herpes
Screening for possible failure of herpes simplex virus PCR in cerebrospinal fluid for the diagnosis of herpes simplex encephalitis.

Puchhammer-Stockl E, Presterl E, Croy C, Aberle S, Popow-Kraupp T, Kundi M, Hofmann H, Wenninger U, Godl I.

Institute of Virology, University of Vienna, Vienna, Austria.

The objectives of this study were to evaluate the reliability of herpes simplex virus (HSV) PCR testing in cerebrospinal fluid (CSF) for the detection of herpes simplex encephalitis. This was done by examining retrospectively the clinical follow-up of a large group of patients tested routinely by HSV-PCR. In addition, an attempt was made to assess the incidence of herpes simplex encephalitis in a central European population. CSF samples from 1,427 patients from all Vienna hospitals were submitted for HSV-PCR testing during a period of 4 years and 8 months. Herpes simplex encephalitis was detected by PCR in 12 cases and by serological methods in one additional patient. Retrospective analysis of the course of disease, which was possible in 799 PCR-negative patients, led to the identification of three additional cases in which herpes simplex encephalitis appears to have occurred despite negative PCR results. Failure of the PCR in these patients is most likely due to the time of obtaining CSF during the course of disease. A high specificity of the assay was demonstrated by the lack of false positive results in any of the 708 cases in which other causes for the neurological symptoms had been identified in the follow-up. The incidence of herpes simplex encephalitis in the population of Vienna was between 1 case/469,000-577,000 individuals/year. The highest annual incidence was detected in the age group between 3 months and 3 years, which, however, could not be confirmed statistically. Copyright 2001 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11468740&dopt=Abstract herpes medicine



herpes
Mutations in the N-terminal domains of nectin-1 and nectin-2 reveal differences in requirements for entry of various alphaherpes viruses and for nectin-nectin interactions.

Struyf F, Martinez WM, Spear PG.

Department of Microbiology-Immunology, The Feinberg School of Medicine, Northwestern University, 320 E. Superior Street, Chicago, IL 60611, USA.

Nectin-1 and nectin-2 are related molecules that can function with different specificities as entry receptors for mammalian alphaherpes viruses through interaction with viral glycoprotein D (gD). The normal function of members of the nectin family is to mediate cell-cell adhesion through homotypic and heterotypic nectin-nectin interactions in cadherin-based adherens junctions. We examined mutations in three equivalent regions of the N-terminal V-like domains of nectin-1 and nectin-2 to test the effects on entry of various alphaherpes viruses, nectin-nectin interactions, and interactions of the mutant nectins with gD. Mutations in region I previously shown to severely impair herpes simplex virus (HSV) entry activity, but not pseudorabies virus (PRV) or bovine herpes virus 1 (BHV-1) entry, did not reduce homotypic trans interactions for either nectin-1 or nectin-2 or binding of nectin-3 to nectin-1. Mutations in region II, patterned after a reported single-nucleotide polymorphism in nectin-2, enhanced intracellular accumulation of both nectin-1 and nectin-2 and had a deleterious effect on all of the activities under study. Mutations in region III previously shown to reduce homotypic trans interactions of nectin-2 impaired the entry of PRV and BHV-1 when introduced into either nectin-1 or nectin-2, but only the nectin-2 mutation reduced HSV entry activity. Binding of nectin-1 to nectin-3 was not affected. Effects of the nectin-1 and nectin-2 mutations on interactions with gD did not necessarily correlate with entry activity of the mutant receptors. We can conclude that structural requirements for HSV entry, PRV and BHV-1 entry, and homotypic and heterotypic trans interactions are all different despite the previously reported ability of HSV and HSV gD to inhibit trans interactions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12438620&dopt=Abstract herpes medicine



herpes
Histological lesions in vascular tissues of bovine herpes virus type 4-infected rabbits.

Egyed L, Baska F.

Veterinary Medical Research Institute of the Hungarian Academy of Sciences, P.O. Box 18, H-1581 Budapest, Hungary. laci novell.vmri.hu

The gamma-herpes virus bovine herpes virus type 4 (BoHV-4) is distributed worldwide in cattle populations with unknown pathogenicity. Bovine endothelial cells were recently shown to be susceptible to BoHV-4 infection in vitro and this virus accelerated the cholesterol-induced atherosclerotic process in rabbits. In this study, the in vivo effect of BoHV-4 on cardiovascular tissue was investigated by intravenous infection of rabbits fed a cholesterol free diet. Inflammatory lesions of vascular tissue in aortic and valvular endothelial cells, and smooth muscle cells were detected by H&E staining, PCR, IF, EM immunohistochemistry, while virus isolation was used to detect virus particles. Acute and chronic vasculitis, signs of chronic endocarditis, with mononuclear cell accumulation and a fresh thrombus was found. Herpes viruses have already been thought to initiate cardio-vascular disorders, now this paper shows that a bovine gamma-herpes virus could also be a causative agent of vascular lesions in mammals fed a normal diet. BoHV-4-infection of rabbits could serve as a useful animal model for research into virus-induced human cardio-vascular diseases.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12441227&dopt=Abstract herpes medicine



herpes
Evaluating phenotype and genotype of drug-resistant strains in herpes viruses.

