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HSV-1
Terms modified by HSV-1 Selected AbstractsMS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus-specific IgG antibodies produced in vivo and by CSF B cells in vitroEUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2009G. Skorstad Background:, Intrathecal synthesis of oligoclonal IgG antibodies against measles virus (MeV), varicella zoster virus (VZV) and herpes simplex virus type-1 (HSV-1) is a characteristic feature multiple sclerosis (MS). Methods:, We have used isoelectric focusing-immunoblot to define the clonal patterns of IgG and of IgG antibodies to MeV, VZV and HSV-1 in supernatants of in vitro cultures of peripheral blood lymphocytes (PBL) and cerebrospinal fluid (CSF) cells and in sera and CSF from three patients with MS and three patients with clinically isolated syndromes (CIS) suspective of demyelinating disease. Results:,In vitro synthesis of IgG by PBL was not detected in any patient. In contrast, in vitro synthesis by CSF cells of oligoclonal IgG and oligoclonal IgG antibodies to one or two of the three viruses tested was observed in all six patients. The clonal patterns of the in vitro synthesized IgG and virus specific IgG differed to varying extent from those synthesized intrathecally in vivo. However, in each patient, the in vitro and in vivo intrathecally produced antibodies displayed specificity for the same viruses. The addition of B cell activating factor (BAFF) had no effect on the amounts or clonal patterns of either total IgG or virus-specific IgG produced by CSF cells in vitro. Conclusion:, Virus specific B cells capable of spontaneous IgG synthesis are clonally expanded in the CSF of patients with MS. The B-cell repertoire in CSF samples is only partially representative of the intrathecal B-cell repertoire. [source] Effect of undernourishment on Herpes Simplex Virus Type 1 ocular infection in the Wistar rat modelINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2002FABIÁN BENENCIA Abstract. ,We have studied the susceptibility to Herpes Simplex Virus Type 1 (HSV-1) infection in malnourished rats. Groups of 10 rats were undernourished during suckling by offspring duplication. The animals were put on commercial diet and at 1, 2, 3, 5 and 8 weeks after weaning, infected in the eye by scarification with HSV-1, strain F. Significant differences in morbidity and mortality were observed between malnourished and control groups infected three weeks after weaning. Viral titres were higher in ocular washings and brains obtained from the malnourished group. This group showed a diminution in antigen dependent lymphocyte proliferation compared to control, and significantly lower delayed type hypersensitivity reaction against inactivated virus (malnourished = 0.16 ± 0.02 mm, control = 0.26 ± 0.03 mm, p < 0.05). Neutralizing antibodies in serum were lower in the malnourished group and lower levels of interferon were obtained in the malnourished group 24 h post-infection. We conclude that malnutrition during suckling induces a delay in the capability to overcome HSV infection. [source] The Role of DNA Recombination in Herpes Simplex Virus DNA ReplicationIUBMB LIFE, Issue 8 2003Dianna Wilkinson Abstract In many organisms the processes of DNA replication and recombination are closely linked. For instance, in bacterial and eukaryotic systems, replication forks can become stalled or damaged, in many cases leading to the formation of double stranded breaks. Replication restart is an essential mechanism in which the recombination and repair machinery can be used to continue replication after such a catastrophic event. DNA viruses of bacteria such as lambda and T4 also rely heavily on DNA recombination to replicate their genomes and both viruses encode specialized gene products which are required for recombination-dependent replication. In this review, we examine the linkage between replication and recombination in the eukaryotic pathogen, Herpes Simplex Virus Type 1 (HSV-1). The evidence that recombination plays an intrinsic role in HSV-1 DNA replication and the infection process will be reviewed. We have recently demonstrated that HSV-1 encodes two proteins which may be analogous to the lambda phage recombination system, Red ,and ,. The HSV-1 alkaline nuclease, a 5' to 3' exonuclease, and ICP8, a single stranded DNA binding protein, can carry out strand annealing reactions similar to those carried out by the lambda Red system. In addition, evidence suggesting that host recombination proteins may also be important for HSV-1 replication will be reviewed. In summary, it is likely that HSV-1 infection will require both viral and cellular proteins which participate in various pathways of recombination and that recombination-dependent replication is essential for the efficient replication of viral genomes. IUBMB Life, 55: 451-458, 2003 [source] Herpes viruses in periodontal compromised sites: comparison between HIV-positive and -negative patientsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2008Sabrina Rosa Grande Abstract Aim: The objective of this study was to compare the frequency of herpes simplex virus type 1 (HSV-1), Epstein,Barr virus (EBV) and human cytomegalovirus (HCMV) in subgingival plaque, saliva and peripheral blood of HIV-positive and-negative patients with periodontal disease. Material and Methods: Fifty HIV-positive subjects (23 with gingivitis, 27 with periodontitis) and 50 healthy HIV-negative patients with chronic periodontitis were included in the study. Parameters of probing depth (PD), clinical attachment level (CAL), gingival index and plaque index were recorded. The samples were processed for viral identification by the nested polymerase chain reaction technique. Results: HCMV was the most prevalent virus in HIV-positive (82%) and-negative patients (84%), and the detection in the three samples was similar (p>0.05). HSV-1 was the least prevalent virus in both groups, being detected in similar frequencies in oral sites and in peripheral blood. EBV-1 was found more frequently in saliva and subgingival plaque of HIV-positive patients