herpes
Absence of herpes virus DNA by polymerase chain reaction in ocular fluids obtained from immunocompetent patients.

Pendergast SD, Werner J, Drevon A, Wiedbrauk DL.

Retina Associates of Cleveland, Inc., Beachwood, Ohio, USA.

OBJECTIVE: To assess the prevalence of herpes virus DNA in ocular fluids obtained from healthy patients undergoing vitreoretinal surgery. BACKGROUND: Polymerase chain reaction (PCR) has been used to detect herpes virus DNA in patients with acute retinal necrosis and cytomegalovirus retinitis. Little is known regarding the prevalence of detectable herpes virus DNA in ocular fluids collected from healthy seropositive patients with no clinical evidence of viral retinitis. METHODS: Seventy-five intraocular specimens (35 aqueous and 40 vitreous samples) were collected from 75 patients undergoing scleral buckling or vitrectomy. Using a PCR-based assay, the authors tested each specimen for the presence of herpes virus genome DNA with primers specific for cytomegalovirus, Epstein-Barr virus, herpes simplex virus types 1 and 2, and varicella zoster virus. Serologic testing for immunoglobulin G (IgG) and IgM levels corresponding to each of the herpes viruses was also performed. RESULTS: Of the 75 samples tested, none was found to harbor herpes virus DNA. The assay did not give false-positive results in patients with active intraocular inflammation. The sensitivity of the assay was 0.08 infection-forming units for cytomegalovirus, 0.6 tissue culture infectious doses for herpes simplex virus, 0.5 infected-cell equivalents for Epstein-Barr virus, and 0.03 focus-forming units for varicella zoster virus. The percentage of patients with positive herpes virus serology ranged from 86% to 100% and was consistent with rates observed in the general population. CONCLUSIONS: The prevalence of herpes virus DNA detectable by PCR techniques in ocular fluids appears to be quite low despite the high proportion of patients who tested positive for herpes virus antibodies. Therefore, a positive result obtained in a patient presenting with vitreoretinal inflammation should be regarded as significant.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10950418&dopt=Abstract herpes medicine



herpes
First episodes of genital herpes in a Swedish STD population: a study of epidemiology and transmission by the use of herpes simplex virus (HSV) typing and specific serology.

Lowhagen GB, Tunback P, Andersson K, Bergstrom T, Johannisson G.

Department of Dermatology, Sahlgrenska University Hospital, Goteborg, Sweden. Gun-Britt.Lowhagen sahlgrenska.se

OBJECTIVES: To determine the proportion of herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2) in first episodes of genital herpes. To evaluate the use of HSV specific serology for classifying first episodes of genital herpes and for defining HSV serostatus in the patients' sexual partners. METHODS: 108 consecutive patients with first episodes of genital herpes seen at three STD clinics in Sweden from 1995 to 1999 were included in the study. HSV culture and typing were performed and serum was tested for antibodies against a type common HSV antigen and a type specific HSV-2 antigen, glycoprotein G2 (gG2). A structured interview including questions about sexual behaviour and sexual partners was taken. "Steady" partners were offered a blood test for HSV serology and counselling. RESULTS: Of 108 patients, 11 had a negative HSV culture. Of the 97 who were HSV culture positive, 44% (43/97) were typed as HSV-1 and 56% (54/97) as HSV-2. For 86 of these 97 patients, HSV serology from the initial visit was available. Of 52 primary infections, thus initially seronegative, 64% were HSV-1 infections and of 19 female primary infections 16 (84%) were HSV-1. In 17% the first episode of genital herpes corresponded to the first clinical recurrence of an infection acquired earlier in life. There was a significant correlation between having orogenital sex and being infected with HSV-1 and also a history of labial herpes in the partner. Only 20% of partners of patients with an HSV-2 infection had a history of genital herpes. CONCLUSIONS: Almost half of first episodes of genital herpes are caused by HSV-1. In young women with a primary genital infection, HSV-1 is much more frequent than HSV-2. Besides HSV typing, we found specific HSV serology of value for classifying first episodes and for diagnosing a subclinical HSV-2 infection in partners. Anamnestic data supported the suggestion that the orogenital route of transmission was common in genital HSV-1 infections.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10961194&dopt=Abstract herpes medicine



herpes
[Detection of viral genomes of the Herpesviridae family in multiple sclerosis patients by means of the polymerase chain reaction (PCR)]

[Article in Spanish]

Alvarez R, Cour I, Kanaan A, Benedicto M, Martin-Estefania C, Arroyo R, Varela de Seijas E, Picazo JJ.

Servicio de Microbiologia, Hospital Universitario San Carlos, Madrid.

