The study investigated the inhibitory effect and mechanism of tectorigenin derivative(SGY) against herpes simplex virus type Ⅰ(HSV-1) by in vitro experiments. The cytotoxicity of SGY and positive drug acyclovir(ACV) on African green monkey kidney(Vero) cells and mouse microglia(BV-2) cells was detected by cell counting kit-8(CCK-8) method, and the maximum non-toxic concentration and median toxic concentration(TC_(50)) of the drugs were calculated. After Vero cells were infected with HSV-1, the virulence was determined by cytopathologic effects(CPE) to calculate viral titers. The inhibitory effect of the tested drugs on HSV-1-induced cytopathy in Vero cells was measured, and their modes of action were initially explored by virus adsorption, replication and inactivation. The effects of the drugs on viral load of BV-2 cells 24 h after HSV-1 infection and the Toll-like receptor(TLR) mRNA expression were detected by real-time fluorescence quantitative PCR(RT-qPCR). The maximum non-toxic concentrations of SGY against Vero and BV-2 cells were 382.804 μg·mL~(-1) and 251.78 μg·mL~(-1), respectively, and TC_(50) was 1 749.98 μg·mL~(-1) and 2 977.50 μg·mL~(-1), respectively. In Vero cell model, the half maximal inhibitory concentration(IC_(50)) of SGY against HSV-1 was 54.49 μg·mL~(-1), and the selection index(SI) was 32.12, with the mode of action of significantly inhibiting replication and directly inactivating HSV-1. RT-qPCR results showed that SGY markedly reduced the viral load in cells. The virus model group had significantly increased relative expression of TLR2, TLR3 and tumor necrosis factor receptor-associated factor 3(TRAF3) and reduced relative expression of TLR9 as compared with normal group, and after SGY intervention, the expression of TLR2, TLR3 and TRAF3 was decreased to different degrees and that of TLR9 was enhanced. The expression of inflammatory factors inducible nitric oxide synthase(iNOS), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) was remarkably increased in virus model group as compared with that in normal group, and the levels of these inflammatory factors dropped after SGY intervention. In conclusion, SGY significantly inhibited and directly inactivated HSV-1 in vitro. In addition, it modulated the expression of TLR2, TLR3 and TLR9 related pathways, and suppressed the increase of inflammatory factor levels.
Animals ; Antiviral Agents/therapeutic use* ; Chlorocebus aethiops ; Herpes Simplex/pathology* ; Herpesvirus 1, Human/metabolism* ; Isoflavones ; Mice ; TNF Receptor-Associated Factor 3/pharmacology* ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 3/metabolism* ; Toll-Like Receptor 9/metabolism* ; Toll-Like Receptors/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Vero Cells ; Virus Replication

Child ; Corpus Callosum ; pathology ; Encephalitis, Herpes Simplex ; pathology ; Humans ; Magnetic Resonance Imaging ; methods ; Male

Herpes simplex virus (HSV) is a recognized cause of gastrointestinal infection in immunodeficient patients. Although a few cases of HSV gastritis and colitis in immunocompromised patients have been reported, there are no reports of HSV duodenitis in patients with Crohn's disease (CD). A 74-year-old female was admitted with general weakness and refractory epigastric pain. She had been diagnosed with CD three years ago. Esophagogastroduodenoscopy (EGD) revealed diffuse edematous and whitish mucosa with multiple erosions in the duodenum. Considering the possibility of viral co-infection, cytomegalovirus (CMV) immunohistochemical staining, PCR, and cultures of duodenal biopsies were performed, all of which were negative with the exception of the isolation of HSV in culture. After administration of intravenous acyclovir for 1 week, follow-up EGD showed almost complete resolution of the lesions and the patient's symptoms improved. In CD patients with refractory gastrointestinal symptoms, HSV, as well as CMV, should be considered as a possible cause of infection, so that the diagnosis of viral infection is not delayed and the appropriate antiviral treatment can be initiated.
Acyclovir/therapeutic use ; Aged ; Antiviral Agents/therapeutic use ; Crohn Disease/complications/*diagnosis/virology ; DNA, Viral/analysis ; Duodenitis/complications/*diagnosis ; Endoscopy, Digestive System ; Female ; Herpes Simplex/*diagnosis/drug therapy/virology ; Humans ; Intestinal Mucosa/pathology ; Polymerase Chain Reaction ; Simplexvirus/genetics/*isolation & purification