than in HIV-negative patients (p0.05). Conclusions: EBV-1 was more frequently recovered in oral sites of HIV-positive patients than in HIV-negative patients. [source] In vitro effect of oral antiseptics on human immunodeficiency virus-1 and herpes simplex virus type 1JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 7 2001A. A. M. A. Baqui Abstract Aim: The antiviral effectiveness of widely used commercial mouthrinses has not been well studied. A project was undertaken to evaluate and compare the in vitro antiviral effectiveness of essential oil-containing mouthrinses (LA & TLA) and chlorhexidine mouthrinses (PX & CHX) on 2 different enveloped viruses, human immunodeficiency virus (HIV-1) and Herpes simplex virus (HSV-1) McIntyre strain. Method: HIV-189.6 (1×105/ml) and HSV-1 (1×106/ml) in RPMI-1640 medium were treated with two commercially available forms of LA & TLA (tartar control LA), and 2 formulations of chlorhexidine [(PX), 0.12% chlorhexidine & (CHX), 0.2% chlorhexidine] for 30 sec. The antiviral effect was estimated by inhibition of the syncytia formation or the cytopathic effect (CPE) for HIV-1 on MT-2 cells and by inhibition of the plaque formation for HSV-1 on Vero cell monolayers. Results: Undiluted LA, TLA, PX and CHX completely inhibited both HIV-189.6 and HSV-1 McIntyre strain. PX and CHX inhibited HIV-1 up to 1:4 dilution, whereas, LA and TLA inhibited HSV-1 up to 1:2 dilution. The antiviral effects of LA and TLA were found to be similar and also the antiviral effect of PX and CHX were also found to be comparable. Conclusions: The methods used in this investigation allow easy and reproducible evaluations of antiviral efficacy. The anti-HIV-1 and anti-HSV-1 effects of LA, TLA, PX and CHX as evidenced in our in vitro study suggest that we should investigate potential in vivo effects during the use of essential oil-containing or chlorhexidine containing products when used by patients as mouthrinses. If the clinical studies confirm the in vitro data, pre-procedural use by clinicians may be beneficial in reducing viral contamination of bio-aerosols during the delivery of dental care. Zusammenfassung Ziel: Die antivirale Effektivität von breit genutzten kommerziellen Mundwässern wurde bisher nicht gut untersucht. Ein Projekt wurde deshalb aufgenommen, um den in vitro antiviralen Effekt von ätherischen Öl enthaltenden Mundwässern (LA & TLA) und Chlorhexidin Mundwässern (PX & CHX) auf 2 unterschiedlich entwickelte Viren, das menschliche Immundefizienz Virus (HIV-1) und das Herpes simplex Virus (HSV-1) McIntyre Stamm zu evaluieren und zu vergleichen. Methoden: HIV-189.6 (1×105/ml) und HSV-1 (1×106/ml) in RPMI-1640 Medium wurden mit 2 kommerziellen Formen von LA & TLA (Tartarkontrolle LA) und 2 Arten von Chlorhexidin [(PX), 0.12% Chlorhexidin & (CHX), 0.2% Chlorhexidin] für 30 Sekunden behandelt. Der antivirale Effekt wurde durch Inhibition der Syncytiumbildung oder des cytopathischen Effektes (CPE) für HIV-1 auf MT-2 Zellen und durch Inhibition der Plaquebildung für HSV-1 auf Vero Zellmonolayers bestimmt. Ergebnisse: Unverdünntes LA, TLA, PX und CHX inhibierte sowohl HIV-189.6 und HSV-1 McIntyre Stamm. PX und CHX inhibierte HIV-1 bis zu einer 1:4 Verdünnung, während LA und TLA HSV-1 bis zu einer 1:2 Verdünnung inhibierte. Die antiviralen Effekte von LA und TLA wurden gleichwertig gefunden und auch der antivirale Effekt von PX und CHX waren vergleichbar. Zusammenfassung: Die genutzten Methoden in dieser Untersuchung erlaubten leicht und reproduzierbar die Evaluation von antiviralen Effekten. Die anti-HIV-1 und anti-HSV-1 Effekte von LA, TLA, PX und CHX, die in unserer in vitro Studie evident waren, suggerieren, daß wir das Potential der in vivo Effekte während des Gebrauches von ätherischen Öl enthaltenden oder Chlorhexidin enthaltenden Produkten untersuchen sollten, wenn die Patienten dies als Mundwässer benutzen. Wenn die klinischen Studien die in vitro Ergebnisse bestätigen, kann der vorherige Gebrauch durch die Kliniker die virale Kontamination von Bioaerosolen während der durchgeführten zahnäztlichen Behandlung reduzieren. Résumé But: L'efficacité antivirale des bains de bouches largement commercialises n'a pas été bien étudiée. Notre projet a évalué et comparé l'efficité antivirale in vitro de bains de bouche aux huiles essentielles (LA et TLA) et à la chlorexhidine (PX et CHX) sur 2 virus à envelopes, le virus de l'immunodéfiscience acquise 1 (HIV1) et la souche McIntyre du virus de l'Herpes simplex de type 1 (HSV1). Méthode: HIV1896 (1×105/ml) et HSV1 (1×106 ml) dans un milieu RPMI-1640 furent traits avec 2 formes disponibles sur le marché de LA et TLA, et 2 formules de chloxhexidine (PX, 0.12% chlorexhidine et CHX, 0.2% chlorexhidine) pendant 30 s. L'effet antiviral fut estimé par l'inhibition de la formation de syncitia ou par l'effet cytopathique (CPE) pour HIV1, sur des cellules MT2 et par l'inhibition de la formation de plaque pour HSV1 sur des monocouches cellulaires Vero. Résultats: CHX, LA, TLA et PX non dilués inhibaient complètement à la fois HIV1896 et la souche McIntyre HSV1. PX et CHX inhibaient HIV1 jusqu'à une dilution par 4 alors que LA et TLA inhibaient HSV1 jusqu'à une dilution par 2. Les effets antiviraux de LA et TLA étaient similaires, et les effets antiviraux de PX et CHX étaient aussi comparables. Conclusions: Les methodes utilisées pour cette recherche permettent une évaluation facile et reproductible de l'efficacité antivirale. Les effets anti-HIV1 et anti-HSV1 de LA, TLA, PX et CHX trouvés ici in vitro suggèrent que nous recherchions des effects potentiels in vivo lors de l'utilisation de produits contenant des huiles essentielles ou de la chlorexhidine utilisés comme bains de bouches par les patients. Si les études cliniques confirment les données in vitro, l'utilisation préclinique par les praticiens pourrait leur être bénéfique en réduisant la contamination virale des bioaérosols lors des soins dentaires. [source] Synthesis of acyclic nucleoside phosphonates as antiviral compoundsJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2000Frank Wormstädt Reaction of 6-chloropyrimidines