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The Journal of Infectious Diseases Sep 2018Varicella-zoster virus (VZV) causes clinically significant illness during acute and recurrent infection accompanied by robust innate and acquired immune responses.... (Review)
Review
Varicella-zoster virus (VZV) causes clinically significant illness during acute and recurrent infection accompanied by robust innate and acquired immune responses. Innate immune cells in skin and ganglion secrete type I interferon (IFN-I) and proinflammatory cytokines to control VZV. Varicella-zoster virus subverts pattern recognition receptor sensing to modulate antigen presentation and IFN-I production. During primary infection, VZV hijacks T cells to disseminate to the skin and establishes latency in ganglia. Durable T- and B-cell memory formed within a few weeks of infection is boosted by reactivation or re-exposure. Antigen-specific T cells are recruited and potentially retained in VZV-infected skin to counteract reactivation. In latently VZV-infected ganglia, however, virus-specific T cells have not been recovered, suggesting that local innate immune responses control VZV latency. Antibodies prevent primary VZV infection, whereas T cells are fundamental to resolving disease, limiting severity, and preventing reactivation. In this study, we review current knowledge on the interactions between VZV and the human immune system.
Topics: Adaptive Immunity; Herpesvirus 3, Human; Humans; Immunity, Cellular; Immunity, Humoral; Immunity, Innate; Varicella Zoster Virus Infection
PubMed: 30247598
DOI: 10.1093/infdis/jiy403 -
International Journal of Molecular... Aug 2020Herpes simplex virus type 1 (HSV-1) is a structurally complex enveloped dsDNA virus that has evolved to replicate in human neurons and epithelia. Viral gene expression,... (Review)
Review
Herpes simplex virus type 1 (HSV-1) is a structurally complex enveloped dsDNA virus that has evolved to replicate in human neurons and epithelia. Viral gene expression, DNA replication, capsid assembly, and genome packaging take place in the infected cell nucleus, which mature nucleocapsids exit by envelopment at the inner nuclear membrane then de-envelopment into the cytoplasm. Once in the cytoplasm, capsids travel along microtubules to reach, dock, and envelope at cytoplasmic organelles. This generates mature infectious HSV-1 particles that must then be sorted to the termini of sensory neurons, or to epithelial cell junctions, for spread to uninfected cells. The focus of this review is upon our current understanding of the viral and cellular molecular machinery that enables HSV-1 to travel within infected cells during egress and to manipulate cellular organelles to construct its envelope.
Topics: Animals; Herpes Simplex; Herpesvirus 1, Human; Host-Pathogen Interactions; Humans; Viral Envelope; Virus Release
PubMed: 32825127
DOI: 10.3390/ijms21175969 -
Frontiers in Cellular and Infection... 2019Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) have co-evolved with humans for thousands of years and are present at a high prevalence in the population... (Review)
Review
Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) have co-evolved with humans for thousands of years and are present at a high prevalence in the population worldwide. HSV infections are responsible for several illnesses including skin and mucosal lesions, blindness and even life-threatening encephalitis in both, immunocompetent and immunocompromised individuals of all ages. Therefore, diseases caused by HSVs represent significant public health burdens. Similar to other herpesviruses, HSV-1 and HSV-2 produce lifelong infections in the host by establishing latency in neurons and sporadically reactivating from these cells, eliciting recurrences that are accompanied by viral shedding in both, symptomatic and asymptomatic individuals. The ability of HSVs to persist and recur in otherwise healthy individuals is likely given by the numerous virulence factors that these viruses have evolved to evade host antiviral responses. Here, we review and discuss molecular mechanisms used by HSVs to evade early innate antiviral responses, which are the first lines of defense against these viruses. A comprehensive understanding of how HSVs evade host early antiviral responses could contribute to the development of novel therapies and vaccines to counteract these viruses.
