scholarly journals Viperin has species-specific roles in response to herpes simplex virus infection

2021 ◽  
Vol 102 (8) ◽  
Author(s):  
Yeu-Yang Tseng ◽  
Anjali Gowripalan ◽  
Sarah N. Croft ◽  
Stewart A. Smith ◽  
Karla J. Helbig ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Specific Activity ◽  
Viral Gene ◽  
Cell Type ◽  
Primary Mouse ◽  
Mouse Cells ◽  
Species Specific ◽  
Simplex Virus ◽  
Hsv 1

Viperin is a gene with a broad spectrum of antiviral functions and various mechanisms of action. The role of viperin in herpes simplex virus type 1 (HSV-1) infection is unclear, with conflicting data in the literature that is derived from a single human cell type. We have addressed this gap by investigating viperin during HSV-1 infection in several cell types, spanning species and including immortalized, non-immortalized and primary cells. We demonstrate that viperin upregulation by HSV-1 infection is cell-type-specific, with mouse cells typically showing greater increases compared with those of human origin. Further, overexpression and knockout of mouse, but not human viperin significantly impedes and increases HSV-1 replication, respectively. In primary mouse fibroblasts, viperin upregulation by infection requires viral gene transcription and occurs in a predominantly IFN-independent manner. Further we identify the N-terminal domain of viperin as being required for the anti-HSV-1 activity. Interestingly, this is the region of viperin that differs most between mouse and human, which may explain the apparent species-specific activity against HSV-1. Finally, we show that HSV-1 virion host shutoff (vhs) protein is a key viral factor that antagonises viperin in mouse cells. We conclude that viperin can be upregulated by HSV-1 in mouse and human cells, and that mouse viperin has anti-HSV-1 activity.

scholarly journals PrPc Expression Influences the Establishment of Herpes Simplex Virus Type 1 Latency

2002 ◽  
Vol 76 (5) ◽  
pp. 2498-2509 ◽  
Author(s):  
Alana M. Thackray ◽  
Raymond Bujdoso
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Copper Metabolism ◽  
Normal Function ◽  
Viral Gene ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT PrPc is a glycophosphatidylinositol-linked cell-surface protein expressed principally by neural tissue. The normal function of this protein is unestablished, although a role in either transmembrane signaling, cell-cell adhesion, or copper metabolism has been proposed. In this study we have investigated the effect of the neurotropic virus herpes simplex virus type 1 (HSV-1) in strains of mice which express different levels of PrPc. Viral gene expression under the control of the HSV-1 early promoter IE110, detected either by in situ hybridization for RNA transcripts or by β-galactosidase (β-Gal) activity from an inserted lacZ gene, showed that the magnitude of HSV replication was retarded in PrP−/− mice. This was reflected in the lower level of acute viral titers in tissues from these virus-inoculated mice. However, HSV-inoculated PrP−/− mice contained higher levels of latent virus in both peripheral and central nervous tissue than those seen in mice which express PrPc. Our observations show that lack of PrPc expression favors the establishment of HSV latency whereas HSV replication proceeds more efficiently in neuronal tissue that expresses this protein. The data further suggest that PrPc may be involved in a metabolic pathway that culminates in apoptosis of neurons that have been infected by neurotropic viruses.

scholarly journals Cellular Protein WDR11 Interacts with Specific Herpes Simplex Virus Proteins at thetrans-Golgi Network To Promote Virus Replication

2015 ◽  
Vol 89 (19) ◽  
pp. 9841-9852 ◽  
Author(s):  
Kathryne E. Taylor ◽  
Karen L. Mossman
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Replication ◽  
Cellular Protein ◽  
Viral Gene ◽  
Late Gene Expression ◽  
Simplex Virus ◽  
Golgi Network ◽  
Hsv 1

