To investigate the epidemiology of herpes simplex virus type 1 (HSV-1) in Latin America and the Caribbean.
Systematic review and meta-analytics guided by the Cochrane Collaboration Handbook and ...reported following the PRISMA guidelines.
Thirty-three relevant reports were identified including 35 overall (and 95 stratified) seroprevalence measures, and five and nine proportions of virus isolation in genital ulcer disease (GUD) and in genital herpes, respectively. Pooled mean seroprevalence was 57.2% (95% CI: 49.7-64.6%) among children and 88.4% (95% CI: 85.2-91.2%) among adults. Pooled mean seroprevalence was lowest at 49.7% (95% CI: 42.8-56.6%) in those aged ≤10, followed by 77.8% (95% CI: 67.9-84.8%) in those aged 10-20, 82.8% (95% CI: 73.1-90.8%) in those aged 20-30, 92.5% (95% CI: 89.4-95.1%) in those aged 30-40, and 94.2% (95% CI: 92.7-95.5%) in those aged ≥40. Age was the strongest source of heterogeneity in seroprevalence, explaining 54% of variation. Evidence was found for seroprevalence decline over time. Pooled mean proportion of HSV-1 isolation was 0.9% (95% CI: 0.0-3.6%) in GUD and 10.9% (95% CI: 4.4-19.4%) in genital herpes.
HSV-1 is a widely prevalent infection in this region, but its epidemiology may be slowly transitioning, with still limited contribution for HSV-1 in genital herpes.
Toll-like receptors (TLRs) are fundamental sensor molecules of the host innate immune system, which detect conserved molecular signatures of a wide range of microbial pathogens and initiate innate ...immune responses via distinct signaling pathways. Various TLRs are implicated in the early interplay of host cells with invading viruses, which regulates viral replication and/or host responses, ultimately impacting on viral pathogenesis. To survive the host innate defense mechanisms, many viruses have developed strategies to evade or counteract signaling through the TLR pathways, creating an advantageous environment for their propagation. Here we review the current knowledge of the roles TLRs play in antiviral innate immune responses, discuss examples of TLR-mediated viral recognition, and describe strategies used by viruses to antagonize the host antiviral innate immune responses.
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•TLRs are membrane-bound sensors that activate innate immune responses to viruses.•TLRs recognize viral proteins on cell surface or viral nucleic acids in endosomes.•TLRs employ distinct pathways to induce interferon (IFN) antiviral and/or inflammatory responses.•Viruses have evolved elaborate tactics to circumvent TLR-mediated innate immunity.•TLRs regulate viral pathogenesis and are amenable to therapeutic purposes.
Herpes simplex virus (HSV) infections of the central nervous system (CNS) are associated with significant morbidity and mortality rates in children. This study assessed the impact of a direct HSV ...(dHSV) PCR assay on the time to result reporting and the duration of acyclovir therapy for children with signs and symptoms of meningitis and encephalitis. A total of 363 patients with HSV PCR results from cerebrospinal fluid (CSF) samples were included in this retrospective analysis, divided into preimplementation and postimplementation groups. For the preimplementation group, CSF testing was performed using a laboratory-developed real-time PCR assay; for the postimplementation group, CSF samples were tested using a direct sample-to-answer assay. All CSF samples were negative for HSV. Over 60% of patients from both groups were prescribed acyclovir. The average HSV PCR test turnaround time for the postimplementation group was reduced by 14.5 h (23.6 h versus 9.1 h;
< 0.001). Furthermore, 79 patients (43.6%) in the postimplementation group had dHSV PCR results reported <4 h after specimen collection. The mean time from specimen collection to acyclovir discontinuation was 17.1 h shorter in the postimplementation group (31.1 h versus 14 h;
< 0.001). The median duration of acyclovir therapy was also significantly reduced in the postimplementation group (29.2 h versus 14.3 h;
= 0.01). Our investigation suggests that implementation of rapid HSV PCR testing can decrease turnaround times and the duration of unnecessary acyclovir therapy.
Herpes simplex virus (HSV) infection triggered n-methyl-D-aspartate (NMDA) encephalitis can lead to varied neuropsychiatric manifestations, including movement disorders and manic symptoms. HSV is ...known to affect the same brain regions as in secondary mania.
We present a 35-year-old female diagnosed with recurrent depressive disorder (RDD) who developed NMDA encephalitis triggered by HSV infection.
HSV-triggered NMDA encephalitis led to a manic switch in a woman with RDD on antidepressants, along with the new onset of dyskinetic movements.
A neurological insult predisposed our patient to the variable effects of antidepressant drugs.
Abstract Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future ...decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinct pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV.
Type I interferon (IFN) response is commonly recognized as the main signaling activity of STING. Here, we generate the Sting1S365A/S365A mutant mouse that precisely ablates IFN-dependent activities ...while preserving IFN-independent activities of STING. StingS365A/S365A mice protect against HSV-1 infection, despite lacking the STING-mediated IFN response. This challenges the prevailing view and suggests that STING controls HSV-1 infection through IFN-independent activities. Transcriptomic analysis reveals widespread IFN-independent activities of STING in macrophages and T cells, and STING activities in T cells are predominantly IFN independent. In mouse tumor models, T cells in the tumor experience substantial cell death that is in part mediated by IFN-independent activities of STING. We found that the tumor induces STING-mediated cell death in T cells to evade immune control. Our data demonstrate that mammalian STING possesses widespread IFN-independent activities that are important for restricting HSV-1 infection, tumor immune evasion and likely also adaptive immunity.