Topics: Herpesvirus 1, Human; Herpesvirus 2, Human; Host-Pathogen Interactions; Humans; Immune Evasion
PubMed: 31114761
DOI: 10.3389/fcimb.2019.00127 -
Trends in Microbiology Oct 2020Herpes simplex virus-1 (HSV-1) establishes latency preferentially in sensory neurons of peripheral ganglia. A variety of stresses can induce recurrent reactivations of... (Review)
Review
Herpes simplex virus-1 (HSV-1) establishes latency preferentially in sensory neurons of peripheral ganglia. A variety of stresses can induce recurrent reactivations of the virus, which spreads and then actively replicates to the site of primary infection (usually the lips or eyes). Viral particles produced following reactivation can also reach the brain, causing a rare but severe form of diffuse acute infection, namely herpes simplex encephalitis. Most of the time, this infection is clinically asymptomatic. However, it was recently correlated with the production and accumulation of neuropathological biomarkers of Alzheimer's disease. In this review we discuss the different cellular and molecular mechanisms underlying the acute and long-term damage caused by HSV-1 infection in the brain.
Topics: Animals; Brain; Brain Diseases; Herpes Simplex; Herpesvirus 1, Human; Humans
PubMed: 32386801
DOI: 10.1016/j.tim.2020.03.003 -
Viruses Feb 2023Herpes simplex virus (HSV) and varicella zoster virus (VZV) are alpha herpesviruses that establish life-long latent infection in neuronal ganglia after primary... (Review)
Review
Herpes simplex virus (HSV) and varicella zoster virus (VZV) are alpha herpesviruses that establish life-long latent infection in neuronal ganglia after primary infection. Periodic reactivation of these viruses results in recurrent infections that can have significant impact on patients' quality of life. HSV commonly causes oral and genital mucocutaneous infections whereas VZV is responsible for varicella/chickenpox and herpes zoster/shingles, but cancer patients are at particularly higher risk of complications including disseminated and visceral infections due to impaired cell-mediated immunity. While diagnosis of more common HSV and/or VZV infections is frequently clinically based, immunocompromised hosts may have atypical skin presentation or visceral involvement. Thus, diagnostic confirmation using virus-specific tests such as polymerase chain reaction or immunohistochemical staining is crucial in some cases. Oral acyclovir, valacyclovir and famciclovir are usually used for mild to moderate infections and intravenous acyclovir is the drug of choice for severe or disseminated infections. Foscarnet can be used when acyclovir-resistance is confirmed or suspected. Pharmaceutical prophylaxis against HSV and/or VZV should be considered in high-risk cancers patients. Currently, there is no commercially available vaccine against HSV, but VZV vaccines are available to prevent varicella and zoster.
Topics: Humans; Chickenpox; Herpesvirus 3, Human; Simplexvirus; Quality of Life; Herpes Zoster; Varicella Zoster Virus Infection; Acyclovir; Neoplasms
PubMed: 36851652
DOI: 10.3390/v15020439 -
Viruses Jun 2023Herpes simplex virus-1 (HSV-1) and -2 (HSV-2) are large, spherically shaped, double-stranded DNA viruses that coevolved with for over 300,000 years, having developed... (Review)
Review
Herpes simplex virus-1 (HSV-1) and -2 (HSV-2) are large, spherically shaped, double-stranded DNA viruses that coevolved with for over 300,000 years, having developed numerous immunoevasive mechanisms to survive the lifetime of their human host. Although in the continued absence of an acceptable prophylactic and therapeutic vaccine, approved pharmacologics (e.g., nucleoside analogs) hold benefit against viral outbreaks, while resistance and toxicity limit their universal application. Against these shortcomings, there is a long history of proven and unproven home remedies. With the breadth of purported alternative therapies, patients are exposed to risk of harm without proper information. Here, we examined the shortcomings of the current gold standard HSV therapy, acyclovir, and described several natural products that demonstrated promise in controlling HSV infection, including lemon balm, lysine, propolis, vitamin E, and zinc, while arginine, cannabis, and many other recreational drugs are detrimental. Based on this literature, we offered recommendations regarding the use of such natural products and their further investigation.