BACKGROUND: The multiple sclerosis seems to be the junction between genetics alteration and an unknown environmental factor, that they would originate an autoimmune alteration, that they would be the reason of the inflammation and demyelinization responsible of the disease. Our objective has been the determination of this possible environmental factor and to reach it, we have studied the appearance of Herpesviridae family viruses. MATERIALS AND METHODS: 204 blood samples were studied: 102 from relapsing-remitting multiple sclerosis patients (43 were undergoing beta-interferon treatment), and 102 from blood donors with the same age and sex than multiple sclerosis patients. From this samples, we extracted the DNA of peripheral blood mononuclear cells (PBMCs), and we analyzed by polymerase chain reaction (PCR) to detect the appearance of herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, human herpes virus 6 (HHV-6), human herpes virus 7 and human herpes virus 8. RESULTS: a) we only found significative difference (p = 0.0001) in HHV-6: 21.5% donors positive samples (22/102), opposite to 49.02% of positivity in mulytiple sclerosis patients (50/102); b) we didn't found significative differences in none of other viruses studied, between patients treated with beta-interferon and non-treated ones. CONCLUSIONS: Our results suggest us that HHV-6 can play an important role in the multiple sclerosis development. The beta-interferon treatment doesn't affect to DNA prevalence of none of studied viruses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10974766&dopt=Abstract herpes medicine



herpes
Three-dimensional structure of the human herpes virus 8 capsid.

Wu L, Lo P, Yu X, Stoops JK, Forghani B, Zhou ZH.

Viral and Rickettsial Disease Laboratory, Division of Communicable Disease Control, California Department of Health Services, Berkeley, California 94720, USA.

Human herpes virus 8 (HHV-8), or Kaposi's sarcoma-associated herpes virus, is a gammaherpes virus implicated in all forms of Kaposi's sarcoma and certain lymphomas. HHV-8 has been extensively characterized, both biochemically and immunologically, since its first description in 1994. However, its three-dimensional (3D) structure remained heretofore undetermined largely due to difficulties in viral purification. We have used log-phase cultures of body cavity-based lymphoma 1 cells induced with 12-O-tetradecanoylphorbol-13-acetate to obtain HHV-8 capsids for electron cryomicroscopy and computer reconstruction. The 3D structure of the HHV-8 capsids revealed a capsid shell composed of 12 pentons, 150 hexons, and 320 triplexes arranged on a T=16 icosahedral lattice. This structure is similar to those of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV), which are prototypical members of alpha- and betaherpes viruses, respectively. The inner radius of the HHV-8 capsid is identical to that of the HSV-1 capsid but is smaller than that of the HCMV capsid, which is consistent with the relative sizes of the genomes they enclose. While the HHV-8 capsid exhibits many structural similarities to the HSV-1 capsid, our reconstruction shows two major differences: its hexons lack the "horn-shaped" VP26 densities bound to the HSV-1 hexon subunits, and the HHV-8 triplexes appear smaller and less elongated than those of HSV-1. These differences are in excellent agreement with our sequence comparisons of HHV-8 and HSV-1 capsid proteins. This gammaherpes virus capsid structure complements previous structural studies on alpha- and betaherpes viruses in providing an account of structural similarities and differences among capsids representing all human herpes virus subfamilies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11000237&dopt=Abstract herpes medicine



herpes
Prevalence of postherpetic neuralgia after a first episode of herpes zoster: prospective study with long term follow up.

Helgason S, Petursson G, Gudmundsson S, Sigurdsson JA.

Arbaer Health Care Centre, IS-110 Reykjavik, Iceland. S.Helgason sh centrum.is

OBJECTIVE: To estimate the frequency, duration, and clinical importance of postherpetic neuralgia after a single episode of herpes zoster. DESIGN: Prospective cohort study with long term follow up. SETTING: Primary health care in Iceland. PARTICIPANTS: 421 patients with a single episode of herpes zoster. MAIN OUTCOME MEASURES: Age and sex distribution of patients with herpes zoster, point prevalence of postherpetic neuralgia, and severity of pain at 1, 3, 6, and 12 months and up to 7.6 years after the outbreak of zoster. RESULTS: Among patients younger than 60 years, the risk of postherpetic neuralgia three months after the start of the zoster rash was 1.8% (95% confidence interval 0.59% to 4.18%) and pain was mild in all cases. In patients 60 years and older, the risk of postherpetic neuralgia increased but the pain was usually mild or moderate. After three months severe pain was recorded in two patients older than 60 years (1.7%, 2.14% to 6.15%). After 12 months no patient reported severe pain and 14 patients (3.3%) had mild or moderate pain. Seven of these became pain free within two to seven years, and five reported mild pain and one moderate pain after 7.6 years of follow up. Sex was not a predictor of postherpetic neuralgia. Possible immunomodulating comorbidity (such as malignancy, systemic steroid use, diabetes) was present in 17 patients. CONCLUSIONS: The probability of longstanding pain of clinical importance after herpes zoster is low in an unselected population of primary care patients essentially untreated with antiviral drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11009518&dopt=Abstract herpes medicine



herpes
Rat cytomegalovirus R89 is a highly conserved gene which expresses a spliced transcript.

