scholarly journals Terminally Repeated Sequences on a Herpesvirus Genome Are Deleted following Circularization but Are Reconstituted by Duplication during Cleavage and Packaging of Concatemeric DNA

2002 ◽  
Vol 76 (4) ◽  
pp. 2009-2013 ◽  
Author(s):  
Daniel E. Nixon ◽  
Michael A. McVoy
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Guinea Pig ◽  
Terminal Repeat ◽  
Type I ◽  
Type Ii ◽  
Guinea Pig Cytomegalovirus ◽  
Terminal Repeats ◽  
Simplex Virus

ABSTRACT The mechanisms underlying cleavage of herpesvirus genomes from replicative concatemers are unknown. Evidence from herpes simplex virus type 1 suggests that cleavage occurs by a nonduplicative process; however, additional evidence suggests that terminal repeats may also be duplicated during the cleavage process. This issue has been difficult to resolve due to the variable numbers of reiterated terminal repeats that the herpes simplex virus type 1 genome can contain. Guinea pig cytomegalovirus is a herpesvirus with a simple terminal repeat arrangement that defines two genome types. Type II genomes have a single copy of a 1-kb terminal repeat at both their left and right termini, whereas type I genomes have only one copy at their left termini and lack the repeat at their right termini. In a previous study, we constructed a recombinant guinea pig cytomegalovirus in which certain cis elements were disrupted such that only type II genomes were produced. Here we show that double repeats that are formed by circularization of infecting genomes are rapidly converted to single repeats, such that the junctions between genomes within replicative concatemers formed late in infection almost exclusively contain single copies of the terminal repeat. Therefore, for the recombinant virus, each cleavage event begins with a single repeat within a concatemer yet produces two repeats, one at each of the resulting termini, demonstrating that terminal repeat duplication occurs in conjunction with cleavage. For wild-type guinea pig cytomegalovirus, the formation of type I genomes further suggests that cleavage can also occur by a nonduplicative process and that duplicative and nonduplicative cleavage can occur concurrently. Other herpesviruses having terminal repeats, such as the herpes simplex viruses and human cytomegalovirus, may also utilize repeat duplication and deletion; however, the biological importance of these events remains unknown.

scholarly journals Bioluminescence Imaging Reveals Systemic Dissemination of Herpes Simplex Virus Type 1 in the Absence of Interferon Receptors

2003 ◽  
Vol 77 (20) ◽  
pp. 11082-11093 ◽  
Author(s):  
Gary D. Luker ◽  
Julie L. Prior ◽  
Jiling Song ◽  
Christina M. Pica ◽  
David A. Leib
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
Bioluminescence Imaging ◽  
Type I ◽  
Type Ii ◽  
Systemic Dissemination ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) can produce disseminated, systemic infection in neonates and patients with AIDS or other immunocompromising diseases, resulting in significant morbidity and mortality in spite of antiviral therapy. Components of host immunity that normally limit HSV-1 to localized epithelial and neuronal infection remain incompletely defined. We used in vivo bioluminescence imaging to determine effects of type I and II interferons (IFNs) on replication and tropism of HSV-1 infection in mice with genetic deficiency of type I, type II, or both type I and II IFN receptors. Following footpad or ocular infection of mice lacking type I IFN receptors, HSV-1 spread to parenchymal organs, including lung, liver, spleen, and regional lymph nodes, but mice survived. Deletion of type I and II IFN receptors produced quantitatively greatest and most widespread dissemination of virus to visceral organs and the nervous system, and these mice invariably died after ocular or footpad infection. Type II receptor knockout and wild-type mice had comparable viral replication and localization, with no systemic spread of HSV-1 or lethality. Therefore, while isolated deficiency of type II IFN receptors did not affect pathogenesis, loss of these receptors in combination with genetic deletion of type I receptors had a profound effect on susceptibility to HSV-1. These data demonstrate different effects of type I and II IFNs in limiting systemic dissemination of HSV-1 and further validate the use of bioluminescence imaging for studies of viral pathogenesis.