Topics: Humans; Antiviral Agents; Acyclovir; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Biological Products
PubMed: 37376614
DOI: 10.3390/v15061314 -
Biochemistry. Biokhimiia Dec 2014WHO reports that 90% of human population is infected by different types of herpesviruses, which develop latency or cause oral and genital herpes, conjunctivitis, eczema... (Review)
Review
WHO reports that 90% of human population is infected by different types of herpesviruses, which develop latency or cause oral and genital herpes, conjunctivitis, eczema herpeticum, and other diseases. Herpesvirus almost always accompanies HIV-infection and complicates AIDS treatment. Herpes simplex virus type 1 is one of the most wide spread viruses from the Herpesviridae family. HSV virion, genome structure, replication mechanisms, antiherpes drug development strategies, including design of prodrugs, and mutations causing ACV-resistance in clinical HSV isolates are discussed in this review.
Topics: Antiviral Agents; Drug Resistance, Viral; Genome, Viral; Herpesvirus 1, Human; Humans; Virion; Virus Replication
PubMed: 25749169
DOI: 10.1134/S0006297914130124 -
Current Issues in Molecular Biology 2021Prophylactic and therapeutic vaccines for the alphaherpesviruses including varicella zoster virus (VZV) and herpes simplex virus types 1 and 2 have been the focus of... (Review)
Review
Prophylactic and therapeutic vaccines for the alphaherpesviruses including varicella zoster virus (VZV) and herpes simplex virus types 1 and 2 have been the focus of enormous preclinical and clinical research. A live viral vaccine for prevention of chickenpox and a subunit therapeutic vaccine to prevent zoster are highly successful. In contrast, progress towards the development of effective prophylactic or therapeutic vaccines against HSV-1 and HSV-2 has met with limited success. This review provides an overview of the successes and failures, the different types of immune responses elicited by various vaccine modalities, and the need to reconsider the preclinical models and immune correlates of protection against HSV.
Topics: Alphaherpesvirinae; Animals; Herpesviridae Infections; Humans; Immunity; Vaccines, Attenuated; Vaccines, Subunit; Viral Vaccines
PubMed: 32963118
DOI: 10.21775/cimb.041.469 -
Autophagy Aug 2022Alphaherpesvirus infection results in severe health consequences in a wide range of hosts. USPs are the largest subfamily of deubiquitinating enzymes that play critical...
Alphaherpesvirus infection results in severe health consequences in a wide range of hosts. USPs are the largest subfamily of deubiquitinating enzymes that play critical roles in immunity and other cellular functions. To investigate the role of USPs in alphaherpesvirus replication, we assessed 13 USP inhibitors for PRV replication. Our data showed that all the tested compounds inhibited PRV replication, with the USP14 inhibitor b-AP15 exhibiting the most dramatic effect. Ablation of USP14 also influenced PRV replication, whereas replenishment of USP14 in null cells restored viral replication. Although inhibition of USP14 induced the K63-linked ubiquitination of PRV VP16 protein, its degradation was not dependent on the proteasome. USP14 directly bound to ubiquitin chains on VP16 through its UBL domain during the early stage of viral infection. Moreover, USP14 inactivation stimulated EIF2AK3/PERK- and ERN1/IRE1-mediated signaling pathways, which were responsible for VP16 degradation through SQSTM1/p62-mediated selective macroautophagy/autophagy. Ectopic expression of non-ubiquitinated VP16 fully rescued PRV replication. Challenge of mice with b-AP15 activated ER stress and autophagy and inhibited PRV infection . Our results suggested that USP14 was a potential therapeutic target to treat alphaherpesvirus-induced infectious diseases. ATF4: activating transcription factor 4; ATF6: activating transcription factor 6; ATG5: autophagy related 5; ATG12: autophagy related 12; CCK-8: cell counting kit-8; Co-IP: co-immunoprecipitation; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR associated system 9; DDIT3/CHOP: DNA-damage inducible transcript 3; DNAJB9/ERdj4: DnaJ heat shock protein family (Hsp40) member B9; DUBs: deubiquitinases; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EP0: ubiquitin E3 ligase ICP0; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; FOXO1: forkhead box O1; FRET: Förster resonance energy transfer; HSPA5/BiP: heat shock protein 5; HSV: herpes simplex virus; IE180: transcriptional regulator ICP4; MAP1LC3/LC3: microtube-associated protein 1 light chain 3; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; PPP1R15A/GADD34: protein phosphatase 1, regulatory subunit 15A; PRV: pseudorabies virus; PRV gB: PRV glycoprotein B; PRV gE: PRV glycoprotein E; qRT-PCR: quantitative real-time polymerase chain reaction; sgRNA: single guide RNA; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID: tissue culture infective dose; UB: ubiquitin; UBA: ubiquitin-associated domain; UBL: ubiquitin-like domain; UL9: DNA replication origin-binding helicase; UPR: unfolded protein response; USPs: ubiquitin-specific proteases; VHS: virion host shutoff; VP16: viral protein 16; XBP1: X-box binding protein 1; XBP1s: small XBP1; XBP1(t): XBP1-total.