Initial skirmishes between the host and pathogen result in spillage of the contents of the bacterial cell. Amongst the spillage, the secondary messenger molecule, cyclic dimeric guanosine monophosphate (c di-GMP), was recently shown to be bound by stimulator of interferon genes (STING). Binding of c di-GMP by STING activates the Tank Binding Kinase (TBK1) mediated signaling cascades that galvanize the body's defenses for elimination of the pathogen. In addition to c di-GMP, STING has also been shown to function in innate immune responses against pathogen associated molecular patterns (PAMPs) originating from the DNA or RNA of pathogens. The pivotal role of STING in host defense is exemplified by the fact that STING(-/-) mice die upon infection by HSV-1. Thus, STING plays an essential role in innate immune responses against pathogens. This opens up an exciting possibility of targeting STING for development of adjuvant therapies to boost the immune defenses against invading microbes. Similarly, STING could be targeted for mitigating the inflammatory responses augmented by the innate immune system. This review summarizes and updates our current understanding of the role of STING in innate immune responses and discusses the future challenges in delineating the mechanism of STING-mediated responses.
Animals ; Cyclic GMP ; physiology ; Dimerization ; Herpes Simplex ; immunology ; pathology ; Humans ; Immunity, Innate ; Membrane Proteins ; chemistry ; genetics ; metabolism ; Protein Binding ; RNA, Viral ; metabolism ; STAT6 Transcription Factor ; metabolism ; Second Messenger Systems

Oesophageal ulcerations are generally rare occurrences that are most commonly associated with gastro-oesophageal reflux disorder. Other causes include medications and infections in immunocompromised patients. Among the medications used in daily practice, doxycycline is most commonly implicated. Multiple aetiologies are generally uncommon. We report a case of mid-oesophageal ulcerations secondary to doxycycline and herpes simplex virus infection in an immunocompetent patient.
Anti-Bacterial Agents ; adverse effects ; Doxycycline ; adverse effects ; Endoscopy, Gastrointestinal ; Esophageal Diseases ; etiology ; pathology ; Esophagus ; pathology ; virology ; Female ; Herpes Simplex ; complications ; Humans ; Middle Aged ; Ulcer ; etiology ; pathology

Reports of combined candidal and herpetic esophagitis in immunocompetent states are rare and sporadic. A 44-year-old previously healthy lady presented with a one week history of progressive dysphagia, odynophagia and fever. Esophagogastroduodenoscopy (EGD) showed extensive desquamation of the entire esophagus except for distal 4 cm. Histopathological examination revealed ulcerated and inflamed squamous epithelium with the margin of ulcer showing a few overhanging squamous cells with dense eosinophilic cytoplasm, multinucleated and faceted nuclei with glassy chromatin, and an occasional Cowdry type A intranuclear inclusion bodies. Few candidal spores were seen in the underlying stroma. Intravenous acyclovir, fluconazole and pantoprazole were initiated. Oral analgesics were given for pain relief. She was treated for a total of 14 days. She showed significant improvement and was tolerating oral intake after discharge. The patient was asymptomatic with no evidence of recurrence at a 2-month follow-up.
Adult ; Antifungal Agents ; therapeutic use ; Antiviral Agents ; therapeutic use ; Candidiasis ; diagnosis ; drug therapy ; microbiology ; Esophagitis ; diagnosis ; drug therapy ; microbiology ; virology ; Esophagus ; microbiology ; pathology ; virology ; Female ; Herpes Simplex ; diagnosis ; drug therapy ; virology ; Humans ; Inclusion Bodies, Viral ; Spores, Fungal ; Treatment Outcome

The high signal intensities in bilateral mesiotemporal lobes on T2-weighted images are typical findings of herpes encephalitis or paraneoplastic limbic encephalitis. We report a case of neurosyphilis with mesiotemporal involvement on MRI. Positive antibodies in the cerebrospinal fluid confirmed the diagnosis. The results suggest that neurosyphilis should be considered when MRI results indicate mesiotemporal abnormalities.
Adult ; Anti-Bacterial Agents/administration & dosage ; Biopsy, Needle ; Chancre/diagnosis/pathology ; Diagnosis, Differential ; Encephalitis, Herpes Simplex/diagnosis ; Follow-Up Studies ; Humans ; Limbic Encephalitis/diagnosis ; Magnetic Resonance Imaging/*methods ; Male ; Neurosyphilis/*diagnosis/drug therapy/pathology ; Penicillins/administration & dosage ; Rare Diseases ; Temporal Lobe/*pathology ; Tongue/pathology

Aged ; Aged, 80 and over ; Esophagus ; pathology ; virology ; Herpes Simplex ; diagnosis ; genetics ; pathology ; Humans ; In Situ Hybridization ; Male ; Middle Aged ; Simplexvirus ; genetics