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•Sting-S365A mutation in mice specifically abrogates STING-mediated IFN signaling•STING has many IFN-independent activities that are physiologically important•STING restricts HSV-1 infection via IFN-independent activities•Tumor induces STING-mediated T cell death to evade immune control
Type I interferon response was commonly believed to be the major (if not the sole) signaling activity of STING. Wu et al. reveal that mammalian STING possesses widespread IFN-independent activities that are physiologically important for antiviral response, tumor immune evasion and likely also adaptive T cell immunity.
Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first ...step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (∼190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.
Viral encephalitis continues to be a significant public health concern. In our previous study, we discovered a lower expression of antiviral factors, such as IFN-β, STING and IFI16, in the brain ...tissues of patients with Rasmussen's encephalitis (RE), a rare chronic neurological disorder often occurred in children, characterized by unihemispheric brain atrophy. Furthermore, a higher cumulative viral score of human herpes viruses (HHVs) was also found to have a significant positive correlation with the unihemispheric atrophy in RE. Type I IFNs (IFN-I) signaling is essential for innate anti-infection response by binding to IFN-α/β receptor (IFNAR). In this study, we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1 (HSV-1) via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain lesions. While all mice exhibited typical viral encephalitis lesions in their brains, HSV-induced epilepsy was only observed in A6 mice. The gene expression matrix, functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced epilepsy. Additionally, ten key genes with the highest scores were identified. Taken together, these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions, thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.
•Mice with IFN-I signaling deficiency are prone to HSV-1 induced epilepsy.•Repression of IFN-I signaling promotes brain atrophy in RE and other HHVs encephalitis.•Intact IFN-I signaling significantly restricts HHVs-induced neural symptoms.
Efficacy Results of a Trial of a Herpes Simplex Vaccine Belshe, Robert B; Leone, Peter A; Bernstein, David I ...
New England journal of medicine/The New England journal of medicine,
01/2012, Letnik:
366, Številka:
1
Journal Article
Recenzirano
Odprti dostop
There is no vaccine to prevent herpes simplex virus (HSV) infection. In this trial in 8323 women, a candidate HSV vaccine containing glycoprotein D was found to be ineffective in preventing HSV-2 ...infection.
Both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can cause primary infection of the genital tract, and HSV-1 infection has become an increasingly frequent cause of genital disease.
1
The majority of HSV infections are asymptomatic, and only 10 to 25% of persons with HSV-2 antibodies have recurrent genital disease.
2
,
3
Transmission of HSV from infected women to neonates may lead to severe neurologic disease or death in the newborn. Strategies to control genital herpes infection and disease have mainly focused on antiviral chemotherapy, education, and the use of condoms. The availability of an effective prophylactic vaccine would . . .
In the process of generating herpes simplex virus 1 (HSV-1) mutations in the viral regulatory gene encoding infected cell protein 0 (ICP0), we isolated a viral mutant, termed KOS-NA, that was ...severely impaired for acute replication in the eyes and trigeminal ganglia (TG) of mice, defective in establishing a latent infection, and reactivated poorly from explanted TG. To identify the secondary mutation(s) responsible for the impaired phenotypes of this mutant, we sequenced the KOS-NA genome and noted that it contained two nonsynonymous mutations in
, which encodes the large subunit of ribonucleotide reductase, ICP6. These mutations resulted in lysine-to-proline (residue 393) and arginine-to-histidine (residue 950) substitutions in ICP6. To determine whether alteration of these amino acids was responsible for the KOS-NA phenotypes
, we recombined the wild-type UL39 gene into the KOS-NA genome and rescued its acute replication phenotypes in mice. To further establish the role of
in KOS-NA's decreased pathogenicity, the
mutations were recombined into HSV-1 (generating UL39
), and this mutant virus showed reduced ocular and TG replication in mice comparable to that of KOS-NA. Interestingly, ICP6 protein levels were reduced in KOS-NA-infected cells relative to the wild-type protein. Moreover, we observed that KOS-NA does not counteract caspase 8-induced apoptosis, unlike wild-type strain KOS. Based on alignment studies with other HSV-1 ICP6 homologs, our data suggest that amino acid 950 of ICP6 likely plays an important role in ICP6 accumulation and inhibition of apoptosis, consequently impairing HSV-1 pathogenesis in a mouse model of HSV-1 infection.
HSV-1 is a major human pathogen that infects ∼80% of the human population and can be life threatening to infected neonates or immunocompromised individuals. Effective therapies for treatment of recurrent HSV-1 infections are limited, which emphasizes a critical need to understand in greater detail the events that modulate HSV-1 replication and pathogenesis. In the current study, we identified a neuroattenuated HSV-1 mutant (i.e., KOS-NA) that contains novel mutations in the UL39 gene, which codes for the large subunit of ribonucleotide reductase (also known as ICP6). This mutant form of ICP6 was responsible for the attenuation of KOS-NA
and resulted in diminished ICP6 protein levels and antiapoptotic effect. Thus, we have determined that subtle alteration of the UL39 gene regulates expression and functions of ICP6 and severely impacts HSV-1 pathogenesis, potentially making KOS-NA a promising vaccine candidate against HSV-1.
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