with diethyl [(2-aminoethoxy)methyl]phosphonate allows for a ready access to acyclic nucleoside phosphonates. A series of 5-substituted pyrimidines bearing a phosphonate side chain at position 6 were synthesized and tested against herpes simplex viruses (HSV-1 and HSV-2) and human immunodeficiency virus (HIV-1). Some compounds showed weak antiviral activity against HSV-1. [source] Naturally occurring fatal herpes simplex virus 1 infection in a family of white-faced saki monkeys (Pithecia pithecia pithecia)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2003M.D. Schrenzel Abstract: A family of three white-faced saki monkeys (Pithecia pithecia pithecia) died 48,96 hours after the onset of anorexia, nasal discharge, pyrexia and oral ulceration. One animal also had clonic seizures. Lesions found post-mortem consisted of oral and esophageal ulcers, hepatic and intestinal necrosis, meningoencephalitis and sporadic neuronal necrosis. Intranuclear inclusion bodies and syncytial cells were present in oral lesions and affected areas of liver. Herpes simplex virus 1 (HSV-1) was identified as the etiology of disease by virus isolation, polymerase chain reaction, or in situ hybridization in all three animals. Immunohistochemistry for detection of apoptotic DNA and activated caspase-3 showed significant levels of apoptosis in oral and liver lesions and occasional apoptotic neurons in the brain. These findings demonstrate the vulnerability of white-faced saki monkeys to HSV-1 and provide initial insight into the pathogenesis of fatal HSV-1-induced disease, indicating that apoptosis plays a significant role in cell death. [source] Serological evidence of alpha herpesvirus infection in sooty mangabeysJOURNAL OF MEDICAL PRIMATOLOGY, Issue 3 2002R.D. Henkel Contact between sooty mangabeys (SMs) and a pigtailed macaque prompted the serological screening of SMs for evidence of infection with B virus. Serological tests detected SM antibodies that reacted with B virus polypeptides. Additional testing was performed with sera from SMs with no previous contact with macaques. Results from these tests indicated that 56% (33/59) of the SMs had antibodies that reacted with B virus and SA8. SM antibodies also reacted with herpesvirus papio 2 and to a lesser extent with human alpha herpesviruses (HSV-1 and HSV-2). There was an age-related increase in the presence of these antibodies in SMs that was consistent with the serological pattern of reactivity observed in other nonhuman primate species infected with alpha herpesviruses. These data suggest that SMs may be a host for a herpesvirus that is antigenically similar to those viruses present in other Old World nonhuman primates. [source] Viral loads of herpes simplex virus in clinical samples,A 5-year retrospective analysis,JOURNAL OF MEDICAL VIROLOGY, Issue 11 2010Julian W. Tang Abstract Viral loads of herpes simplex virus (HSV) are not monitored usually for the effective clinical management of HSV-related diseases. However, recently, there has been more interest about the typical HSV levels in clinical specimens, and how such data may improve understanding of the behavior of this virus in such clinical presentations, particularly in immunocompromised patients, where more prolonged therapy using higher doses of antiviral drugs may be required. Using an in-house quantitative HSV-1/HSV-2 polymerase chain reaction assay, an observational, retrospective 5-year analysis of diagnostic, quantitative HSV-1 and HSV-2 DNA levels was conducted. The results (all in median log10 DNA copies/ml), including perhaps the first quantitative comparison of cerebrospinal fluid (CSF) HSV viral loads, were as follows: CSF: HSV-1, 3.40 (range 2.30,8.98) versus HSV-2, 3.60 (range 2.31,6.86) (P,=,0.559); plasma: HSV-1, 3.20 (range 2.23,5.51) versus HSV-2, 3.20 (range 3.18,3.41) (P,=,0.905); genital swabs: HSV-1, 6.79 (range 2.28,8.48) versus HSV-2, 6.97 (range 3.40,9.66) (P,=,0.810); oral swabs: HSV-1, 7.28 (range 2.46,10.04) versus HSV-2, 5.62 (range 4.60,6.63) (P,=,0.529). Note that with the samples usually collected for HSV testing (i.e., CSF, plasma, oral, and genital swabs) there was no significant difference in the viral loads between HSV-1 and HSV-2 types, nor between immunocompetent and immunocompromised patients for each of these different HSV types. Indeed, even between immunocompromised patients with similar diseases, for these samples, the HSV loads were found to vary considerably. These findings may therefore limit the usefulness of monitoring HSV loads in everyday clinical practice. J. Med. Virol. 82:1911,1916, 2010. © 2010 Wiley-Liss, Inc. [source] Early and reliable detection of herpes simplex virus type 1 and varicella zoster virus DNAs in oral fluid of patients with idiopathic peripheral facial nerve palsy: Decision support regarding antiviral treatment?JOURNAL OF MEDICAL VIROLOGY, Issue 9 2010Andreas Lackner Abstract Idiopathic peripheral facial nerve palsy has been associated with the reactivation of herpes simplex virus type 1 (HSV-1) or varicella zoster virus (VZV). In recent studies, detection rates were found to vary strongly which may be caused by the use of different oral fluid collection devices in combination with molecular assays lacking standardization. In this single-center pilot study, liquid phase-based and absorption-based oral fluid collection was compared. Samples were collected with both systems from 10 patients with acute idiopathic peripheral facial nerve palsy, 10 with herpes labialis or with Ramsay Hunt syndrome, and 10 healthy controls. Commercially available IVD/CE-labeled molecular assays based on fully automated DNA extraction and real-time PCR were employed. With the liquid phase-based oral fluid collection system, three patients with idiopathic peripheral facial nerve palsy tested positive for HSV-1 DNA and another two tested positive for VZV DNA. All patients with herpes labialis tested positive for HSV-1 DNA and all patients with Ramsay Hunt syndrome tested positive for VZV DNA. With the absorption-based oral fluid collection system, detections rates and viral loads were found to be significantly lower when compared to those obtained with the liquid phase-based collection system. Collection of oral fluid with a liquid phase-based system and the use of automated and standardized molecular methods allow early and reliable detection of HSV-1 and VZV DNAs in patients with acute idiopathic peripheral facial nerve palsy and may provide a valuable decision support regarding start of antiviral treatment at the first clinical visit. J. Med. Virol. 