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Viruses Mar 2022The non-specific innate immunity can initiate host antiviral innate immune responses within minutes to hours after the invasion of pathogenic microorganisms. Therefore,... (Review)
Review
The non-specific innate immunity can initiate host antiviral innate immune responses within minutes to hours after the invasion of pathogenic microorganisms. Therefore, the natural immune response is the first line of defense for the host to resist the invaders, including viruses, bacteria, fungi. Host pattern recognition receptors (PRRs) in the infected cells or bystander cells recognize pathogen-associated molecular patterns (PAMPs) of invading pathogens and initiate a series of signal cascades, resulting in the expression of type I interferons (IFN-I) and inflammatory cytokines to antagonize the infection of microorganisms. In contrast, the invading pathogens take a variety of mechanisms to inhibit the induction of IFN-I production from avoiding being cleared. Pseudorabies virus (PRV) belongs to the family Herpesviridae, subfamily Alphaherpesvirinae, genus Varicellovirus. PRV is the causative agent of Aujeszky's disease (AD, pseudorabies). Although the natural host of PRV is swine, it can infect a wide variety of mammals, such as cattle, sheep, cats, and dogs. The disease is usually fatal to these hosts. PRV mainly infects the peripheral nervous system (PNS) in swine. For other species, PRV mainly invades the PNS first and then progresses to the central nervous system (CNS), which leads to acute death of the host with serious clinical and neurological symptoms. In recent years, new PRV variant strains have appeared in some areas, and sporadic cases of PRV infection in humans have also been reported, suggesting that PRV is still an important emerging and re-emerging infectious disease. This review summarizes the strategies of PRV evading host innate immunity and new targets for inhibition of PRV replication, which will provide more information for the development of effective inactivated vaccines and drugs for PRV.
Topics: Animals; Antiviral Agents; Cattle; Dogs; Herpesvirus 1, Suid; Immunity, Innate; Mammals; Pseudorabies; Sheep; Swine; Virus Replication
PubMed: 35336954
DOI: 10.3390/v14030547 -
Viruses Jan 2023Pseudorabies virus (PRV) is the pathogen of pseudorabies (PR), which belongs to the alpha herpesvirus subfamily with a double stranded DNA genome encoding approximately... (Review)
Review
Pseudorabies virus (PRV) is the pathogen of pseudorabies (PR), which belongs to the alpha herpesvirus subfamily with a double stranded DNA genome encoding approximately 70 proteins. PRV has many non-essential regions for replication, has a strong capacity to accommodate foreign genes, and more areas for genetic modification. PRV is an ideal vaccine vector, and multivalent live virus-vectored vaccines can be developed using the gene-deleted PRV. The immune system continues to be stimulated by the gene-deleted PRVs and maintain a long immunity lasting more than 4 months. Here, we provide a brief overview of the biology of PRV, recombinant PRV construction methodology, the technology platform for efficiently constructing recombinant PRV, and the applications of recombinant PRV in vaccine development. This review summarizes the latest information on PRV usage in vaccine development against swine infectious diseases, and it offers novel perspectives for advancing preventive medicine through vaccinology.
Topics: Animals; Swine; Pseudorabies; Herpesvirus 1, Suid; Communicable Diseases; Alphaherpesvirinae; Vaccine Development; Orthopoxvirus; Vaccines, Combined
PubMed: 36851584
DOI: 10.3390/v15020370 -
Current Issues in Molecular Biology 2021Herpesviruses virions are large and complex structures that deliver their genetic content to nuclei upon entering cells. This property is not unusual as many other... (Review)
Review
Herpesviruses virions are large and complex structures that deliver their genetic content to nuclei upon entering cells. This property is not unusual as many other viruses including the adenoviruses, orthomyxoviruses, papillomaviruses, polyomaviruses, and retroviruses, do likewise. However, the means by which viruses in the subfamily accomplish this fundamental stage of the infectious cycle is tied to their defining ability to efficiently invade the nervous system. Fusion of the viral envelope with a cell membrane results in the deposition of the capsid, along with an assortment of tegument proteins, into the cytosol. Establishment of infection requires that the capsid traverse the cytosol, dock at a nuclear pore, and inject its genome into the nucleoplasm. Accumulating evidence indicates that the capsid is not the effector of this delivery process, but is instead shepherded by tegument proteins that remain capsid bound. At the same time, tegument proteins that are released from the capsid upon entry act to increase the susceptibility of the cell to the ensuing infection. Mucosal epithelial cells and neurons are both susceptible to alphaherpesvirus infection and, together, provide the niche to which these viruses have adapted. Although much has been revealed about the functions of expressed tegument proteins during the late stages of assembly and egress, this review will specifically address the roles of tegument proteins brought into the cell with the incoming virion, and our current understanding of alphaherpesvirus genome delivery to nuclei.
