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Viruses Jun 2022Pseudorabies virus (PRV) can cause neurological, respiratory, and reproductive diseases in pigs and establish lifelong latent infection in the peripheral nervous system... (Review)
Review
Pseudorabies virus (PRV) can cause neurological, respiratory, and reproductive diseases in pigs and establish lifelong latent infection in the peripheral nervous system (PNS). Latent infection is a typical feature of PRV, which brings great difficulties to the prevention, control, and eradication of pseudorabies. The integral mechanism of latent infection is still unclear. Latency-associated transcripts (LAT) gene is the only transcriptional region during latent infection of PRV which plays the key role in regulating viral latent infection and inhibiting apoptosis. Here, we review the characteristics of PRV latent infection and the transcriptional characteristics of the LAT gene. We also analyzed the function of non-coding RNA (ncRNA) produced by the LAT gene and its importance in latent infection. Furthermore, we provided possible strategies to solve the problem of latent infection of virulent PRV strains in the host. In short, the detailed mechanism of PRV latent infection needs to be further studied and elucidated.
Topics: Animals; Herpesvirus 1, Suid; Latent Infection; Pseudorabies; Swine; Swine Diseases
PubMed: 35891360
DOI: 10.3390/v14071379 -
Journal of Virology May 2022Herpesviruses assemble new viral particles in the nucleus. These nucleocapsids bud through the inner nuclear membrane to produce enveloped viral particles in the...
Herpesviruses assemble new viral particles in the nucleus. These nucleocapsids bud through the inner nuclear membrane to produce enveloped viral particles in the perinuclear space before fusing with the outer nuclear membrane to reach the cytoplasm. This unusual route is necessary since viral capsids are too large to pass through nuclear pores. However, the transient perinuclear nucleocapsids (250 nm in diameter) are also larger than the width of the perinuclear space (30 to 50 nm). Interestingly, linker of the nucleoskeleton and cytoskeleton (LINC) components SUN and KASH connect the inner and outer nuclear membranes and regulate their spacing. Previous work by others on the related pseudorabies virus and human cytomegalovirus showed that they functionally interact with SUN proteins. To clarify the role of SUN proteins, we explored their impact on herpes simplex virus 1 (HSV-1), another herpesvirus. Using dominant negative SUN mutants and RNA interference, we show that HSV-1 propagation is dependent on the LINC complex. In contrast to pseudorabies virus, SUN2 disruption by either approach led to increased HSV-1 extracellular viral yields. This SUN2 dependency may be linked to its greater impact on perinuclear spacing in infected cells compared to SUN1. Finally, the virus itself seems to modulate perinuclear spacing. The large size of herpesviruses prevents them from travelling across the nuclear pores, and they instead egress across the two nuclear membranes, generating short-lived enveloped perinuclear virions. This poses a challenge as the perinuclear space is smaller than the virions. This implies the separation (unzipping) of the two nuclear membranes to accommodate the viral particles. The LINC complex bridges the two nuclear membranes and is an important regulator of perinuclear spacing. Work by others hint at its functional implication during pseudorabies virus and cytomegalovirus propagation. The present study probes the importance for HSV-1 of the SUN proteins, the LINC components found in the inner nuclear membrane. Using dominant negative constructs and RNA interference (RNAi), the data reveal that SUN2 exhibits antiviral propriety toward HSV-1, as disrupting the protein leads to increased viral yields. This is in contrast with that reported for pseudorabies and suggests that differences among herpesviruses may, once again, prevail.
Topics: Animals; Cell Nucleus; Herpesvirus 1, Human; Herpesvirus 1, Suid; Humans; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Nuclear Envelope; Nucleocapsid; Virion
PubMed: 35435724
DOI: 10.1128/jvi.00453-22 -
Journal of the American Academy of... Mar 2023
Topics: Humans; Pemphigus; Herpes Simplex; Herpesvirus 1, Human
PubMed: 36720366
DOI: 10.1016/j.jaad.2023.01.018 -
Clinical Journal of Oncology Nursing May 2023Herpes simplex virus (HSV) encephalitis (HSVE), which is caused by HSV-1 or HSV-2, is a rare neurologic disorder associated with focal or global cerebral dysfunction....