Andrei G, Fiten P, De Clercq E, Snoeck R, Opdenakker G.

Rega Institute for Medical Research, Katholieke Univ. Leuven, Leuven, Belgium. Graciela.Andrei rega.kuleuven.ac.be

The isolation of drug-resistant strains of herpes viruses, including Herpes Simplex Virus type I (HSV-1) and type 2 (HSV-2), Varicella-Zoster Virus (VZV), and cytomegalovirus (CMV), has been reported with increasing frequency in immunocompromised patients and is a matter of major concern. Determination of antiviral drug susceptibilities is a prerequisite for the management of drug-resistant herpes virus infections. Phenotyping studies should be correlated with genotyping, i.e., characterization of the mutations in the target genes. The isolation of drug-resistant virus in the laboratory and the determination of their phenotype and genotype may be useful to clarify the mechanisms of selective drug action. We describe here the procedures used for in vitro selection of drug-resistant herpes virus mutants and the determination of their patterns of drug-susceptibility. The subcloning of the HSV-1 DNA polymerase gene is described as an example of the methodology followed to determine the mutation(s) in the drug-target viral gene that are associated with the resistant phenotype. To avoid the introduction of mutations by PCR amplification, all subcloning experiments were executed directly on viral DNA. Viral DNA was prepared from each plaque-purified viral strain and a 3.4 kb BamHI fragment containing 87% of the HSV-1 DNA polymerase gene coding region was purified and further digested with SacI; the two resulting fragments were subcloned into pU18 and propagated in Escherichia coli. Plasmid DNA was isolated and the inserts were sequenced using dideoxynucleotide chain termination method with T7 DNA polymerase and Taq DNA polymerase in an automated laser fluorescent DNA sequencer. pUC/M13 reverse, universal primers and oligonucleodite primers based on the wild-type virus sequence were used. The nucleotide sequences of the DNA polymerase genes of the different mutants was then compared with the nucleotide sequence of the wild-type HSV-1 KOS strain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11471457&dopt=Abstract herpes medicine



herpes
[Clinical management of genital herpes: what can be done in pregnancy?]

[Article in French]

Braig S, Chanzy B.

Centre hospitalier de la region annecienne, BP 2333, 74011 Annecy, France.

Neonatal herpes infection is the major complication of genital herpes even if it occurs in less than 1/10,000 births. A great number of recent studies illustrates the natural history of genital herpes. The importance of viral transmission by asymptomatic shedding is now well established. The widespread use of viral diagnosis strategies is the prerequisite to efficient genital herpes prevention in order to eradicate viral mother-to-child transmission. This starts with the detection of at-risk situations such as primary infection in late pregnancy. Once the at-risk situation is known there should be concern about the adaptation of treatment strategies including antiviral therapy. The following work proposes different strategies facing each at-risk situation in order to discuss the efficiency of new diagnostic and treatment tools.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12469515&dopt=Abstract herpes medicine



herpes
Screening for neonatal herpes: physicians' descriptions of discussions with parents.

Cotton S, Connelly BL, Cohen SS, Siegel RM, Stanberry LR, Rosenthal SL.

Division of Adolescent Medicine, Children's Hospital Medical Center, Cincinnati, OH, USA. sxc130 po.cwru.edu

Screening for possible herpes simplex virus infection in neonates may raise feelings of anxiety and distress among parents and physicians. To elicit physicians' experiences of communicating with families when screening for neonatal herpes, we conducted a series of semi-structured interviews with 15 physicians from one paediatric institution, and coded the resulting audiotapes for common themes. These included how physicians prepared families for screening and treatment, how physicians managed stigma, and perceived parental reactions. Techniques for fostering good communication included being direct and honest and ensuring the time and place for discussion were appropriate; strategies for managing stigma included placing the diagnosis in epidemiological context, and discussing the potential severity of the disease. Physicians described many parental emotional reactions, some of which were herpes-specific, and suggested strategies to manage potential discomfort when discussing neonatal herpes with families. Future research can determine which strategies are most effective, which are associated with negative psychological outcomes, and how medical students and residents can be better trained to screen for this diagnosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12470602&dopt=Abstract herpes medicine



herpes
The potential role of suppressive therapy for sex partners in the prevention of neonatal herpes: a health economic analysis.