Topics: Alphaherpesvirinae; Animals; Autophagy; Cell Proliferation; Endoplasmic Reticulum Stress; Herpes Simplex Virus Protein Vmw65; Macroautophagy; Mice; Sequestosome-1 Protein; Ubiquitin Thiolesterase
PubMed: 34822318
DOI: 10.1080/15548627.2021.2002101 -
Autophagy Dec 2023STING1 (stimulator of interferon response cGAMP interactor 1) plays an essential role in immune responses for virus inhibition via inducing the production of type I...
STING1 (stimulator of interferon response cGAMP interactor 1) plays an essential role in immune responses for virus inhibition via inducing the production of type I interferon, inflammatory factors and macroautophagy/autophagy. In this study, we found that STING1 activation could induce not only canonical autophagy but also non-canonical autophagy (NCA) which is independent of the ULK1 or BECN1 complexes to form MAP1LC3/LC3-positive structures. Whether STING1-induced NCA has similar characters and physiological functions to canonical autophagy is totally unknown. Different from canonical autophagy, NCA could increase single-membrane structures and failed to degrade long-lived proteins, and could be strongly suppressed by interrupting vacuolar-type H-translocating ATPase (V-ATPase) activity. Importantly, STING1-induced NCA could effectively inhibit DNA virus HSV-1 in cell model. Moreover, STING1 [1-340], a STING1 mutant lacking immunity and inflammatory response due to deletion of the tail end of STING1, could degrade virus through NCA alone, suggesting that the antiviral effect of activated STING1 could be separately mediated by inherent immunity, canonical autophagy, and NCA. In addition, the translocation and dimerization of STING1 do not rely on its immunity function and autophagy pathway. Similar to canonical autophagy, LC3-positive structures of NCA induced by STING1 could finally fuse with lysosomes, and the degradation of HSV-1 could be reverted by inhibition of lysosome function, suggesting that the elimination of DNA virus via NCA still requires the lysosome pathway. Collectively, we proved that besides its classical immunity function and canonical autophagy pathway, STING1-induced NCA is also an efficient antiviral pathway for the host cell. ATG: autophagy related; Baf: bafilomycin A; CASM: conjugation of LC3 to a single membrane; CGAS: cyclic GMP-AMP synthase; cGAMP: cyclic GMP-AMP; CQ: chloroquine; CTD: C-terminal domain; CTT: C-terminal tail; ER: endoplasmic reticulum; ERGIC: ER-Golgi intermediate compartment; HSV-1: herpes simplex virus 1; IRF3: interferon regulatory factor 3; IFNs: interferons; LAMP1: lysosomal associated membrane protein 1; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; RB1CC1/FIP200: RB1 inducible coiled-coil 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TGOLN2/TGN46: trans-golgi network protein 2; ULK1: unc-51 like autophagy activating kinase 1; V-ATPase: vacuolar-type H-translocating ATPase; VSV: vesicular stomatitis virus.
Topics: Autophagy; Herpesvirus 1, Human; Proteins; Interferons; Antiviral Agents; Adenosine Triphosphatases
PubMed: 37471002
DOI: 10.1080/15548627.2023.2237794