Development and validation of a fully automated laboratory-developed test for detection of HSV-1/2 and VZV in clinical samples run on the Panther Fusion® system.

The purpose of this study was to develop a laboratory developed test (LDT) for HSV1/2 and VZV to run on fully automated Hologic Panther Fusion® System. The Panther Fusion System is a fully automated walkaway system, providing end-to-end workflow from sample input to DNA/RNA extraction, amplification, automated analysis, and reporting to a laboratory information system (LIS). The LDT was developed and validated on 230 clinical and 20 reference samples (n = 250) and compared to a commercially available kit. Assessment of the analytical and diagnostic performances of the LDT revealed >98% accuracy, sensitivity, and specificity, which is consistent with or better than many of the commercial or laboratory-developed tests available. The advantage of this LDT is that it is designed to perform a single-run full female health screening in parallel with 4 commercially available Hologic kits for Chlamydia trachomatis/Neisseria gonorrhea (CT/NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), and bacterial vaginosis (BV).

Is there a role for herpes simplex virus type 1 in multiple sclerosis?

Numerous studies relate the onset and severity of multiple sclerosis (MS) with viral infections. Herpes simplex virus type 1 (HSV-1), which is neurotropic and highly prevalent in the brain of healthy individuals, has been proposed to relate to MS. Here, we review and discuss the reported connections between HSV-1 and MS.

Pluronic F127-tailored lecithin organogel of acyclovir: preclinical evidence of antiviral activity using BALB/c murine model of cutaneous HSV-1 infection.

Herpes is a well-known contagious infection equally affecting both sexes. Among many antiviral drugs employed for its treatment, acyclovir (ACY) is the drug of choice. The currently available therapies of ACY suffer from limitations like poor oral bioavailability (10-15%) and high-dose requirement. The present scientific study aims to explore pluronic lecithin organogel (PLO) as a novel drug delivery platform for ACY to bring an improvement in its delivery through topical route. The properties of organogel like biocompatibility and amphiphilic nature which facilitates dissolution of various drugs of different solubility characteristics along with enhancing the permeation potential of active molecules make it a favorable drug delivery platform for the management of topical diseases. The developed PLO formulations were characterized for micromeritic characteristics, viz., zeta potential, percentage drug content, organogel morphology, skin permeation, retention, and stability studies. The selected topical formulation was further compared with the marketed one for its therapeutic efficacy by inducing cutaneous Herpes simplex virus type 1 infection followed by confirmation of viral load by immunofluorescence and PCR analyses. The developed formulation showed significant improvement over the marketed product as reflected in lesion scoring index and PCR analysis. Further, it proved better to the marketed formulation in t.i.d. treatment regimen in comparison to control. The improvement in overall performance leading to enhanced bioavailability and safety is attributed to the synergism between excipient properties and formulation characteristics. The drug ACY in this micro environment not only finds an improved delivery vehicle but it also offers enhanced drug-target interactions.

Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas.

Glioblastoma multiforme (GBM) represents one of the most challenging malignancies due to many factors including invasiveness, heterogeneity, and an immunosuppressive microenvironment. Current treatment modalities have resulted in only modest effect on outcomes. The development of viral vectors for oncolytic immunovirotherapy and targeted drug delivery represents a promising therapeutic prospect for GBM and other brain tumors. A host of genetically engineered viruses, herpes simplex virus, poliovirus, measles, and others, have been described and are at various stages of clinical development. Herein we provide a review of the advances and current state of oncolytic virotherapy for the targeted treatment of GBM and malignant gliomas.

Pathogenesis of Herpes Stromal Keratitis: Immune Inflammatory Response Mediated by Inflammatory Regulators.

Herpes stromal keratitis (HSK) is one of the primary diseases that cause vision loss or even blindness after herpes simplex virus (HSV)-1 infection. HSK-associated vision impairment is predominantly due to corneal scarring and neovascularization caused by inflammation. In the infected cornea, HSV can activate innate and adaptive immune responses of host cells, which triggers a cascade of reactions that leads to the release of inflammatory cytokines, chemokines, microRNA, and other regulatory factors that have stimulating or inhibitory effects on tissue. Physiologically, host cells show homeostasis. In this review, we summarize the factors involved in HSK pathogenesis from the perspective of immunity, molecules, and pathological angiogenesis. We also describe in detail the pathogenesis of chronic inflammatory lesions of the corneal stroma in response to HSV-1 infection.

Herpes simplex virus type 1 infection in neurons leads to production and nuclear localization of APP intracellular domain (AICD): implications for Alzheimer's disease pathogenesis.

Several data indicate that neuronal infection with herpes simplex virus type 1 (HSV-1) causes biochemical alterations reminiscent of Alzheimer's disease (AD) phenotype. They include accumulation of amyloid-ß (Aß), which originates from the cleavage of amyloid precursor protein (APP), and hyperphosphorylation of tau protein, which leads to neurofibrillary tangle deposition. HSV-1 infection triggers APP processing and drives the production of several fragments including APP intracellular domain (AICD) that exerts transactivating properties. Herein, we analyzed the production and intracellular localization of AICD following HSV-1 infection in neurons. We also checked whether AICD induced the transcription of two target genes, neprilysin (nep) and glycogen synthase kinase 3ß (gsk3ß), whose products play a role in Aß clearance and tau phosphorylation, respectively. Our data indicate that HSV-1 led to the accumulation and nuclear translocation of AICD in neurons. Moreover, results from chromatin immunoprecipitation assay showed that AICD binds the promoter region of both nep and gsk3ß. Time course analysis of NEP and GSK3ß expression at both mRNA and protein levels demonstrated that they are differently modulated during infection. NEP expression and enzymatic activity were initially stimulated but, with the progression of infection, they were down-regulated. In contrast, GSK3ß expression remained nearly unchanged, but the analysis of its phosphorylation suggests that it was inactivated only at later stages of HSV-1 infection. Thus, our data demonstrate that HSV-1 infection induces early upstream events in the cell that may eventually lead to Aß deposition and tau hyperphosphorylation and further suggest HSV-1 as a possible risk factor for AD.

Host Cell Protein C9orf9 Promotes Viral Proliferation via Interaction with HSV-1 UL25 Protein / 中国病毒学·英文版

In light of the scarcity of reports on the interaction between HSV-1 nucleocapsid protein UL25 and its host cell proteins,the purpose of this study is to use yeast two-hybrid screening to search for cellular proteins that can interact with the UL25 protein.C9orf69,a protein of unknown function was identified.The interaction between the two proteins under physiological conditions was also confirmed by biological experiments including co-localization by fluorescence and immunoprecipitation.A preliminary study of the function of C9orf69 showed that it promotes viral proliferation.Further studies showed that C9orf69 did not influence viral multiplication efficiency by transcriptional regulation of viral genes,but indirectly promoted proliferation via interaction with UL25.