Herpes simplex virus (HSV) encephalitis (HSVE), which is caused by HSV-1 or HSV-2, is a rare neurologic disorder associated with focal or global cerebral dysfunction. HSVE is a syndrome of altered mental status, fever, and se.
Topics: Humans; Herpes Simplex; Simplexvirus; Encephalitis
PubMed: 37267490
DOI: 10.1188/23.CJON.237-241 -
Frontiers in Immunology 2019Alphaherpesviruses are a large family of highly successful human and animal DNA viruses that can establish lifelong latent infection in neurons. All alphaherpesviruses... (Review)
Review
Alphaherpesviruses are a large family of highly successful human and animal DNA viruses that can establish lifelong latent infection in neurons. All alphaherpesviruses have a protein-rich layer called the tegument that, connects the DNA-containing capsid to the envelope. Tegument proteins have a variety of functions, playing roles in viral entry, secondary envelopment, viral capsid nuclear transportation during infection, and immune evasion. Recently, many studies have made substantial breakthroughs in characterizing the innate immune evasion of tegument proteins. A wide range of antiviral tegument protein factors that control incoming infectious pathogens are induced by the type I interferon (IFN) signaling pathway and other innate immune responses. In this review, we discuss the immune evasion of tegument proteins with a focus on herpes simplex virus type I.
Topics: Alphaherpesvirinae; Animals; Herpesvirus 1, Human; Humans; Immune Evasion; Immunity, Innate; Signal Transduction; Viral Structural Proteins; Virus Internalization; Virus Replication
PubMed: 31572398
DOI: 10.3389/fimmu.2019.02196 -
Nature Communications Dec 2023Herpesviruses remain a burden for animal and human health, including the medically important varicella-zoster virus (VZV). Membrane fusion mediated by conserved core...
Herpesviruses remain a burden for animal and human health, including the medically important varicella-zoster virus (VZV). Membrane fusion mediated by conserved core glycoproteins, the fusogen gB and the heterodimer gH-gL, enables herpesvirus cell entry. The ectodomain of gB orthologs has five domains and is proposed to transition from a prefusion to postfusion conformation but the functional relevance of the domains for this transition remains poorly defined. Here we describe structure-function studies of the VZV gB DIII central helix targeting residues EHV. Critically, a H527P mutation captures gB in a prefusion conformation as determined by cryo-EM, a loss of membrane fusion in a virus free assay, and failure of recombinant VZV to spread in cell monolayers. Importantly, two predominant cryo-EM structures of gB[H527P] are identified by 3D classification and focused refinement, suggesting they represented gB conformations in transition. These studies reveal gB DIII as a critical element for herpesvirus gB fusion function.
Topics: Animals; Humans; Viral Envelope Proteins; Mutagenesis; Mutation; Herpesvirus 3, Human; Herpesvirus 1, Human; Virus Internalization
PubMed: 38042814
DOI: 10.1038/s41467-023-43011-w -
Experimental Neurology May 2022It has become widely appreciated that the spinal cord has significant neuroplastic potential, is not hard-wired, and that with traumatic injury and anatomical... (Review)
Review
It has become widely appreciated that the spinal cord has significant neuroplastic potential, is not hard-wired, and that with traumatic injury and anatomical plasticity, the networks that we once understood now comprise a new anatomy. Harnessing advances in neuroanatomical tracing to map the neuronal networks of the intact and injured spinal cord has been crucial to elucidating this new spinal cord anatomy. Many new techniques have been developed to identify these networks using a variety of retrograde and anterograde tracers. One method of tracing that has become more widely used to map anatomical changes is transneuronal tracing. Viral tracers are being increasingly used to map spinal networks, leading to an advanced understanding of spinal circuitry and host-donor-host interactions between the injured spinal cord and neural transplants. This review will highlight advances in neuronal tracing, specifically using pseudorabies virus (PRV), and its use in the intact, injured, and transplanted spinal cord.
Topics: Animals; Herpesvirus 1, Suid; Neuronal Plasticity; Neurons; Spinal Cord; Spinal Cord Injuries
PubMed: 35085573
DOI: 10.1016/j.expneurol.2022.113990 -
Nature Communications Dec 2022Monosynaptic viral tracers are essential tools for dissecting neuronal connectomes and for targeted delivery of molecular sensors and effectors. Viral toxicity and...