Topics: Alphaherpesvirinae; Animals; Capsid Proteins; Cell Nucleus; Cytoplasm; Genome, Viral; Herpesviridae Infections; Humans; Virion; Virus Assembly; Virus Internalization
PubMed: 32807747
DOI: 10.21775/cimb.041.171 -
Klinicka Onkologie : Casopis Ceske a... 2018Seroepidemiological studies suggest that human herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) are linked with several types of cancer; however, they do not appear to... (Review)
Review
Seroepidemiological studies suggest that human herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) are linked with several types of cancer; however, they do not appear to play a direct role and are considered to be cofactors. The abilities of HSV-1 and -2 to transform cells in vitro can be demonstrated by suppressing their lytic ability via irradiation with a specific dose of ultraviolet light, photoinactivation in the presence of photosensitizers (e.g., neutral red or methylene blue), and culture under specific conditions. Several mechanisms have been proposed to explain the actions of these viruses. According to the hit-and-run mechanism, viral DNA initiates transformation by interacting with cellular DNA and thereby inducing mutations and epigenetic changes, but is not involved in other stages of neoplastic progression. By contrast, according to the hijacking mechanism, viral products in infected cells can activate signaling pathways and thereby cause uncontrolled proliferation. Such products include RR1PK, an oncoprotein that activates the Ras pathway and is encoded by the HSV-2 gene ICP10. Virus-encoded microRNAs may act as cofactors in tumorigenesis of serous ovarian carcinoma and some prostate tumors. Herpes virus-associated growth factors that facilitate or suppress transformation may play important roles in tumor formation. Finally, there is much evidence that HSV-2 increases the risk of cervical cancer after infection of human papilloma viruses. Key words: HSV-1 - HSV-2 - cancer - mechanisms of transformation This work was supported by APVV 0621-12. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 29. 11. 2016 Accepted: 20. 3. 2018.
Topics: Cell Transformation, Viral; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Neoplasms
PubMed: 30441970
DOI: 10.14735/amko2018178 -
Proteomics Jun 2015Viruses are intracellular parasites that can only replicate and spread in cells of susceptible hosts. Alpha herpesviruses (α-HVs) contain double-stranded DNA genomes of... (Review)
Review
Viruses are intracellular parasites that can only replicate and spread in cells of susceptible hosts. Alpha herpesviruses (α-HVs) contain double-stranded DNA genomes of at least 120 kb, encoding for 70 or more genes. The viral genome is contained in an icosahedral capsid that is surrounded by a proteinaceous tegument layer and a lipid envelope. Infection starts in epithelial cells and spreads to the peripheral nervous system. In the natural host, α-HVs establish a chronic latent infection that can be reactivated and rarely spread to the CNS. In the nonnatural host, viral infection will in most cases spread to the CNS with often fatal outcome. The host response plays a crucial role in the outcome of viral infection. α-HVs do not encode all the genes required for viral replication and spread. They need a variety of host gene products including RNA polymerase, ribosomes, dynein, and kinesin. As a result, the infected cell is dramatically different from the uninfected cell revealing a complex and dynamic interplay of viral and host components required to complete the virus life cycle. In this review, we describe the pivotal contribution of MS-based proteomics studies over the past 15 years to understand the complicated life cycle and pathogenesis of four α-HV species from the alphaherpesvirinae subfamily: Herpes simplex virus-1, varicella zoster virus, pseudorabies virus and bovine herpes virus-1. We describe the viral proteome dynamics during host infection and the host proteomic response to counteract such pathogens.