ABSTRACTIt has recently been proposed that the herpes simplex virus (HSV) protein ICP0 has cytoplasmic roles in blocking antiviral signaling and in promoting viral replication in addition to its well-known proteasome-dependent functions in the nucleus. However, the mechanisms through which it produces these effects remain unclear. While investigating this further, we identified a novel cytoplasmic interaction between ICP0 and the poorly characterized cellular protein WDR11. During an HSV infection, WDR11 undergoes a dramatic change in localization at late times in the viral replication cycle, moving from defined perinuclear structures to a dispersed cytoplasmic distribution. While this relocation was not observed during infection with viruses other than HSV-1 and correlated with efficient HSV-1 replication, the redistribution was found to occur independently of ICP0 expression, instead requiring viral late gene expression. We demonstrate for the first time that WDR11 is localized to thetrans-Golgi network (TGN), where it interacts specifically with some, but not all, HSV virion components, in addition to ICP0. Knockdown of WDR11 in cultured human cells resulted in a modest but consistent decrease in yields of both wild-type and ICP0-null viruses, in the supernatant and cell-associated fractions, without affecting viral gene expression. Although further study is required, we propose that WDR11 participates in viral assembly and/or secondary envelopment.IMPORTANCEWhile the TGN has been proposed to be the major site of HSV-1 secondary envelopment, this process is incompletely understood, and in particular, the role of cellular TGN components in this pathway is unknown. Additionally, little is known about the cellular functions of WDR11, although the disruption of this protein has been implicated in multiple human diseases. Therefore, our finding that WDR11 is a TGN-resident protein that interacts with specific viral proteins to enhance viral yields improves both our understanding of basic cellular biology as well as how this protein is co-opted by HSV.

scholarly journals Species-Specific Deamidation of RIG-I Reveals Collaborative Action between Viral and Cellular Deamidases in HSV-1 Lytic Replication

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Huichao Huang ◽  
Jun Zhao ◽  
Ting-Yu Wang ◽  
Shu Zhang ◽  
Yuzheng Zhou ◽  
...  
Keyword(s):  
Immune Response ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Defense ◽  
Immune Evasion ◽  
Herpes Simplex Virus 1 ◽  
Species Specific ◽  
Simplex Virus ◽  
Phosphoribosylpyrophosphate Amidotransferase ◽  
Hsv 1

ABSTRACT Retinoic acid-inducible gene I (RIG-I) is a sensor that recognizes cytosolic double-stranded RNA derived from microbes to induce host immune response. Viruses, such as herpesviruses, deploy diverse mechanisms to derail RIG-I-dependent innate immune defense. In this study, we discovered that mouse RIG-I is intrinsically resistant to deamidation and evasion by herpes simplex virus 1 (HSV-1). Comparative studies involving human and mouse RIG-I indicate that N495 of human RIG-I dictates species-specific deamidation by HSV-1 UL37. Remarkably, deamidation of the other site, N549, hinges on that of N495, and it is catalyzed by cellular phosphoribosylpyrophosphate amidotransferase (PPAT). Specifically, deamidation of N495 enables RIG-I to interact with PPAT, leading to subsequent deamidation of N549. Collaboration between UL37 and PPAT is required for HSV-1 to evade RIG-I-mediated antiviral immune response. This work identifies an immune regulatory role of PPAT in innate host defense and establishes a sequential deamidation event catalyzed by distinct deamidases in immune evasion. IMPORTANCE Herpesviruses are ubiquitous pathogens in human and establish lifelong persistence despite host immunity. The ability to evade host immune response is pivotal for viral persistence and pathogenesis. In this study, we investigated the evasion, mediated by deamidation, of species-specific RIG-I by herpes simplex virus 1 (HSV-1). Our findings uncovered a collaborative and sequential action between viral deamidase UL37 and a cellular glutamine amidotransferase, phosphoribosylpyrophosphate amidotransferase (PPAT), to inactivate RIG-I and mute antiviral gene expression. PPAT catalyzes the rate-limiting step of the de novo purine synthesis pathway. This work describes a new function of cellular metabolic enzymes in host defense and viral immune evasion.