82:1582,1585, 2010. © 2010 Wiley-Liss, Inc. [source] Serologic and genotypic analysis of a series of herpes simplex virus type 1 isolates from two patients with genital herpesJOURNAL OF MEDICAL VIROLOGY, Issue 9 2009Kenichi Umene Abstract Herpes simplex virus type 1 (HSV-1) has been reported increasingly as a cause of genital herpes, although HSV-1 is usually associated with oro-labial herpes. In the present study, serum specimens and materials for viral isolation were obtained serially from two patients with recrudescent HSV-1 genital infections to study serology and molecular epidemiology. Recurrent episodes, during which HSV-1 was isolated, were followed by an increase in the level of anti-HSV-1 antibody, suggesting a booster effect from re-exposure to viral antigens and the possible usefulness of the variation in the level of anti-HSV-1 antibody to diagnose recurrence. While genotypes of HSV-1 isolates obtained from one patient were different from those from the other patient, genotypes of sequential HSV-1 isolates obtained from the same patient were the same, implying that the recrudescent genital lesions of the two patients could be attributed to endogenous recurrence of a latent virus. Sera from one patient neutralized HSV-1 isolates obtained from the other patient as well as HSV-1 isolates obtained from the same patient. An HSV-1 isolate obtained during a later episode in one patient was neutralized by sera taken before/during the later episode of the same patient, as effectively as an HSV-1 isolate obtained during an earlier episode in the same patient; thus, in these two cases, HSV-1 was assumed to have multiplied during recurrence despite the presence of an anti-HSV-1 antibody that could neutralize experimentally HSV-1. J. Med. Virol. 81:1605,1612, 2009. © 2009 Wiley-Liss, Inc. [source] Prevalence of human papilloma virus and human herpes virus types 1,7 in human nasal polyposisJOURNAL OF MEDICAL VIROLOGY, Issue 9 2009Apostolos Zaravinos Abstract This study aimed to investigate the prevalence of human papilloma virus (HPV), herpes simplex virus-1/-2 (HSV-1/-2), varicella-zoster virus (VZV), Epstein,Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6/-7 (HHV-6/-7) in 23 human nasal polyps by applying PCR. Two types of control tissues were used: adjacent inferior/middle turbinates from the patients and inferior/middle turbinates from 13 patients undergoing nasal corrective surgery. EBV was the virus most frequently detected (35%), followed by HPV (13%), HSV-1 (9%), and CMV (4%). The CMV-positive polyp was simultaneously positive for HSV-1. HPV was also detected in the adjacent turbinates (4%) and the adjacent middle turbinate (4%) of one of the HPV-positive patients. EBV, HSV, and CMV were not detected in the adjacent turbinates of the EBV-, HSV- or CMV-positive patients. All mucosae were negative for the VZV, HHV-6, and HHV-7. This is the first study to deal with the involvement of a comparable group of viruses in human nasal polyposis. The findings support the theory that the presence of viral EBV markedly influences the pathogenesis of these benign nasal tumors. The low incidence of HPV detected confirms the hypothesis that HPV is correlated with infectious mucosal lesions to a lesser extent than it is with proliferative lesions, such as inverted papilloma. The low incidence of HSV-1 and CMV confirms that these two herpes viruses may play a minor role in the development of nasal polyposis. Double infection with HSV-1 and CMV may also play a minor, though causative, role in nasal polyp development. VZV and HHV-6/-7 do not appear to be involved in the pathogenesis of these mucosal lesions. J. Med. Virol. 81:1613,1619, 2009. © 2009 Wiley-Liss, Inc. [source] Oral mucosal reactivation rates of herpesviruses among HIV-1 seropositive personsJOURNAL OF MEDICAL VIROLOGY, Issue 7 2008Elizabeth Griffin Abstract Herpes simplex virus, cytomegalovirus and Epstein-Barr virus infections are prevalent among HIV-1 infected persons. The relationships between salivary shedding of these herpesviruses have not been characterized. Salivary samples were collected on a median of 61 consecutive days from 41 HIV-1 seropositive persons and tested for HSV-1, HSV-2, CMV and EBV. HSV was detected on 5%, CMV on 19% and EBV on 71% of the days of sampling. HSV shedding was not related to CMV or EBV shedding rates. Persons with EBV shedding rates >40% had CMV DNA detected in their saliva significantly more often than those with EBV shedding rates ,40% (P,=,0.008). The odds of detecting CMV were greater on days with HSV (OR 2.5, 95% CI 1.4, 4.4) or EBV (OR 3.8, 95% CI 1.9, 7.9) shedding. No significant associations between HSV shedding rates and CD4 count, plasma HIV-1 RNA or HAART were observed. Increasing plasma HIV-1 RNA was associated with greater frequency (P,=,0.01) and quantity (P,<,0.001) of EBV shedding. Among persons not receiving HAART, CD4 counts >200 cells/mm3 were associated with lower frequency (P,=,0.02) and quantity (P,=,0.03) of CMV compared with CD4 counts ,200 cells/mm3. These data suggest that separate factors influence mucosal shedding of each of the three classes of herpesviruses but that virological interactions between the pathogens also exist. J. Med. Virol. 