Topics: Alphaherpesvirinae; Animals; Cattle; Herpesviridae Infections; Host-Pathogen Interactions; Mass Spectrometry; Proteome; Proteomics; Viral Proteins; Virus Replication
PubMed: 25764121
DOI: 10.1002/pmic.201400604 -
The American Journal of Dermatopathology Aug 2014Herpes simplex virus and varicella zoster virus are double-stranded DNA viruses that commonly infect humans, resulting in cutaneous manifestations. Diagnosis is... (Review)
Review
Herpes simplex virus and varicella zoster virus are double-stranded DNA viruses that commonly infect humans, resulting in cutaneous manifestations. Diagnosis is generally made based on clinical findings; however, when the presentation is atypical, biopsy can aid in making a correct diagnosis. The classic histopathological findings of herpetic infection are well established (acantholysis, ballooning degeneration, intranuclear inclusions, multinucleation, necrosis, and formation of vesicles or ulcers). Herpes infection can also cause histopathological changes in many dermal structures. Furthermore, herpes can masquerade as a variety of hematologic malignancies or benign cutaneous conditions. The histopathological spectrum of herpes infections is reviewed and discussed.
Topics: Biopsy; Diagnosis, Differential; Herpes Simplex; Herpesvirus 3, Human; Humans; Predictive Value of Tests; Simplexvirus; Skin; Skin Diseases, Viral
PubMed: 25051039
DOI: 10.1097/DAD.0000000000000148 -
Methods in Molecular Biology (Clifton,... 2020Virus vectors have been employed as gene transfer vehicles for various preclinical and clinical gene therapy applications and with the approval of Glybera (Alipogene...
Virus vectors have been employed as gene transfer vehicles for various preclinical and clinical gene therapy applications and with the approval of Glybera (Alipogene tiparvovec) as the first gene therapy product as a standard medical treatment (Yla-Herttuala, Mol Ther 20:1831-1832, 2013), gene therapy has reached the status of being a part of standard patient care. Replication-competent herpes simplex virus (HSV) vectors that replicate specifically in actively dividing tumor cells have been used in Phase I-III human trials in patients with glioblastoma multiforme (GBM), a fatal form of brain cancer, and in malignant melanoma. In fact, Imlygic (T-VEC, Talimogene laherparepvec, formerly known as OncoVex GM-CSF), displayed efficacy in a recent Phase-III trial when compared to standard GM-CSF treatment alone (Andtbacka et al., J Clin Oncol 31:sLBA9008, 2013), and has since become the first FDA-approved viral gene therapy product used in standard patient care (October 2015) (Pol et al., Oncoimmunology 5:e1115641, 2016). Moreover, increased efficacy was observed when Imlygic was combined with checkpoint inhibitory antibodies as a frontline therapy for malignant melanoma (Ribas et al., Cell 170:1109-1119.e1110, 2017; Dummer et al., Cancer Immunol Immunother 66:683-695, 2017). In addition to the replication-competent oncolytic HSV vectors like T-VEC, replication-defective HSV vectors have been employed in Phase I-II human trials and have been explored as delivery vehicles for disorders such as pain, neuropathy and other neurodegenerative conditions. Research during the last decade on the development of HSV vectors has resulted in the engineering of recombinant vectors that are completely replication defective, nontoxic, and capable of long-term transgene expression in neurons. This chapter describes methods for the construction of recombinant genomic HSV vectors based on the HSV-1 replication-defective vector backbones, steps in their purification, and their small-scale production for use in cell culture experiments as well as preclinical animal studies.
Topics: Animals; Chlorocebus aethiops; Genetic Therapy; Genetic Vectors; Herpesvirus 1, Human; Humans; Transgenes; Vero Cells
PubMed: 31617173
DOI: 10.1007/978-1-4939-9814-2_4 -
Folia Microbiologica Jun 2020Based on seroepidemiological studies, human herpes simplex virus types 1 and 2 (HSV-1, HSV-2) are put in relation with a number of cancer diseases; however, they do not... (Review)
Review
Based on seroepidemiological studies, human herpes simplex virus types 1 and 2 (HSV-1, HSV-2) are put in relation with a number of cancer diseases; however, they do not appear to play a direct role, being only considered cofactors. Their ability to transform the cells in vitro could be demonstrated experimentally by removing their high lytic ability by a certain dose of UV radiation or by photoinactivation in the presence of photosensitizers, such as neutral red or methylene blue, or culturing under conditions suppressing their lytic activity. However, recent studies indicate that UV irradiated or photoinactivated HSV-1 and HSV-2, able to transform non-transformed cells, behave differently in transformed cells suppressing their transformed phenotype. Furthermore, both transforming and transformed phenotype suppressing activities are pertaining only to non-syncytial virus strains. There are some proposed mechanisms explaining their transforming activity. According to the "hit and run" mechanism, viral DNA induces only initiation of transformation by interacting with cellular DNA bringing about mutations and epigenetic changes and is no longer involved in other processes of neoplastic progression. According to the "hijacking" mechanism, virus products in infected cells may activate signalling pathways and thus induce uncontrolled proliferation. Such a product is e.g. a product of HSV-2 gene designated ICP10 that encodes an oncoprotein RR1PK that activates the Ras pathway. In two cases of cancer, in the case of serous ovarian carcinoma and in some prostate tumours, virus-encoded microRNAs (miRNAs) were detected as a possible cofactor in tumorigenesis. And, recently described herpes virus-associated growth factors with transforming and transformation repressing activity might be considered important factors playing a role in tumour formation. And finally, there is a number of evidence that HSV-2 may increase the risk of cervical cancer after infection with human papillomaviruses. A similar situation is with human cytomegalovirus; however, here, a novel mechanism named oncomodulation has been proposed. Oncomodulation means that HCMV infects tumour cells and modulates their malignant properties without having a direct effect on cell transformation.
