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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 -
Medicine Nov 2022Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using... (Review)
Review
Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.
Topics: Humans; Child; Infant, Newborn; Infant; Child, Preschool; Adolescent; Cross-Sectional Studies; Meningitis, Viral; Herpesvirus 2, Human; Herpesvirus 1, Human; Herpesvirus 3, Human; Enterovirus; Viruses; Parechovirus; Nucleic Acids
PubMed: 36401437
DOI: 10.1097/MD.0000000000031588 -
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 Sep 2015Alphaherpesviruses like herpes simplex virus are large DNA viruses characterized by their ability to establish lifelong latent infection in neurons. As for all... (Review)
Review
Alphaherpesviruses like herpes simplex virus are large DNA viruses characterized by their ability to establish lifelong latent infection in neurons. As for all herpesviruses, alphaherpesvirus virions contain a protein-rich layer called "tegument" that links the DNA-containing capsid to the glycoprotein-studded membrane envelope. Tegument proteins mediate a diverse range of functions during the virus lifecycle, including modulation of the host-cell environment immediately after entry, transport of virus capsids to the nucleus during infection, and wrapping of cytoplasmic capsids with membranes (secondary envelopment) during virion assembly. Eleven tegument proteins that are conserved across alphaherpesviruses have been implicated in the formation of the tegument layer or in secondary envelopment. Tegument is assembled via a dense network of interactions between tegument proteins, with the redundancy of these interactions making it challenging to determine the precise function of any specific tegument protein. However, recent studies have made great headway in defining the interactions between tegument proteins, conserved across alphaherpesviruses, which facilitate tegument assembly and secondary envelopment. We summarize these recent advances and review what remains to be learned about the molecular interactions required to assemble mature alphaherpesvirus virions following the release of capsids from infected cell nuclei.
Topics: Alphaherpesvirinae; Models, Biological; Protein Binding; Viral Structural Proteins; Virus Assembly
PubMed: 26393641
DOI: 10.3390/v7092861 -
Viruses Apr 2022Randall Cohrs established the Colorado Alphaherpesvirus Latency Society (CALS) in 2011 [...].
Randall Cohrs established the Colorado Alphaherpesvirus Latency Society (CALS) in 2011 [...].
Topics: Alphaherpesvirinae; Colorado; Oncogenic Viruses
PubMed: 35632657
DOI: 10.3390/v14050915 -
Viruses Jun 2022Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, is one of the most important infectious pathogens threatening the global pig industry. Like other... (Review)
Review
Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, is one of the most important infectious pathogens threatening the global pig industry. Like other members of alphaherpesviruses, PRV establishes a lifelong latent infection and occasionally reactivates from latency after stress stimulus in infected pigs. Latent infected pigs can then serve as the source of recurrent infection, which is one of the difficulties for PRV eradication. Virus latency refers to the retention of viral complete genomes without production of infectious progeny virus; however, following stress stimulus, the virus can be reactivated into lytic infection, which is known as the latency-reactivation cycle. Recently, several research have indicated that alphaherpesvirus latency and reactivation is regulated by a complex interplay between virus, neurons, and the immune system. However, with those limited reports, the relevant advances in PRV latency are lagging behind. Therefore, in this review we focus on the regulatory mechanisms in PRV latency via summarizing the progress of PRV itself and that of other alphaherpesviruses, which will improve our understanding in the underlying mechanism of PRV latency and help design novel therapeutic strategies to control PRV latency.
Topics: Animals; Genome, Viral; Herpesvirus 1, Suid; Neurons; Pseudorabies; Swine; Virus Latency
PubMed: 35891367
DOI: 10.3390/v14071386 -
Current Issues in Molecular Biology 2021We are at an interesting time in the understanding of alpha herpesvirus latency and reactivation and their implications to human disease. Conceptual advances have come... (Review)
Review
We are at an interesting time in the understanding of alpha herpesvirus latency and reactivation and their implications to human disease. Conceptual advances have come from both animal and neuronal culture models. This review focuses on the concept that the tegument protein and viral transactivator VP16 plays a major role in the transition from latency to the lytic cycle. During acute infection, regulation of VP16 transactivation balances spread in the nervous system, establishment of latent infections and virulence. Reactivation is dependent on this transactivator to drive entry into the lytic cycle. In vivo de novo expression of VP16 protein is mediated by sequences conferring pre-immediate early transcription embedded in the normally leaky late promoter. In vitro, alternate mechanisms regulating VP16 expression in the context of latency have come from the SCG neuron culture model and include the concepts that (i) generalized transcriptional derepression of the viral genome and sequestration of VP16 in the cytoplasm for ~48 hours (Phase I) precedes and is required for VP16-dependent reactivation (Phase II); and (ii) a histone methyl/phospho switch during Phase I is required for Phase II reactivation. The challenge to the field is reconciling these data into a unified model of virus reactivation. The task of compiling this review was uncomfortably humbling, as if cataloging the stars in the universe. While not completely dark, our night sky is missing a multitude of studies which are among the many points of light contributing to our field. This article is a focused review in which we discuss from the vantage point of our expertise, just a handful of concepts that have or are emerging. A lookback at some of the pioneering work that grounds our field is also included.