Monosynaptic viral tracers are essential tools for dissecting neuronal connectomes and for targeted delivery of molecular sensors and effectors. Viral toxicity and complex multi-injection protocols are major limiting application barriers. To overcome these barriers, we developed an anterograde monosynaptic H129 tracer system based on HSV-1 strain H129. The H129 tracer system consists of two components: an H129-dTK-T2-pac helper which assists H129 tracer's propagation and transneuronal monosynaptic transmission. The shared viral features of tracer/helper allow for simultaneous single-injection and subsequent high expression efficiency from multiple-copy of expression cassettes in H129 tracer. These improvements of H129 tracer system shorten experiment duration from 28-day to 5-day for fast-bright monosynaptic tracing. The lack of toxic viral genes in the H129 tracer minimizes toxicity in postsynaptic neurons, thus offering the potential for functional anterograde mapping and long-term tracer delivery of genetic payloads. The H129 tracer system is a powerful tracing tool for revealing neuronal connectomes.
Topics: Herpesvirus 1, Human; Neurons; Connectome; Nerve Net
PubMed: 36496505
DOI: 10.1038/s41467-022-35355-6 -
Trends in Microbiology Jan 2023Herpesviruses hijack the MHC class I (MHC I) and class II (MHC II) antigen-presentation pathways to manipulate immune recognition by T cells. First, we illustrate herpes... (Review)
Review
Herpesviruses hijack the MHC class I (MHC I) and class II (MHC II) antigen-presentation pathways to manipulate immune recognition by T cells. First, we illustrate herpes simplex virus-1 (HSV-1) and varicella-zoster virus (VZV) MHC immune evasion strategies. Next, we describe MHC-T cell interactions in HSV-1- and VZV- infected neural ganglia. Although studies on the topic are scarce, and use different models, most reports indicate that neuronal HSV-1 infection is mainly controlled by CD8+ T cells through noncytolytic mechanisms, whereas VZV seems to be largely controlled through CD4+ T cell-specific immune responses. Autologous human stem-cell-derived in vitro models could substantially aid in elucidating these neuroimmune interactions and are fit for studies on both herpesviruses.
Topics: Humans; Herpesvirus 3, Human; Herpesvirus 1, Human; Herpes Zoster; Herpes Simplex; Ganglia
PubMed: 35987880
DOI: 10.1016/j.tim.2022.07.008 -
International Journal of Molecular... Jul 2023The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of...
The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes simplex viruses 1 and 2 (HSV1 and HSV2), well-known human pathogens that can cause lifelong infections, can induce changes in MSCs. In non-healing ulcers, HSV infection is known to affect deeper tissue layers. In addition, HSV infection can recur after initially successful cell therapies. Our aim was to study the response of adipose-derived MSCs (ADMSCs) to HSV infection in vitro. After confirming the phenotype and differentiation capacity of the isolated cells, we infected the cells in vitro with HSV1-KOS, HSV1-532 and HSV2 virus strains. Twenty-four hours after infection, we examined the gene expression of the cells via RNA-seq and RT-PCR; detected secreted cytokines via protein array; and determined autophagy via Western blot, transmission electron microscopy (TEM) and fluorescence microscopy. Infection with different HSV strains resulted in different gene-expression patterns. In addition to the activation of pathways characteristic of viral infections, distinct non-immunological pathways (autophagy, tissue regeneration and differentiation) were also activated according to analyses with QIAGEN Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genome and Genome Ontology Enrichment. Viral infections increased autophagy, as confirmed via TEM image analysis, and also increased levels of the microtubule-associated protein light chain 3 (LC3B) II protein. We identified significantly altered accumulation for 16 cytokines involved in tissue regeneration and inflammation. Our studies demonstrated that HSV infection can alter the viability and immunological status of ADMSCs, which may have implications for ADMSC-based cell therapies. Alterations in autophagy can affect numerous processes in MSCs, including the inhibition of tissue regeneration as well as pathological differentiation.
Topics: Humans; Herpesvirus 1, Human; Herpes Simplex; Mesenchymal Stem Cells; Herpesvirus 2, Human; Cytokines; Inflammation
PubMed: 37569367
DOI: 10.3390/ijms241511989