Chicken ovalbumin gene fused to a herpes simplex virus alpha promoter and linked to a thymidine kinase gene is regulated like a viral gene

1982 ◽  
Vol 2 (3) ◽  
pp. 233-240
Author(s):  
L E Post ◽  
B Norrild ◽  
T Simpson ◽  
B Roizman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Extracellular Fluid ◽  
Regulatory Elements ◽  
Viral Gene ◽  
Herpes Simplex Virus 1 ◽  
Kinase Gene ◽  
Covalently Linked ◽  
Simplex Virus ◽  
Hsv 1

We are describing a system for the introduction, selection, and expression of eucaryotic genes in higher eucaryotic cells. The carrier consisted of the herpes simplex virus 1 (HSV-1) tk gene covalently linked to an HSV-1 alpha promoter directed away from the tk gene. In this study we fused to the alpha promoter the 5' transcribed noncoding sequences and the coding sequences of the chicken oviduct ovalbumin gene. Cells converted to the TK+ phenotype with this chimeric fragment produced an ovalbumin precursor which was processed and secreted into the extracellular fluid. The ovalbumin gene utilized the HSV-1 alpha promoter and was regulated as a viral gene inasmuch as inversion of the genomic DNA relative to the alpha promoter resulted in no ovalbumin synthesis, and production of ovalbumin was enhanced after superinfection with HSV-1. Synthesis of ovalbumin was not detected when cDNA was linked to the HSV-1 alpha promoter. The carrier system described in this study is suitable for introduction, selection, and expression of eucaryotic genes whose natural promoter is either weak or requires the presence of regulatory elements which may be absent from undifferentiated cells in culture.

scholarly journals Towards an Understanding of the Herpes Simplex Virus Type 1 Latency-Reactivation Cycle

2010 ◽  
Vol 2010 ◽  
pp. 1-18 ◽  
Author(s):  
Guey-Chuen Perng ◽  
Clinton Jones
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Productive Infection ◽  
Viral Gene ◽  
Trigeminal Ganglia ◽  
Simplex Virus ◽  
Hsv 1

Infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system. Recurrent ocular shedding can lead to corneal scarring and vision loss making HSV-1 a leading cause of corneal blindness due to an infectious agent. The primary site of HSV-1 latency is sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission and recurrent disease. During latency, the latency-associated transcript (LAT) is abundantly expressed. LAT expression is important for the latency-reactivation cycle in animal models, in part, because it inhibits apoptosis, viral gene expression, and productive infection. A novel transcript within LAT coding sequences (AL3) and small nonprotein coding RNAs are also expressed in trigeminal ganglia of latently infected mice. In this review, an update of viral factors that are expressed during latency and their potential roles in regulating the latency-reactivation cycle is discussed.

scholarly journals Latency-Associated Transcript (LAT) Exon 1 Controls Herpes Simplex Virus Species-Specific Phenotypes: Reactivation in the Guinea Pig Genital Model and Neuron Subtype-Specific Latent Expression of LAT

2009 ◽  
Vol 83 (19) ◽  
pp. 10007-10015 ◽  
Author(s):  
Andrea S. Bertke ◽  
Amita Patel ◽  
Yumi Imai ◽  
Kathleen Apakupakul ◽  
Todd P. Margolis ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Guinea Pig ◽  
Splice Site ◽  
Wild Type ◽  
Intron Splice ◽  
Exon 1 ◽  
Species Specific ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus 1 (HSV-1) and HSV-2 cause similar acute infections but differ in their abilities to reactivate from trigeminal and lumbosacral dorsal root ganglia. During latency, HSV-1 and HSV-2 also preferentially express their latency-associated transcripts (LATs) in different sensory neuronal subtypes that are positive for A5 and KH10 markers, respectively. Chimeric virus studies showed that LAT region sequences influence both of these viral species-specific phenotypes. To further map the LAT region sequences responsible for these phenotypes, we constructed the chimeric virus HSV2-LAT-E1, in which exon 1 (from the LAT TATA to the intron splice site) was replaced by the corresponding sequence from HSV-1 LAT. In intravaginally infected guinea pigs, HSV2-LAT-E1 reactivated inefficiently relative to the efficiency of its rescuant and wild-type HSV-2, but it yielded similar levels of viral DNA, LAT, and ICP0 during acute and latent infection. HSV2-LAT-E1 preferentially expressed the LAT in A5+ neurons (as does HSV-1), while the chimeric viruses HSV2-LAT-P1 (LAT promoter swap) and HSV2-LAT-S1 (LAT sequence swap downstream of the promoter) exhibited neuron subtype-specific latent LAT expression phenotypes more similar to that of HSV-2 than that of HSV-1. Rescuant viruses displayed the wild-type HSV-2 phenotypes of efficient reactivation in the guinea pig genital model and a tendency to express LAT in KH10+ neurons. The region that is critical for HSV species-specific differences in latency and reactivation thus lies between the LAT TATA and the intron splice site, and minor differences in the 5′ ends of chimeric sequences in HSV2-LAT-E1 and HSV2-LAT-S1 point to sequences immediately downstream of the LAT TATA.