Multiple sclerosis: reduced proportion of circulating plasmacytoid dendritic cells expressing BDCA-2 and BDCA-4 and reduced production of IL-6 and IL-10 in response to herpes simplex virus type 1

2008 ◽  
Vol 14 (9) ◽  
pp. 1199-1207 ◽  
Author(s):  
A Sanna ◽  
YM Huang ◽  
G Arru ◽  
ML Fois ◽  
H Link ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Cytokine Production ◽  
Type I ◽  
Simplex Virus ◽  
Hsv 1

Objective We hypothesized that autoaggressive immune responses observed in multiple sclerosis (MS) could be associated with an imbalance in proportion of immune cell subsets and in cytokine production in response to infection, including viruses. Methods We collected blood mononuclear cells (MNC) from 23 patients with MS and 23 sex- and age-matched healthy controls (HC) from the island of Sardinia, Italy, where the prevalence of MS is extraordinarily high. Using flow cytometry, we studied MNC for expression of blood dendritic cell antigens (BDCA)-2 and BDCA-4 surface markers reflecting the proportion of plasmacytoid dendritic cells (pDC) that produce type I interferons (IFNs) after virus challenge and promote Th2/anti-inflammtory cytokine production. In parallel, pro-inflammatory (interleukin [IL]-2, IL-12, IFN-γ), anti-inflammatory (IL-4, IL-10), and immuno-regulatory/pleiotropic cytokines (type I IFNs including IFN-α and β, IL-6) were measured before and after an in vitro exposure to herpes simplex virus type 1 (HSV-1). Results The subset of lineage negative (lin−), BDCA-2+ cells was lower in patients with MS compared with HC (0.08 ± 0.02% vs 0.24 ± 0.02%; P < 0.001). A similar pattern was observed for lin−BDCA-4+ cells (0.08 ± 0.02% vs 0.17% ± 0.03; P < 0.01). Spontaneous productions of IL-6 (45 ± 10 pg/mL vs 140 ± 26 pg/mL; P < 0.01) and IL-10 (17 ± 0.4 pg/mL vs 21 ± 1 pg/mL; P < 0.05) by MNC were lower in patients with MS compared with HC. Spontaneous production of IL-6 (6.5 ± 0.15 pg/mL vs 21 ± 5 pg/mL; P < 0.01 and IL-10 (11 ± 1 pg/mL vs 14 ± 3 pg/mL; P < 0.05) by pDC was also lower in patients with MS compared with HC. Exposure of MNC to HSV-1 showed, in both patients with MS and HC, increased production of IFN-α, IL-6, and IL-10 but decreased production of IL-4. In response to HSV-1 exposure, productions of IL-6 (165 ± 28 pg/mL vs 325 ± 35 pg/mL; P < 0.01) and IL-10 (27 ± 3 vs 33 ± 3 P < 0.05) by MNC as well as by pDC (IL-6: 28 ± 7 vs 39 ± 12 P < 0.05; IL-10: 14 ± 1 vs 16 ± 3 P < 0.05) were lower in patients with MS compared with HC. Conclusion The results implicate a new evidence for altered immune cells and reduced immune responses in response to viral challenge in MS.

Participation of Type I Interferon in the Decreased Virulence of the UL13 Gene-Deleted Mutant of Herpes Simplex Virus Type 1

2001 ◽  
Vol 21 (5) ◽  
pp. 279-285 ◽  
Author(s):  
Taiichiro Shibaki ◽  
Tatsuo Suzutani ◽  
Itsuro Yoshida ◽  
Masahiro Ogasawara ◽  
Masanobu Azuma
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Type I Interferon ◽  
Type I ◽  
Simplex Virus

scholarly journals Brain immune cells undergo cGAS/STING-dependent apoptosis during herpes simplex virus type 1 infection to limit type I IFN production