Topics: Alphaherpesvirinae; Animals; Genome, Viral; Herpes Simplex; Herpes Simplex Virus Protein Vmw65; Humans; Latent Infection; Neurons; Simplexvirus; Transcription, Genetic; Virus Latency
PubMed: 32883886
DOI: 10.21775/cimb.041.267 -
Viruses Oct 2023Herpesviruses are enveloped and have an amorphous protein layer surrounding the capsid, which is termed the tegument. Tegument proteins perform critical functions... (Review)
Review
Herpesviruses are enveloped and have an amorphous protein layer surrounding the capsid, which is termed the tegument. Tegument proteins perform critical functions throughout the viral life cycle. This review provides a comprehensive and comparative analysis of the roles of specific tegument proteins in capsid transport and virion morphogenesis of selected, well-studied prototypes of each of the three subfamilies of i.e., human herpesvirus-1/herpes simplex virus-1 (), human herpesvirus-5/cytomegalovirus () and human herpesvirus -8/Kaposi's sarcomavirus (). Most of the current knowledge is based on alpha herpesviruses, in particular HSV-1. While some tegument proteins are released into the cytoplasm after virus entry, several tegument proteins remain associated with the capsid and are responsible for transport to and docking at the nucleus. After replication and capsid formation, the capsid is enveloped at the nuclear membrane, which is referred to as primary envelopment, followed by de-envelopment and release into the cytoplasm. This requires involvement of at least three tegument proteins. Subsequently, multiple interactions between tegument proteins and capsid proteins, other tegument proteins and glycoproteins are required for assembly of the virus particles and envelopment at the Golgi, with certain tegument proteins acting as the central hub for these interactions. Some redundancy in these interactions ensures appropriate morphogenesis.
Topics: Humans; Capsid Proteins; Capsid; Virus Assembly; Herpesviridae; Herpesvirus 1, Human; Herpesvirus 8, Human; Morphogenesis; Virion; Viral Structural Proteins
PubMed: 37896835
DOI: 10.3390/v15102058 -
Viruses Jul 2011Following infection of exposed peripheral tissues, neurotropic alphaherpesviruses invade nerve endings and deposit their DNA genomes into the nuclei of neurons resident... (Review)
Review
Following infection of exposed peripheral tissues, neurotropic alphaherpesviruses invade nerve endings and deposit their DNA genomes into the nuclei of neurons resident in ganglia of the peripheral nervous system. The end result of these events is the establishment of a life-long latent infection. Neuroinvasion typically requires efficient viral transmission through a polarized epithelium followed by long-distance transport through the viscous axoplasm. These events are mediated by the recruitment of the cellular microtubule motor proteins to the intracellular viral particle and by alterations to the cytoskeletal architecture. The focus of this review is the interplay between neurotropic herpesviruses and the cytoskeleton.
Topics: Alphaherpesvirinae; Animals; Cytoskeleton; Herpesviridae Infections; Humans; Neurons; Peripheral Nervous System Diseases
PubMed: 21994765
DOI: 10.3390/v3070941 -
Viruses Feb 2013Alphaherpesviruses are pathogens that invade the nervous systems of their mammalian hosts. Directional spread of infection in the nervous system is a key component of... (Review)
Review
Alphaherpesviruses are pathogens that invade the nervous systems of their mammalian hosts. Directional spread of infection in the nervous system is a key component of the viral lifecycle and is critical for the onset of alphaherpesvirus-related diseases. Many alphaherpesvirus infections originate at peripheral sites, such as epithelial tissues, and then enter neurons of the peripheral nervous system (PNS), where lifelong latency is established. Following reactivation from latency and assembly of new viral particles, the infection typically spreads back out towards the periphery. These spread events result in the characteristic lesions (cold sores) commonly associated with herpes simplex virus (HSV) and herpes zoster (shingles) associated with varicella zoster virus (VZV). Occasionally, the infection spreads transsynaptically from the PNS into higher order neurons of the central nervous system (CNS). Spread of infection into the CNS, while rarer in natural hosts, often results in severe consequences, including death. In this review, we discuss the viral and cellular mechanisms that govern directional spread of infection in the nervous system. We focus on the molecular events that mediate long distance directional transport of viral particles in neurons during entry and egress.
Topics: Alphaherpesvirinae; Animals; Biological Transport; Cytoskeleton; Humans; Nervous System; Neurons
PubMed: 23435239
DOI: 10.3390/v5020678