Gruijthuijsen YK, Beuken E, Bruggeman CA, Vink C.

Department of Medical Microbiology, Cardiovascular Research Institute Maastricht, University of Maastricht, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.

In all sequenced herpes virus genomes, a homolog of the herpes simplex virus type 1 UL15 gene has been identified. This gene encodes a protein that is involved in viral genome maturation. Although transcription of the alphaherpes virus UL15 gene has been analyzed in detail, not much is known about the expression of its betaherpes virus homologs. We therefore set out to characterize transcription of the rat cytomegalovirus counterpart of UL15, R89. Here we report that R89 consists of two exons separated by a 4.7-kb intron. The spliced R89 transcript, which is expressed at late times postinfection (p.i.), has the capacity to encode a protein of 670 amino acids with a calculated molecular mass of 77.1 kDa. The predicted amino acid sequence of this protein is highly similar to that of the proteins predicted to be encoded by the human cytomegalovirus UL89 and murine cytomegalovirus M89 genes (64.3 and 84.5% overall identity, respectively). The region between R89 exon 1 and exon 2 was found to contain five additional genes, r90, R91, R92, R93 and R94, the latter two of which are conserved among all herpes viruses. We show that these genes are transcribed in a highly complex fashion, resulting in numerous mono- and polycistronic mRNAs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11018281&dopt=Abstract herpes medicine



herpes
Effect of preexisting anti-herpes immunity on the efficacy of herpes simplex viral therapy in a murine intraperitoneal tumor model.

Lambright ES, Kang EH, Force S, Lanuti M, Caparrelli D, Kaiser LR, Albelda SM, Molnar-Kimber KL.

Thoracic Oncology Research Laboratory, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.

HSV-1716, a replicating nonneurovirulent herpes simplex virus type 1, has shown efficacy in treating multiple types of human tumors in immunodeficient mice. Since the majority of the human population has been previously exposed to herpes simplex virus, the efficacy of HSV-based oncolytic therapy was investigated in an immunocompetent animal tumor model. EJ-6-2-Bam-6a, a tumor cell line derived from h-ras-transformed murine fibroblast, exhibit a diffuse growth pattern in the peritoneal cavity of BALB/c mice and replicate HSV-1716 to titers observed in human tumors. An established intraperitoneal (ip) tumor model of EJ-6-2-Bam-6a in naive and HSV-immunized mice was used to evaluate the efficacy of single or multiple ip administrations of HSV-1716 (4 x 10(6) pfu/treatment) or of carrier cells, which are irradiated, ex vivo virally infected EJ-6-2-Bam-6a cells that can amplify the viral load in situ. All treated groups significantly prolonged survival versus media control with an approximately 40% long-term survival rate (cure) in the multiply treated, HSV-naive animals. Prior immunization of the mice with HSV did not significantly decrease the median survival of the single or multiply treated HSV-1716 or the carrier cell-treated groups. These studies support the development of replication-selective herpes virus mutants for use in localized intraperitoneal malignancies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11020355&dopt=Abstract herpes medicine



herpes
[Incidence of herpes neonatorum in Netherlands]

[Article in Dutch]

Gaytant MA, Steegers EA, van Cromvoirt PL, Semmekrot BA, Galama JM.

Afd. Obstetrie en Gynaecologie, Universitair Medisch Centrum St Radboud, Nijmegen. j.galama mmb.azn.nl

OBJECTIVE: Investigation of the incidence of neonatal herpes in the Netherlands between 1992 and 1998. DESIGN: Inventory questionnaire survey. METHODS: All virological laboratories in the Netherlands were sent a questionnaire on the number of culture proven cases of neonatal herpes recorded between 1992 and 1998 and on the type of herpes simplex virus (HSV-1 or HSV-2). The gynaecological and paediatric departments of all university hospitals and of half of the general hospitals were sent questionnaires as well. Gynaecologists were asked how often caesarean section was performed in order to prevent neonatal herpes and how frequently pregnant women were seen with genital herpes. Paediatricians were asked how often they observed neonatal herpes, the type of HSV and the possible transmission route. Based on these data the figures for the whole of the Netherlands were estimated. RESULTS: The incidence of neonatal herpes in the Netherlands in the period 1992 to 1998 was 2.4 per 100,000 neonates. HSV-1 was the cause of neonatal herpes in 73%, HSV-2 in 9%, and in 18% of the cases the type of infection was not recorded. The number of pregnant women with genital herpes had increased, but, in agreement with a consensus statement, the gynaecologists hardly performed caesarean sections any more to prevent neonatal herpes (2 per year). CONCLUSIONS: The incidence of neonatal herpes in the Netherlands had not increased. There was no predominant role of HSV type 2 causing neonatal herpes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11020838&dopt=Abstract herpes medicine