediated cell-to-cell spread, do not account for the reduced virulence of mutant viruses. The results support the importance of gC and gE immune evasion in vivo and suggest potential new targets for prevention and treatment of HSV disease.

scholarly journals The UL12.5 Gene Product of Herpes Simplex Virus Type 1 Exhibits Nuclease and Strand Exchange Activities but Does Not Localize to the Nucleus

2004 ◽  
Vol 78 (9) ◽  
pp. 4599-4608 ◽  
Author(s):  
Nina Bacher Reuven ◽  
Susumu Antoku ◽  
Sandra K. Weller
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Intracellular Localization ◽  
Strand Exchange ◽  
Null Mutant ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The herpes simplex virus type 1 (HSV-1) alkaline nuclease, encoded by the UL12 gene, plays an important role in HSV-1 replication, as a null mutant of UL12 displays a severe growth defect. Although the precise in vivo role of UL12 has not yet been determined, several in vitro activities have been identified for the protein, including endo- and exonuclease activities, interaction with the HSV-1 single-stranded DNA binding protein ICP8, and an ability to promote strand exchange in conjunction with ICP8. In this study, we examined a naturally occurring N-terminally truncated version of UL12 called UL12.5. Previous studies showing that UL12.5 exhibits nuclease activity but is unable to complement a UL12 null virus posed a dilemma and suggested that UL12.5 may lack a critical activity possessed by the full-length protein, UL12. We constructed a recombinant baculovirus capable of expressing UL12.5 and purified soluble UL12.5 from infected insect cells. The purified UL12.5 exhibited both endo- and exonuclease activities but was less active than UL12. Like UL12, UL12.5 could mediate strand exchange with ICP8 and could also be coimmunoprecipitated with ICP8. The primary difference between the two proteins was in their intracellular localization, with UL12 localizing to the nucleus and UL12.5 remaining in the cytoplasm. We mapped a nuclear localization signal to the N terminus of UL12, the domain absent from UL12.5. In addition, when UL12.5 was overexpressed so that some of the enzyme leaked into the nucleus, it was able to partially complement the UL12 null mutant.

scholarly journals Entry of Herpes Simplex Virus Type 1 into Primary Sensory Neurons In Vitro Is Mediated by Nectin-1/HveC

2003 ◽  
Vol 77 (5) ◽  
pp. 3307-3311 ◽  
Author(s):  
Sarah M. Richart ◽  
Scott A. Simpson ◽  
Claude Krummenacher ◽  
J. Charles Whitbeck ◽  
Lewis I. Pizer ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sensory Neurons ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Primary Cultures ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Primary cultures of rat and mouse sensory neurons were used to study the entry of herpes simplex virus type 1 (HSV-1). Soluble, truncated nectin-1 but not HveA prevented viral entry. Antibodies against nectin-1 also blocked infection of rat neurons. These results indicate that nectin-1 is the primary receptor for HSV-1 infection of sensory neurons.

scholarly journals Pathological processes of immunological decontamination of herpes simplex virus type 1 from the cornea

2020 ◽  
pp. 4-11
Author(s):  
Т.З. Керимов ◽  
В.П. Соболев ◽  
М.А. Соболева ◽  
Н.А. Гаврилова ◽  
С.А. Борзенок
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Herpes Virus ◽  
Toll Like Receptors ◽  
Herpès Virus ◽  
Simplex Virus ◽  
Hsv 1

В обзоре представлено описание патофизиологических механизмов герпесвирусной инфекции. Согласно данным медицинской статистики, вирусом простого герпеса 1 типа инфицировано большинство населения планеты. В развивающихся странах данный вирус является ведущей инфекционной причиной поражения роговицы. Также вирусу простого герпеса 1 типа отводится роль одного из факторов, приводящих к отторжению трансплантата роговицы. Вышеописанные патологические явления сопряжены с перестройкой клеточных систем в ответ на вирусное воздействие. Недавние открытия в данной области обнаружили значительный вклад трансмембранных и эндосомальных Toll-подобных рецепторов во врожденный противовирусный клеточный ответ. Показано, что эндосомальные Toll-подобные рецепторы 3 типа экспрессируются в кератоцитах только после их фенотипического перехода в фибробласты. Данная трансформация обычно происходит в результате механических и патогенных воздействий на роговицу. Изменение рецепторного состава клеток в ответ на герпесвирусную инвазию вызывает выработку интерферонов 1 типа - интерферона-альфа, интерферона-бета, и синтезу провоспалительных цитокинов, что приводит к вирусной деконтаминации. This review describes pathophysiological mechanisms of herpes virus infection in cornea cells. It has been previously reported that herpes simplex virus type 1 (HSV-1) infects most of the world’s population. In developing countries, HSV-1 is the leading infectious cause of corneal damage. Also, herpes simplex virus type 1 was assigned the role of one of the factors leading to rejection of the corneal transplant. These pathological phenomena are associated with restructuring of cellular systems in response to viral exposure. Recent discoveries have revealed a significant contribution of transmembrane and endosomal Toll-like receptors to the innate antiviral cell response. It is well known that endosomal Toll-like receptors-3 are expressed in keratocytes only after their phenotypic transformation to fibroblasts. This transformation usually occurs as a result of mechanical or infectious impact on the cornea. Changes in the receptor composition of cells as a response to herpes virus invasion is the main cause of type 1 interferons (interferon-alpha and interferon-beta) production and expression of proinflammatory cytokines, which leads to viral decontamination.

scholarly journals Replication of ICP0-Null Mutant Herpes Simplex Virus Type 1 Is Restricted by both PML and Sp100

2007 ◽  
Vol 82 (6) ◽  
pp. 2661-2672 ◽  
Author(s):  
Roger D. Everett ◽  
Carlos Parada ◽  
Philippe Gripon ◽  
Hüseyin Sirma ◽  
Anne Orr
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Human Fibroblasts ◽  
Null Mutant ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) mutants that fail to express the viral immediate-early protein ICP0 have a pronounced defect in viral gene expression and plaque formation in limited-passage human fibroblasts. ICP0 is a RING finger E3 ubiquitin ligase that induces the degradation of several cellular proteins. PML, the organizer of cellular nuclear substructures known as PML nuclear bodies or ND10, is one of the most notable proteins that is targeted by ICP0. Depletion of PML from human fibroblasts increases ICP0-null mutant HSV-1 gene expression, but not to wild-type levels. In this study, we report that depletion of Sp100, another major ND10 protein, results in a similar increase in ICP0-null mutant gene expression and that simultaneous depletion of both proteins complements the mutant virus to a greater degree. Although chromatin assembly and modification undoubtedly play major roles in the regulation of HSV-1 infection, we found that inhibition of histone deacetylase activity with trichostatin A was unable to complement the defect of ICP0-null mutant HSV-1 in either normal or PML-depleted human fibroblasts. These data lend further weight to the hypothesis that ND10 play an important role in the regulation of HSV-1 gene expression.

Sign in / Sign up

Export Citation Format

Share Document