scholarly journals Regulation of viral gene expression by the herpes simplex virus 1 UL24 protein (HSV-1 UL24 inhibits accumulation of viral transcripts)

Virology ◽  
2016 ◽  
Vol 495 ◽  
pp. 148-160 ◽  
Author(s):  
Carolina Sanabria-Solano ◽  
Carmen Elena Gonzalez ◽  
Nicolas Richerioux ◽  
Luc Bertrand ◽  
Slimane Dridi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

scholarly journals The latency-associated transcript locus of herpes simplex virus 1 is a virulence determinant in human skin

2020 ◽  
Vol 16 (12) ◽  
pp. e1009166
Author(s):  
Emilia A. H. Vanni ◽  
Joseph W. Foley ◽  
Andrew J. Davison ◽  
Marvin Sommer ◽  
Dongmei Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Human Skin ◽  
Lytic Infection ◽  
Growth Defect ◽  
Viral Gene ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus 1 (HSV-1) infects skin and mucosal epithelial cells and then travels along axons to establish latency in the neurones of sensory ganglia. Although viral gene expression is restricted during latency, the latency-associated transcript (LAT) locus encodes many RNAs, including a 2 kb intron known as the hallmark of HSV-1 latency. Here, we studied HSV-1 infection and the role of the LAT locus in human skin xenografts in vivo and in cultured explants. We sequenced the genomes of our stock of HSV-1 strain 17syn+ and seven derived viruses and found nonsynonymous mutations in many viral proteins that had no impact on skin infection. In contrast, deletions in the LAT locus severely impaired HSV-1 replication and lesion formation in skin. However, skin replication was not affected by impaired intron splicing. Moreover, although the LAT locus has been implicated in regulating gene expression in neurones, we observed only small changes in transcript levels that were unrelated to the growth defect in skin, suggesting that its functions in skin may be different from those in neurones. Thus, although the LAT locus was previously thought to be dispensable for lytic infection, we show that it is a determinant of HSV-1 virulence during lytic infection of human skin.

scholarly journals Neurodegeneration in human brain organoids infected with herpes simplex virus type 1

2021 ◽  
Author(s):  
Agnieszka Rybak-Wolf ◽  
Emanuel Wyler ◽  
Ivano Legnini ◽  
Anna Loewa ◽  
Petar Glažar ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Human Brain ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Cell Type ◽  
Cell Type Specific ◽  
Simplex Virus ◽  
Hsv 1

AbstractHerpes simplex virus type 1 (HSV-1) infection of the nervous system may lead to brain damage, including neurodegeneration. However, lack of suitable experimental models hinders understanding molecular mechanisms and cell-type-specific responses triggered by HSV-1. Here, we infected human brain organoids with HSV-1. Known features of HSV-1 infection such as alteration of neuronal electrophysiology and induction of antisense transcription were confirmed. Full-length mRNA-sequencing revealed aberrant 3’ end formation and poly(A)-tail lengthening. Single-cell RNA-seq and spatial transcriptomics uncovered changes in the cellular composition of the infected organoids caused by viral replication and dysregulation of molecular pathways in cell-type specific manner. Furthermore, hallmarks of early neurodegeneration were observed, namely extracellular matrix disruption, STMN2 and TARDBP/TDP43 downregulation, and upregulation of the AD-related non-coding RNA BC200/BCYRN1. These hallmarks were weaker/absent when infecting with a mutant HSV-1 control. Together, our data indicate that brain organoids serve as a powerful model to study mechanisms of HSV-1-driven neurodegeneration.

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