80: 1153,1159, 2008. © 2008 Wiley-Liss, Inc. [source] Association of viral factors with non-familial breast cancer in Taiwan by comparison with non-cancerous, fibroadenoma, and thyroid tumor tissues,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2005Ju-Hsin Tsai Abstract To study the etiologic factors of non-familial breast cancer, the polymerase chain reaction (PCR) and Southern hybridization were used to detect six viruses including human papillomavirus (HPV), cytomegalovirus (CMV), Epstein,Barr virus (EBV), herpes simplex virus (HSV)-1, HSV-2, and human herpesvirus (HHV)-8 DNA in 69 patients with breast cancer and 60 specimens from non-cancerous or other individuals with thyroid tumors or fibroadenoma (non-breast cancer controls). Two specimens from patients with a familial history of breast cancer and five breast cancer specimens with negative results for ,-globin, which was used as internal control, were excluded from this study. Eight (12.9%) HSV-1, 28 (45.2%) EBV, 47 (75.8%) CMV, 8 (12.9%) HPV, and 28 (45.2%) HHV-8 positive samples out of the 62 breast cancer specimens were detected; no HSV-2 DNA was detected in any group. Among the viral gene-positive breast cancer samples, 12 (23.1%) were positive for 1 virus, 16 (30.8%) were positive for 2 viruses, 21 (40.4%) were positive for 3 viruses, and 3 (5.8%) were positive for 4 viruses. Among the viral gene-positive specimens of the control groups, only one virus, CMV, was found in the non-cancerous and thyroid tumor specimens, while multiple viruses were found in the fibroadenoma specimens. The viruses associated with breast cancer were HHV-8,>,EBV (P,<,0.01). The viruses associated with fibroadenoma were HSV-1 and HHV-8,>,EBV (P,<,0.01). The presence of more than one virus was found predominantly in breast cancer and exclusively found in fibroadenoma. CMV was the only virus associated with thyroid tumors. J. Med. Virol. 75:276,281, 2005. © 2004 Wiley-Liss, Inc. [source] Hexokinase II gene transfer protects against neurodegeneration in the rotenone and MPTP mouse models of Parkinson's disease,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010Juan Carlos Corona Abstract A typical feature of Parkinson's disease is the progressive loss of dopaminergic neurons in the substantia nigra, in which inhibition of mitochondrial complex I activity may play an important role. Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibit the mitochondrial complex I and they cause the death of substantia nigra dopaminergic neurons, thereby providing acute murine models of Parkinson's disease. We have found that increasing mitochondrial hexokinase II activity can prevent cell death in neuronal cultures treated with rotenone. As a result, we have studied the effects of hexokinase II gene transfer in vivo using a herpes simplex virus type 1 (HSV-1) amplicon vector. The placHK2 amplicon vector was injected into substantia nigra of mice that were subsequently administered rotenone or MPTP. Overexpression of hexokinase II prevented both rotenone and MPTP-induced dopaminergic neuronal cell death, as well as reducing the associated motor defects. Our results provide the first proof-of-principle that hexokinase II protects against dopaminergic neurodegeneration in vivo, emphasizing the role of this enzyme in promoting neuronal survival. Thus, the increase of hexokinase II expression by gene transfer or other means represents a promising approach to treat Parkinson's and other neurodegenerative diseases. © 2010 Wiley-Liss, Inc. [source] Mass spectrometric and chemical stability of the Asp-Pro bond in herpes simplex virus epitope peptides compared with X-Pro bonds of related sequencesJOURNAL OF PEPTIDE SCIENCE, Issue 8 2002Zsolt Skribanek Abstract The mass spectrometric analysis of the immunodominant epitope region (273,284) of herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) showed a favoured fission at the Asp-Pro peptide bond. The fast atom bombardment collision induced dissociation (FAB-CID) study of closely related X-Pro peptides documented that neither the length nor the amino acid composition of the peptide has a significant influence on this preferential cleavage. At the same time the DP bond proved to be sensitive to acidic conditions in the course of peptide synthesis. These observations prompted us to compare the chemical and mass spectrometric stability of a new set of nonapeptides related to the 273,284 epitope region of gD, i.e. SALLEDPVG and SALLEXPVG peptides, where X = A, K, I, S, F, E or D, respectively. The chemical stability of these peptides during acidic hydrolysis was investigated by electrospray ionization mass spectrometry (ESI-MS) and the products were identified by ESI-MS and on-line high performance liquid chromatography,mass spectrometry (HPLC-MS). The mass spectrometric fragmentation and bond stability of the untreated peptide samples were also studied using ESI-MS and liquid secondary ion mass spectrometry (LSIMS). Both the chemical hydrolysis and the mass spectrometric fragmentation showed that the Asp-Pro bond could easily be cleaved, while the KP bond proved to be stable under both circumstances. On the other hand, the XP bond (X = A, I, S, F or E) fragmented easily under the mass spectrometric conditions, but was not sensitive to the acidolysis. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Antibacterial, antiviral, antiproliferative and apoptosis-inducing properties of Brackenridgea zanguebarica (Ochnaceae)JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2006Maren Möller Brackenridgea zanguebarica is a small tree that is used in traditional African medicine as a type of cure-all for many diseases, including the treatment of wounds. The yellow bark of B. zanguebarica was used for the preparation of an ethanolic extract, which was tested in various concentrations against eleven bacteria, Herpes simplex virus type 1 (HSV-1) and different human tumour cell lines. The extract that contains different polyphenolic substances like calodenin B. Cell growth inhibition, assessed via MTT-assay, was found in all tested human cell lines with IC50 values (concentration of extract that reduced cell viability by 50%) between 33 ,g dry extract/mL for HL-60 human myeloid leukaemia cells and 93 ,g dry extract/mL for HaCaT human keratinocytes. Staining with Annexin-V-FLUOS and JC-1 followed by subsequent analysis via flow cytometry revealed significant apoptosis-inducing properties. Analysis of caspase activity using a fluorogenic caspase-3 substrate showed a significant caspase