OBJECTIVETo establish an animal model of Bell's palsy induced by the reactivation of latent herpes simplex virus type 1 (HSV-1), and observe the effect of interferon and IgG on the facial nerve paralysis induced by HSV-1 infection. METHODS Totally 64 four-week-old female Balb/c mice weighted 16-18 gram were selected. Using scratching the surface of bilateral auricles by a 26-gauge needle, 25 microl HSV-1 with a titer of 6.7 x 10(8) PFU/ml was inoculated into the left auricle and the same volume of PBS was placed in the right in order to develop a mouse model of latent HSV-1. In this study, interferon and IgG administration were performed before and after facial nerve paralysis and continued for 3 days. Controls were given normal sodium instead of interferon and IgG, and the incidence and duration of facial nerve paralysis were compared in the groups interferon and IgG and control. Ciclosporin was given to the mice eight weeks after recovery from facial nerve paralysis caused by inoculation with HSV-1. The HSV-1 DNA in bilateral facial nerve and bilateral trigeminal ganglion after the treatment were examined with polymerase chain reaction (PCR) analysis. RESULTS There were 10 mice of facial nerve paralysis in the first group. The incidence of facial nerve paralysis was 50% and the duration of facial nerve paralysis was (7.2 +/- 2.2) days. There were 6 mice of facial nerve paralysis in the second group. The incidence of facial nerve paralysis was 30% and the duration of facial nerve paralysis was (4.5 +/- 1.8) days. There were 16 mice of facial nerve paralysis in the control group. The incidence of facial nerve paralysis was 67% and the duration of facial nerve paralysis was (8.9 +/-2.6) days. IgG didn't reduce the incidence and duration of facial nerve paralysis by statistics analysis (P > 0.05), but interferon reduced the incidence and duration of facial nerve paralysis (P < 0.05). After administration of ciclosporin, 3/28 of mice developed facial nerve paralysis. The HSV-1 DNA was detected from facial nerve of all the mice of facial palsy. No facial palsy was observed in mice in which no HSV-1 DNA was detected from facial nerve.

CONCLUSIONSFacial nerve paralysis might be caused by reactivation of latent HSV-1, and the reactivation might be related with immunosuppression. Administration of interferon reduces the incidence and duration of facial nerve paralysis. Administration of IgG can't reduced the incidence and duration of facial nerve paralysis.

Animals ; DNA, Viral ; isolation & purification ; Disease Models, Animal ; Facial Paralysis ; etiology ; prevention & control ; virology ; Female ; Herpes Simplex ; complications ; pathology ; Herpesvirus 1, Human ; pathogenicity ; Immunoglobulin G ; therapeutic use ; Interferons ; therapeutic use ; Mice ; Mice, Inbred BALB C ; Recurrence

OBJECTIVETo study the infection of human cytomegalovirus (HCMV) and herpes simplex virus type II (HSV-I) and the morphological characteristics of the infected spermatogenic cells in the semen of infertile men.

METHODSWe washed and concentrated the spermatogenic cells obtained from 83 semen samples of infertile men, extracted DNA and then screened HCMV and HSV-II by polymerase chain reaction (PCR). Immunocytochemistry (ICC) was used to detect the expression of correlative virus antigens of the positive semen cells, and the cytology smear was employed to observe the morphological changes of the spermatogenic cells under the microscope after cytology staining.

RESULTSOf all the semen samples, 8 were HCMV positive, 4 HSV-II positive, but none were both HCMV and HSV-II positive. HCMV late antigens were positively and HCMV early antigens negatively expressed in the spermatogenic cells of the 8 HCMV positive cases. In the 4 HSV-II positive cases, 3 were positively and 1 weakly positively expressed. In the semen of the 12 positive cases were found large numbers of immature spermatogenic cells, with different manifestations of apoptosis, such as chromatin pycnosis, vacuoles, damaged nuclear membrane, and apoptotic bodies, but without virus infection-induced specific morphological alteration. Sperm concentration of the positive group was significantly lower than that of the negative (P < 0. 05).

CONCLUSIONSpermatogenic cells infected by HCMV and HSV-II may cause pathologic lesions and affect spermatogenesis. Morphologically, the infected spermatogenic cells may undergo some pathologic alteration, such as apoptosis. The rate of HCMV infection is higher among infertile males with pathologic cells in the semen.

Adult ; Antigens, Viral ; analysis ; Cytomegalovirus ; genetics ; immunology ; Cytomegalovirus Infections ; pathology ; virology ; DNA, Viral ; genetics ; Herpes Simplex ; pathology ; virology ; Herpesvirus 2, Human ; genetics ; immunology ; Humans ; Immunohistochemistry ; Infertility, Male ; pathology ; virology ; Male ; Polymerase Chain Reaction ; Semen ; cytology ; virology ; Spermatozoa ; cytology ; virology