Topics: Cell Transformation, Viral; DNA, Viral; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Neoplasms
PubMed: 32072398
DOI: 10.1007/s12223-020-00780-x -
International Journal of Molecular... Nov 2020Oncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to... (Review)
Review
Oncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to self-exhaust upon tumor clearance. Oncolytic virotherapy strategies based on the herpes simplex virus are reaching their thirties, and a wide variety of approaches has been envisioned and tested in many different models, and on a range of tumor targets. This huge effort has culminated in the primacy of an oncolytic HSV (oHSV) being the first oncolytic virus to be approved by the FDA and EMA for clinical use, for the treatment of advanced melanoma. The path has just been opened; many more cancer types with poor prognosis await effective and innovative therapies, and oHSVs could provide a promising solution, especially as combination therapies and immunovirotherapies. In this review, we analyze the most recent advances in this field, and try to envision the future ahead of oHSVs.
Topics: Combined Modality Therapy; Herpesvirus 1, Human; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Simplexvirus
PubMed: 33167582
DOI: 10.3390/ijms21218310 -
Viruses May 2024Marek's disease (MD), caused by (GaAHV2) or Marek's disease herpesvirus (MDV), is a devastating disease in chickens characterized by the development of lymphomas...
Marek's disease (MD), caused by (GaAHV2) or Marek's disease herpesvirus (MDV), is a devastating disease in chickens characterized by the development of lymphomas throughout the body. Vaccine strains used against MD include 3 (GaAHV3), a non-oncogenic chicken alphaherpesvirus homologous to MDV, and homologous meleagrid alphaherpesvirus 1 (MeAHV1) or turkey herpesvirus (HVT). Previous work has shown most of the MDV gC produced during in vitro passage is secreted into the media of infected cells although the predicted protein contains a transmembrane domain. We formerly identified two alternatively spliced gC mRNAs that are secreted during MDV replication in vitro, termed gC104 and gC145 based on the size of the intron removed for each (gC) transcript. Since gC is conserved within the subfamily, we hypothesized GaAHV3 (strain 301B/1) and HVT also secrete gC due to mRNA splicing. To address this, we collected media from 301B/1- and HVT-infected cell cultures and used Western blot analyses and determined that both 301B/1 and HVT produced secreted gC. Next, we extracted RNAs from 301B/1- and HVT-infected cell cultures and chicken feather follicle epithelial (FFE) skin cells. RT-PCR analyses confirmed one splicing variant for 301B/1 gC (gC104) and two variants for HVT gC (gC104 and gC145). Interestingly, the splicing between all three viruses was remarkably conserved. Further analysis of predicted and validated mRNA splicing donor, branch point (BP), and acceptor sites suggested single nucleotide polymorphisms (SNPs) within the 301B/1 transcript sequence resulted in no gC145 being produced. However, modification of the 301B/1 gC145 donor, BP, and acceptor sites to the MDV sequences did not result in gC145 mRNA splice variant, suggesting mRNA splicing is more complex than originally hypothesized. In all, our results show that mRNA splicing of avian herpesviruses is conserved and this information may be important in developing the next generation of MD vaccines or therapies to block transmission.
Topics: Animals; Chickens; RNA Splicing; Viral Envelope Proteins; RNA, Messenger; Marek Disease; Mardivirus; Viral Proteins; Herpesvirus 2, Gallid; Alternative Splicing; Antigens, Viral
PubMed: 38793663
DOI: 10.3390/v16050782