activity in Jurkat T-cells after incubation with the extract. The bark extract had a pronounced activity against free HSV-1 and a strong antibacterial activity against Gram-positive strains (MICs: 6,24 ,g dry extract/mL), which are often involved in skin infections. Additionally, no irritating properties of the extract could be observed in hen-egg test chorioallantoic membrane (HET-CAM) assay. These findings give a rationale for the traditional use of B. zanguebarica and are a basis for further analysis of the plant's components, their biological activity, and its use in modern phytotherapy. [source] Herpes simplex virus type 1 dysregulates anti-fungal defenses preventing monocyte activation and downregulating toll-like receptor-2MICROBIOLOGY AND IMMUNOLOGY, Issue 12 2008Claudio Cermelli ABSTRACT We investigated the interplay occurring between pathogens in the course of dual infections, using an in vitro model in which the THP-1 monocytic cell line is first infected with HSV-1 and then exposed to Ca or Cn. These three pathogens share some pathogenic features: they cause opportunistic infections, target macrophages and are neurotropic. Here, we show that HSV-1-infected THP-1 cells exhibited augmented phagocytosis against the two opportunistic fungi but reduced capability to counteract fungal infection: the better ingestion by monocytes was followed by facilitated fungal survival and replication. Reduced IL-12 production was also observed. Cytofluorimetric analysis showed that HSV-1-infected monocytes exhibit: (i) downregulated TLR-2 and TLR-4, critical structures in fungal recognition; (ii) reduced expression of CD38 and CD69, known to be important markers of monocyte activation; and (iii) enhanced expression of apoptosis and necrosis markers, in the absence of altered cell proliferation. Overall, these findings imply that HSV-1 infection prevents monocyte activation, thus leading to a significant dysfunction of the monocyte-mediated anti- Candida response; HSV-1 induced apoptosis and necrosis of monocytes further contribute to this impairment. [source] Subclinical reactivation of herpes simplex virus type 1 in the oral cavityMOLECULAR ORAL MICROBIOLOGY, Issue 5 2000B. Knaup Reactivation in the oral cavity either symptomatically (recrudescence) or without symptoms (recurrence) may contribute to the transmission of herpes simplex virus type 1 (HSV-1), especially in critical areas of exposure such as dentistry. In order to measure the frequency of HSV-1 reactivation, nested polymerase chain reaction (PCR) was performed on oral swabs collected from 30 healthy people over a period of 58,161 days. In total 19 of 25 (76%) seropositive people were PCR-positive at least once, 6 of these 19 (32%) had recrudescence and 13 (68%) had only asymptomatic reactivation. Frequencies of additional recurrences were higher in people showing symptomatic reactivation than in those who had only recurrences. Recrudescence is a risk factor for elevated levels of asymptomatic HSV-shedding. In most cases HSV-1 was detected only by nested PCR investigated by early onset of therapy or time span before sampling. [source] Using community pharmacies to conduct an HSV-1 prevalence studyPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2002Joseph C. Veltri PharmD Abstract Purpose To describe the effectiveness of community-based pharmacists in conducting a study to measure the baseline prevalence of Herpes simplex virus, type-1 susceptibility to two antiviral medications in subjects with recurrent Herpes labialis Method A cross-sectional study conducted in 47 US community pharmacies. The pharmacist obtained a viral sample from the surface of the lesion, placed the virus-laden swab in a vial of holding medium, and stored it in a refrigerator until shipment to a central laboratory. Results The population that had swabs processed for viral isolation (1795) was predominantly white (90.1%) and female (67.9%) with a mean age of 37.5 years. A total of 1087 (60.3%) swabs were positive for HSV-1. On-site monitoring revealed 219 protocol deviations related to the stage of the lesion (124), not properly dating or signing the consent form (80), and indeterminate age (15). Conclusions This study demonstrates the ability of pharmacists to conduct a large surveillance study in busy community pharmacies. A population of RHL sufferers with active lesions was recruited to study pharmacies during a 5-month period. Pharmacists successfully obtained viral samples from cold sore lesions at a rate comparable to physician-conducted studies. Protocol deviations were generally not serious, and did not compromise the study results or endanger the rights or welfare of participants. Copyright © 2002 John Wiley & Sons, Ltd. [source] Antiviral triterpenoids from the medicinal plant Schefflera heptaphyllaPHYTOTHERAPY RESEARCH, Issue 5 2007Yaolan Li Abstract Schefflera heptaphylla (L.) Frodin is a principal ingredient of an herbal tea formulation widely used for the treatment of common cold in southern China. An extract of the long leafstalk of the compound leaf of S. heptaphylla exhibited the most potent antiviral activity against respiratory syncytial virus (RSV). Further antiviral-guided fractionation and isolation of the leafstalk extract of S. heptaphylla led to obtain two highly active pure triterpenoids, namely 3, -hydroxylup-20(29)-ene-23,28-dioic acid and 3- epi -betulinic acid 3- O -sulfate, together with an inactive saponin, 3, -hydroxylup-20(29)-ene-23,28-dioic acid 28- O - , - l -rhamnopyranosyl-(1,4)- O - , - d -glucopyranosyl-(1,6)- , - d -glucopyranoside. An antiviral assay using a cytopathic effect (CPE) reduction method showed that the two triterpenoids possessed broader antiviral activity against respiratory syncytial virus (RSV) with a similar 50% inhibition concentration (IC50) value of 6.25 µg/mL, influenza A (H1N1) virus with IC50 values of 25 and 31.3 µg/mL, Coxsackie B3 (Cox B3) virus with IC50 values of 12.5 and 20 µg/mL and herpes simplex virus type 1 (HSV-1) with IC50 values of 18.8 and 25 µg/mL, respectively, whereas the saponin did not have antiviral activity against