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Advances in Pediatrics Aug 2022The herpes virus was named by the Greek physician Hippocrates who called it herpes because the lesions appeared near each other and were vesicular. Alphaherpesvirinae,... (Review)
Review
The herpes virus was named by the Greek physician Hippocrates who called it herpes because the lesions appeared near each other and were vesicular. Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae are subfamilies of the human herpes virus family. The Alphaherpesvirinae subfamily includes the simplex viruses-HSV-1 and HSV-2-and varicellovirus-varicella zoster virus. There are more than 200 members of the Herpesviridae family capable of infecting different species, 8 of which are known to cause disease in humans. The simplex viruses can cause lifelong genital infections, and despite the prevalence of HSV-1 and HSV-2 infections in the United States decreasing in the past 20 years, infections with these viruses continue to contribute to significant clinical and psychological morbidities.
Topics: Alphaherpesvirinae; Genitalia; Herpes Genitalis; Herpes Simplex; Humans; Simplexvirus; United States
PubMed: 35985707
DOI: 10.1016/j.yapd.2022.03.010 -
Current Opinion in Infectious Diseases Jun 2023The most common infectious etiologies of meningitis and encephalitis are viruses. In this review, we will discuss current epidemiology, prevention, diagnosis, and... (Review)
Review
PURPOSE OF REVIEW
The most common infectious etiologies of meningitis and encephalitis are viruses. In this review, we will discuss current epidemiology, prevention, diagnosis, and treatment of the most common causes of viral meningitis and encephalitis worldwide.
RECENT FINDINGS
Viral meningitis and encephalitis are increasingly diagnosed as molecular diagnostic techniques and serologies have become more readily available worldwide but recent progress in novel antiviral therapies remains limited. Emerging and re-emerging viruses that have caused endemic or worldwide outbreaks or epidemics are arboviruses (e.g., West Nile virus, Japanese encephalitis, Tick borne encephalitis, Dengue, Zika, Toscana), enteroviruses (e.g., Enterovirus 71, Enterovirus D68), Parechoviruses, respiratory viruses [e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, metapneumoviruses, measles, mumps], and herpes viruses [e.g., herpes simplex virus (HSV) type 1 (HSV-1), HSV-2, human herpes (HV) 6, varicella zoster virus (VZV)]. Future efforts should concentrate in increasing availability for those viruses with effective vaccination [e.g., Japanese encephalitis, Tick borne encephalitis, varicella zoster viruses, SARS-CoV-2, influenza], prompt initiation of those with encephalitis with treatable viruses (e.g., HSV-1, VZV), increasing the diagnostic yield by using novel techniques such as metagenomic sequencing and avoiding unnecessary antibiotics in those with viral meningitis or encephalitis.
SUMMARY
We review the current epidemiology, clinical presentation, diagnosis, and treatment of the common causative agents of viral meningitis and encephalitis worldwide.
Topics: Humans; Influenza, Human; COVID-19; SARS-CoV-2; Meningitis, Viral; Viruses; Encephalitis; Herpesvirus 3, Human; Herpesvirus 1, Human; Zika Virus; Zika Virus Infection
PubMed: 37093042
DOI: 10.1097/QCO.0000000000000922 -
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 -
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 -
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 -
Virologie (Montrouge, France) Oct 2020Central nervous system (CNS) infections caused by herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) greatly vary in frequency and severity. HSV-1 causes mostly herpes... (Review)
Review
Central nervous system (CNS) infections caused by herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) greatly vary in frequency and severity. HSV-1 causes mostly herpes simplex encephalitis (HSE) which represents 5% to 15% of infectious encephalitis in children and adults. Despite available molecular diagnosis tools and antiviral drugs, the prognosis of HSE remains unacceptably low. In addition to mortality and immediate sequelae, auto-immune encephalitis (AIE) may occur, associated with the development of anti-neuronal antibodies in 1/4 of cases. Replicative relapses have been associated in few cases with genetic defects altering the innate immune response of neuronal cells. Herpetic meningitis is frequent, mostly associated with HSV-2 and genital herpes, sometimes recurrent and, mostly benign, except in immunocompromised individuals. Finally, exceptional cases of myelitis have been reported, due to ascending propagation of HSV-2 in the CNS. This review does not include neonatal infections.
Topics: Adult; Child; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Meningitis; Myelitis
PubMed: 33111702
DOI: 10.1684/vir.2020.0862 -
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 -
Cells Apr 2022The innate immune system provides the first line of defense against cellular perturbations. Innate immune activation elicits inflammatory programmed cell death in... (Review)
Review
It's All in the PAN: Crosstalk, Plasticity, Redundancies, Switches, and Interconnectedness Encompassed by PANoptosis Underlying the Totality of Cell Death-Associated Biological Effects.
The innate immune system provides the first line of defense against cellular perturbations. Innate immune activation elicits inflammatory programmed cell death in response to microbial infections or alterations in cellular homeostasis. Among the most well-characterized programmed cell death pathways are pyroptosis, apoptosis, and necroptosis. While these pathways have historically been defined as segregated and independent processes, mounting evidence shows significant crosstalk among them. These molecular interactions have been described as 'crosstalk', 'plasticity', 'redundancies', 'molecular switches', and more. Here, we discuss the key components of cell death pathways and note several examples of crosstalk. We then explain how the diverse descriptions of crosstalk throughout the literature can be interpreted through the lens of an integrated inflammatory cell death concept, PANoptosis. The totality of biological effects in PANoptosis cannot be individually accounted for by pyroptosis, apoptosis, or necroptosis alone. We also discuss PANoptosomes, which are multifaceted macromolecular complexes that regulate PANoptosis. We consider the evidence for PANoptosis, which has been mechanistically characterized during influenza A virus, herpes simplex virus 1, , and infections, as well as in response to altered cellular homeostasis, in inflammatory diseases, and in cancers. We further discuss the role of IRF1 as an upstream regulator of PANoptosis and conclude by reexamining historical studies which lend credence to the PANoptosis concept. Cell death has been shown to play a critical role in infections, inflammatory diseases, neurodegenerative diseases, cancers, and more; therefore, having a holistic understanding of cell death is important for identifying new therapeutic strategies.
Topics: Apoptosis; Cell Death; Herpesvirus 1, Human; Necroptosis; Pyroptosis
PubMed: 35563804
DOI: 10.3390/cells11091495