2021 ◽  
Vol 131 (1) ◽  
Author(s):  
Line S. Reinert ◽  
Ahmad S. Rashidi ◽  
Diana N. Tran ◽  
Georgios Katzilieris-Petras ◽  
Astrid K. Hvidt ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Immune Cells ◽  
Herpes Simplex Virus Type ◽  
Type I ◽  
Type I Ifn ◽  
Simplex Virus

scholarly journals Herpes Simplex Virus Type 1 Infection Disturbs the Mitochondrial Network, Leading to Type I Interferon Production through the RNA Polymerase III/RIG-I Pathway

mBio ◽  
2021 ◽  
Author(s):  
Noémie Berry ◽  
Rodolphe Suspène ◽  
Vincent Caval ◽  
Pierre Khalfi ◽  
Guillaume Beauclair ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Type I Interferon ◽  
Rna Polymerase Iii ◽  
Type I ◽  
Interferon Production ◽  
Mitochondrial Network ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus

Herpes simplex virus 1 (HSV-1) impairs the mitochondrial network through the viral protein UL12.5. This leads to the fusion of mitochondria and simultaneous release of mitochondrial DNA (mtDNA) in a mouse model.

scholarly journals An N-Terminal Domain of Herpes Simplex Virus Type I gE Is Capable of Forming Stable Complexes with gI

2001 ◽  
Vol 75 (23) ◽  
pp. 11897-11901 ◽  
Author(s):  
Syed Monem Rizvi ◽  
Malini Raghavan
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Domain Boundary ◽  
Stable Complex ◽  
Type I ◽  
Terminal Domain ◽  
Simplex Virus

ABSTRACT Using limited proteolytic analyses, we show that gE present in soluble herpes simplex virus type 1 gE-gI complexes is cleaved into a C-terminal (CgE) and an N-terminal (NgE) domain. The domain boundary is in the vicinity of residue 188 of mature gE. NgE, but not CgE, forms a stable complex with soluble gI.

scholarly journals Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion

mBio ◽  
2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Ren Song ◽  
Orkide O. Koyuncu ◽  
Todd M. Greco ◽  
Benjamin A. Diner ◽  
Ileana M. Cristea ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Body ◽  
Type I ◽  
Dependent Manner ◽  
Type Ii ◽  
Long Distance ◽  
Peripheral Tissues ◽  
Ifn Γ ◽  
Simplex Virus

ABSTRACT Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS). Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs). The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-β) or gamma interferon (IFN-γ) significantly diminished the number of herpes simplex virus 1 (HSV-1) and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-β induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFN-γ induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN-γ, but not those induced by IFN-β. Proteomic analysis of IFN-β- or IFN-γ-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-γ, IFN-β induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion. IMPORTANCE Neurons are highly polarized cells with long axonal processes that connect to distant targets. PNS axons that innervate peripheral tissues are exposed to various situations that follow infection, inflammation, and damage of the tissue. After viral infection in the periphery, axons represent potential front-line barriers to PNS infection and damage. Indeed, most viral infections do not spread to the PNS, yet the mechanisms responsible are not well studied. We devised an experimental system to study how axons respond to inflammatory cytokines that would be produced by infected tissues. We found that axons respond differentially to type I and type II interferons. The response to type I interferon (IFN-β) is a rapid axon-only response. The response to type II interferon (IFN-γ) involves long-distance signaling to the PNS cell body. These responses to two interferons erect an efficient and rapid barrier to PNS infection.

scholarly journals Drosophila P element-enhanced transfection in mammalian cells.

1985 ◽  
Vol 5 (4) ◽  
pp. 898-901 ◽  
Author(s):  
D W Clough ◽  
H M Lepinske ◽  
R L Davidson ◽  
R V Storti
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Gene Transfer ◽  
Thymidine Kinase ◽  
Herpes Simplex Virus Type ◽  
Mammalian Cells ◽  
P Element ◽  
Terminal Repeats ◽  
Simplex Virus

We constructed a gene transfer vector containing the herpes simplex virus type 1 thymidine kinase (TK) gene flanked by Drosophila P element terminal repeats (W. R. Engels, Annu. Rev. Genet. 17:315-344). This vector was introduced into mouse LTK- cells and enhanced the frequency of stable transformation to the TK+ phenotype by approximately 50-fold relative to a similar plasmid lacking the P element terminal repeats.

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