these four viruses at a concentration of 100 µg/mL. Copyright © 2007 John Wiley & Sons, Ltd. [source] Virucidal activity of essential oils from aromatic plants of San Luis, ArgentinaPHYTOTHERAPY RESEARCH, Issue 9 2003C. C. García Abstract Essential oils obtained from eight aromatic plants of San Luis Province, Argentina, were screened for virucidal activity against herpes simplex virus type 1 (HSV-1), Junin virus (JUNV) and dengue virus type 2 (DEN-2). The most potent inhibition was observed with the essential oil of Lippia junelliana and Lippia turbinata against JUNV with virucidal concentration 50% (VC50) values in the range 14,20 ppm, whereas Aloysia gratissima, Heterotheca latifolia and Tessaria absinthioides inhibited JUNV in the range 52,90 ppm. The virucidal activity was time- and temperature-dependent. The essential oils of A. gratissima, Artemisia douglasiana, Eupatorium patens and T. absinthioides inactivated HSV-1 at 65,125 ppm. However, only A. douglasiana and E. patens had any discernible effect on DEN-2 infectivity with VC50 values of 60 and 150 ppm, respectively. Copyright © 2003 John Wiley & Sons, Ltd. [source] Characterization of Herpes Simplex Virus type 1 thymidine kinase mutants engineered for improved ganciclovir or acyclovir activityPROTEIN SCIENCE, Issue 9 2002Mark S. Kokoris Abstract Herpes Simplex Virus type 1 (HSV-1) thymidine kinase (TK) is currently the most widely used suicide agent for gene therapy of cancer. Tumor cells that express HSV-1 thymidine kinase are rendered sensitive to prodrugs due to preferential phosphorylation by this enzyme. Although ganciclovir (GCV) is the prodrug of choice for use with TK, this approach is limited in part by the toxicity of this prodrug. From a random mutagenesis library, seven thymidine kinase variants containing multiple amino acid substitutions were identified on the basis of activity towards ganciclovir and acyclovir based on negative selection in Escherichia coli. Using a novel affinity chromatography column, three mutant enzymes and the wild-type TK were purified to homogeneity and their kinetic parameters for thymidine, ganciclovir, and acyclovir determined. With ganciclovir as the substrate, one mutant (mutant SR39) demonstrated a 14-fold decrease in Km compared to the wild-type enzyme. The most dramatic change is displayed by mutant SR26, with a 124-fold decrease in Km with acyclovir as the substrate. Such new "prodrug kinases" could provide benefit to ablative gene therapy by now making it feasible to use the relatively nontoxic acyclovir at nanomolar concentrations or ganciclovir at lower, less immunosuppressive doses. [source] Proteomic analysis of cells in the early stages of herpes simplex virus type-1 infection reveals widespread changes in the host cell proteomePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 15 2009Robin Antrobus Abstract During infection by herpes simplex virus type-1 (HSV-1) the host cell undergoes widespread changes in gene expression and morphology in response to viral replication and release. However, relatively little is known about the specific proteome changes that occur during the early stages of HSV-1 replication prior to the global damaging effects of virion maturation and egress. To investigate pathways that may be activated or utilised during the early stages of HSV-1 replication, 2-DE and LC-MS/MS were used to identify cellular proteome changes at 6,h post infection. Comparative analysis of multiple gels representing whole cell extracts from mock- and HSV-1-infected HEp-2 cells revealed a total of 103 protein spot changes. Of these, 63 were up-regulated and 40 down-regulated in response to infection. Changes in selected candidate proteins were verified by Western blot analysis and their respective cellular localisations analysed by confocal microscopy. We have identified differential regulation and modification of proteins with key roles in diverse cellular pathways, including DNA replication, chromatin remodelling, mRNA stability and the ER stress response. This work represents the first global comparative analysis of HSV-1 infected cells and provides an important insight into host cell proteome changes during the early stages of HSV-1 infection. [source] Poor intercellular transport and absence of enhanced antiproliferative activity after non-viral gene transfer of VP22-P53 or P53-VP22 fusions into p53 null cell lines in vitro or in vivoTHE JOURNAL OF GENE MEDICINE, Issue 7 2005David Zavaglia Abstract Background The herpes simplex virus type 1 (HSV-1) VP22 protein has the property to mediate intercellular trafficking of heterologous proteins fused to its C- or N-terminus. We have previously shown improved delivery and enhanced therapeutic effect in vitro and in vivo with a P27-VP22 fusion protein. In this report, we were interested in studying the spread and biological activity of VP22 fused to the P53 tumor suppressor. Methods Expression of the VP22-P53 and P53-VP22 fusion proteins was shown by Western blot and intercellular spreading was monitored by immunofluorescence on transiently transfected cells. In vitro antiproliferative activity of wild-type (wt) P53 and P53-VP22 was assessed by proliferation assays and transactivating ability was studied by a reporter gene test and a gel-shift assay. Antitumor activity was also tested in vivo by intratumoral injections of naked DNA in a model of subcutaneous tumors implanted in nude mice. Results Our results show that the C-terminal fusion or the N-terminal P53-VP22 fusion proteins are not able to spread as efficiently as VP22. Moreover, we demonstrate that VP22-P53 does not possess any transactivating ability. P53-VP22 has an antiproliferative activity, but this activity is not superior to the one of P53 alone, in vitro or in vivo. Conclusions Our study indicates that a gene transfer strategy using VP22 cannot be considered as a universal system to improve the delivery of any protein. Copyright © 2005 John Wiley & Sons, Ltd. [source] Imaging-guided convection-enhanced delivery and gene therapy of glioblastomaANNALS OF NEUROLOGY, Issue 4 2003Juergen Voges MD In