Barnabas RV, Carabin H, Garnett GP.

Nuffield Department of Medicine, University of Oxford, UK.

BACKGROUND: The development of suppressive therapy and type specific tests for herpes infections allow for screening to reduce the risk of neonatal herpes. OBJECTIVES: To assess the potential effectiveness, cost effectiveness, and benefit of suppressive therapy among herpes simplex virus serodiscordant sex partners during pregnancy. METHODS: Decision and economic analyses are used to compare the incidence and costs of neonatal herpes in California (2000) for three interventions: (1) no management; (2) current guidelines (caesarean delivery for women with lesions); (3) screening for women at risk and use of suppressive treatment in sex partners. RESULTS: Screening and suppressive therapy are the most effective interventions, while current guidelines have limited effectiveness, but the latter provide the most cost effective results. CONCLUSIONS: While current guidelines are cost saving, they forgo a potential 82% decrease in neonatal herpes incidence that would be possible with screening and suppressive therapy if society were willing to pay the necessary US$363 000 per case prevented. To evaluate HSV screening and drug therapy completely, clinical trials and an economic assessment of infant mortality "value" to society are required.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12473803&dopt=Abstract herpes medicine



herpes
Cytomegalovirus periodontal presence is associated with subgingival Dialister pneumosintes and alveolar bone loss.

Slots J, Sugar C, Kamma JJ.

University of Southern California, School of Dentistry, Los Angeles, CA 90089-0641, USA.

Destructive periodontal disease is associated with human cytomegalovirus (HCMV), Epstein-Barr type 1 virus (EBV-1) and other members of the Herpesviridae family as well as with various gram-negative anaerobic bacteria, including the Dialister pneumosintes species. This study aimed to determine possible interrelationships between periodontal HCMV, EBV-1, herpes simplex virus and D. pneumosintes, and relate the microbiological findings to periodontitis clinical status. Sixteen subjects each contributed paper point samples from two progressing and two stable periodontitis lesions, as determined by ongoing loss of probing attachment. Polymerase chain reaction methodology was used to identify the study herpes viruses and D. pneumosintes. Chi-squared tests, Fisher exact tests and multivariate logistic regression were employed to identify statistical associations among herpes viruses, bacteria and clinical variables. HCMV, and no other virus or combination of viruses, was positively associated with the presence of D. pneumosintes, and the relationship was specific for individual periodontitis sites with no detectable subject effect. D. pneumosintes was in turn positively associated with periodontal pocket depth and disease-active periodontitis. When the average percentage of alveolar bone loss in all teeth was treated as a response, HCMV remained significant even after D. pneumosintes was included in the model, suggesting that both HCMV and D. pneumosintes affected bone loss or, alternatively, HCMV affected factors not studied that themselves can induce bone loss. We hypothesize that periodontal HCMV sets the stage for subgingival proliferation of D. pneumosintes and subsequent periodontal disease progression. Studies on herpesviral-bacterial interactions may hold great promise for delineating important etio-pathogenic aspects of destructive periodontal disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12485328&dopt=Abstract herpes medicine



herpes
Thermoreversible gel as a candidate barrier to prevent the transmission of HIV-1 and herpes simplex virus type 2.

Piret J, Gagne N, Perron S, Desormeaux A, Tremblay MJ, Gourde P, Omar RF, Bergeron AM.

Centre de Recherche en Infectiologie, Universite Laval, Quebec, Quebec, Canada.

BACKGROUND: Sexually transmitted diseases (STDs) caused by HIV, herpes simplex virus (HSV), and other pathogens are spreading dramatically. The need to develop active products and vehicles to reduce this epidemic is urgent. GOAL: The efficacy of a thermoreversible gel formulation as a possible barrier to prevent the transmission of pathogens causing STDs was evaluated. STUDY DESIGN: This evaluation investigated the ability of the gel formulation to prevent infection of susceptible cells by HIV-1 and HSV-2 in vitro, the diffusion of radiolabeled herpes virus and micelles of polymer through an insertion membrane, and the electron microscopic appearance of herpes virus and gel alone or mixed together. RESULTS: The gel formulation prevents infection of susceptible cells by HIV-1 and HSV-2. It acts as an effective artificial physical barrier against the herpes virus within the first 4 hours of incubation. Herpes virus is coated by the gel or entrapped within micelles of the gel, which could hinder its attachment to target cells and inhibit its infectivity. CONCLUSION: This thermoreversible gel formulation represents an attractive matrix for the incorporation of microbicides to prevent the spread of STDs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11473223&dopt=Abstract herpes medicine