a prospective phase I/II clinical study, we treated eight patients suffering from recurrent glioblastoma multiform with stereotactically guided intratumoral convection-enhanced delivery of an HSV-1- tk gene,bearing liposomal vector and systemic ganciclovir. Noninvasive identification of target tissue together with assessment of vector-distribution volume and the effects of gene therapy were achieved using magnetic resonance imaging and positron emission tomography. The treatment was tolerated well without major side effects. In two of eight patients, we observed a greater than 50% reduction of tumor volume and in six of eight patients focal treatment effects. Intracerebral infusion of contrast medium before vector application displayed substantial inhomogeneity of tissue staining indicating the need of test infusions to monitor the mechanical distribution of vectors. Visualization of therapeutic effects on tumor metabolism and documentation of gene expression using positron emission tomography indicated that molecular imaging technology appears to be essential for the further development of biological treatment strategies. [source] Prevalence of Chlamydophila pneumoniae is higher in aorta and coronary artery than in carotid artery of coronary artery disease patientsAPMIS, Issue 12 2009HEM C. JHA Coronary artery disease (CAD) is a public health problem accounting for an estimated one-third of deaths overall. A potential link between infectious agents and atherosclerosis has been suggested. Data obtained from several seroepidemiological studies have suggested that infection with Chlamydiophila pneumoniae, Helicobacter pylori, cytomegalovirus and herpes simplex virus-1 can initiate or maintain the atherosclerotic process. However, there is no single study in which multiple infectious agents have been detected together in different vascular locations in the same population. This would help in determining if there is any leading pathogen in atheromatous plaques of CAD patients. Hence, we screened for C. pneumoniae, H. pylori, CMV and HSV-1 in different vascular locations of CAD patients using quantitative real-time (RT) PCR. We performed multiplex RT-PCR for detecting pathogens, viz. C. pneumoniae, H. pylori, CMV and HSV-1 in different vascular locations of CAD patients. Percent positivity scores for C. pneumoniae, H. pylori, CMV and HSV-1 in different vascular locations were as follows: aorta (64.7, 35.3, 11.7 and 11.7 respectively); carotid (27.2, 27.2, 9 and 0 respectively); coronary artery (58.3, 33.3, 16.6 and 8.3 respectively). Combined positivity for C. pneumoniae (C. pneumoniae IgA and RT-PCR for C. pneumoniae) was the highest compared with all other groups. Aorta and coronary artery were more susceptible to these pathogens as compared with carotid artery. Moreover, CAD patients' characteristics were associated with C. pneumoniae positivity (C. pneumoniae IgA and RT-PCR), suggesting thereby that C. pneumoniae may have caused chronic persistent infection in CAD. [source] Stereoselective Synthesis and Antiviral Activity of (1E,2Z,3E)-1-(Piperidin-1-yl)-1-(arylhydrazono)-2-[(benzoyl/benzothiazol- 2-oyl)hydrazono]-4-(aryl1)but-3-enesARCHIV DER PHARMAZIE, Issue 3 2010Hatem A. Abdel-Aziza Abstract The reaction of benzoyl hydrazine 1a or benzothiazole-2-carbohydrazide 1b with 2-oxo- N -arylpropanehydrazonoyl chlorides 2a,d yielded (1Z,2E)-2-[(benzoyl/benzothiazol-2-oyl)hydrazono]- N -(aryl)propanehydrazonoyl chlorides 3a,e. The reaction of 3a,c with sodium benzenesulphinate furnished sulphones 5a,c while the reaction of 5d, e with hydroxyl amine afforded hydroxomoyl derivatives 6a, b. The one-pot sterioselective reaction of N -(aryl)propanehydrazonoyl chlorides 3 with certain aromatic aldehydes in the presence of piperidine resulted in the formation of (1E,2Z,3E)-1-(piperidin-1-yl)-1-(arylhydrazono)-2-[(benzoyl/benzothiazol-2-oyl)hydrazono]-4-(aryl1)-but-3-enes 7a,g. X-ray analysis of piperidinyl amidrazone 7g showed a conversion of its geometrical structure with respect to that of compound 3 and confirmed the stereoselectivity of the latter reaction. The piperidinyl amidrazones 7a,g possessed a significant antiviral activity against herpes simplex viruses (HSV-1). Compound 7d reduced the number of viral plaques of herpes simplex type-1 (HSV-1) by 67%, with respect to the effect of reference drug Aphidicolin. [source] Synthesis and In-vitro Activity of 4,-Modified Analogues of ddA as Potent Anti-HIV AgentsARCHIV DER PHARMAZIE, Issue 10 2009Joon Hee Hong Abstract This paper reports the synthesis of novel 4,-hydrophobic pocket deoxythreosyl C-nucleosides. The key threose-like intermediates 9 and 14 were constructed from acyclic ketone derivatives, respectively. The antiviral activities of the synthesized compounds against the HIV-1, HSV-1, HSV-2, and HCMV viruses were evaluated. The 9-deaza-adenine derivatives 10 and 20 showed good anti-HIV activity without exhibiting significant cytotoxicity. [source] Effect of Protease Inhibitors on Yield of HSV-1-Based Viral VectorsBIOTECHNOLOGY PROGRESS, Issue 3 2000James B. Wechuck The ability to obtain high titer replication-defective herpes simplex virus (HSV) recombinant vectors will dramatically affect their use in gene therapy clinical trials. A variety of techniques and reagents have been employed to increase the overall yield of the vector. The effects of protease inhibitors on the yield of an HSV-1-based viral vector were examined. Experiments were conducted using a commercial protease inhibitor cocktail typically used in mammalian cell culture for protein production. Contrary to our expectation for enhanced vector yield, the results showed a dramatic reduction in vector yield. Moreover, it was found that AEBSF is the only component in the protease cocktail responsible for the low vector yield. On the basis of our hypothesis regarding the mode of action of AEBSF, we suggest that it should not be included in protease inhibitor cocktails designed for use in cultures aimed at production of viral vectors derived from HSV-1 or possibly several other vectors. [source] | ||||||||||||||||||||||||||||