herpes
Herpesviruses and periodontopathic bacteria in Trisomy 21 periodontitis.

Hanookai D, Nowzari H, Contreras A, Morrison JL, Slots J.

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

BACKGROUND: Little is known about the etiology and pathogenesis of periodontal disease in Trisomy 21 patients. This study determined the occurrence of herpes viruses and putative periodontopathic bacteria in Trisomy 21 periodontitis. METHODS: Nineteen Trisomy 21 patients (17 to 37 years of age) contributed subgingival samples from molar and bicuspid teeth presenting interproximal periodontitis lesions (probing depths, 5 to 8 mm) and from shallow periodontal sites (probing depths, 1 to 3 mm). Samples were obtained at baseline, and at 1 and 4 weeks after subgingival debridement by means of hand instruments and ultrasonic scalers. Epstein-Barr virus type 1 and 2 (EBV-1 and EBV-2), human cytomegalovirus (HCMV), and herpes simplex virus (HSV) were identified by sensitive and specific nested polymerase chain reaction. Putative periodontopathic bacteria were identified by means of non-selective and selective culture. RESULTS: Of 19 Trisomy 21 periodontitis lesions, 6 (32%) were positive for EBV-1, 5 (26%) were positive for HCMV, 3 (16%) were positive for HSV, and 2 (11%) showed viral co-infection. Of 19 shallow periodontal sites, only one revealed HCMV. Prevotella intermedia, Bacteroides forsythus, and Capnocytophaga species were detected in higher proportions in deep than in shallow periodontal pockets (P = 0.02). Subgingival debridement did not reduce genomic herpes virus presence but caused a decrease in proportions of Porphyromonas gingivalis and Capnocytophaga species. CONCLUSIONS: Periodontal herpes virus-bacteria coinfections may play important roles in the pathogenesis of destructive periodontal disease in Trisomy 21 patients. Herpesviruses may reduce the periodontal defense and promote growth of subgingival bacteria capable of causing periodontal breakdown.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10776924&dopt=Abstract herpes medicine



herpes
The murine homolog of human Nectin1delta serves as a species nonspecific mediator for entry of human and animal alpha herpes viruses in a pathway independent of a detectable binding to gD.

Menotti L, Lopez M, Avitabile E, Stefan A, Cocchi F, Adelaide J, Lecocq E, Dubreuil P, Campadelli-Fiume G.

Department of Experimental Pathology, Section on Microbiology and Virology, University of Bologna, Via San Giacomo, 12, 40126 Bologna, Italy.

The full-length cDNA of the murine homolog of human nectin1delta (mNectin1delta), also known as human poliovirus receptor related 1 (PRR1) or herpes virus entry mediator C, was cloned and showed a >90% identity with its human counterpart. mNectin1delta is expressed in some murine cell lines, exemplified by NIH 3T3 and L cells, and in murine tissues. It mediates entry of an extended range of herpes simplex virus (HSV) strains, porcine pseudorabies virus (PrV), and bovine herpes virus 1. A soluble form of the mediator blocked infectivity in mNectin1delta and human nectin1delta (hNectin1delta)-expressing cells, suggesting a physical interaction of the mediator with virions. The higher concentrations of soluble mNectin1 required to block infectivity relative to soluble hNectin1 suggest that the target of the two molecules is not identical. Entry of HSV, but not PrV, was blocked by soluble mNectin1delta in NIH 3T3 and L cells. Two features were unexpected. First, soluble mNectin1delta failed to physically interact with HSV glycoprotein D (gD) at a detectable level, although it interacted physically with virions. Second, coexpression of mNectin1delta and HSV gD did not restrict HSV or PrV infection, whereas coexpression of hNectin and gD did restrict infection, suggesting that mNectin1delta fails to be sequestered by HSV gD. We conclude that mNectin1delta serves as a species-nonspecific mediator for entry of the human and animal alphaherpes viruses. This activity, at least for HSV, is independent of a detectable binding to gD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10781093&dopt=Abstract herpes medicine



herpes
Herpes simplex replication and dissemination is not increased by corticosteroid treatment in a rat model of focal Herpes encephalitis.

Thompson KA, Blessing WW, Wesselingh SL.

Infectious Diseases Unit, School of Medicine, Monash University, Victoria, Australia.

Neurological damage in Herpes simplex type 1 encephalitis results from neuronal cell death secondary to viral invasion, and from inflammatory changes and cerebral oedema secondary to the immune response to the virus. Corticosteroids could have an important role in the management of Herpes simplex encephalitis because their anti-inflammatory action reduces cerebral oedema. However their use has been limited by concerns that their immunosuppressive actions could increase viral replication and spread. The present study examined this issue in a rat model in which injection of HSV-1 into the cervical vagus nerve produced a well-defined focal encephalitis, characterised by an orderly progression of the virus through central neural pathways connected with vagal afferent termination sites in the medulla oblongata. After injection of HSV-1, rats were treated twice a day, either with vehicle (saline, 400 microl i.p.), with acyclovir (30 mg/kg i.p.), with dexamethasone (5 mg/kg i.p.), or with both acyclovir and dexamethasone. Animals were sacrificed after 72 h, and viral load in different brain regions was quantified by computer-assisted measurement of the area occupied by immunohistochemical reaction product. Treatment with acyclovir reduced viral load to 17 +/- 5% of the saline value (P < 0.01). After dexamethasone treatment, the viral load (63 +/- 13% of the saline value) was also reduced (P < 0.05). Treatment with both acyclovir and dexamethasone reduced viral load to 26 +/- 8% of the saline value (P < 0.01 compared with saline, and P > 0.05 compared to acyclovir alone). Our results confirm the effectiveness of acyclovir in a new model of HSV-1 infection, and provide evidence that corticosteroids do not inhibit the antiviral action of acyclovir. In addition corticosteroids may decrease the extent of infection in their own right. The acute time course studied in our model parallels the time course of acute Herpes simplex encephalitis in humans. Our data suggests that corticosteroids are not detrimental when combined with acyclovir in the management of this condition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10786994&dopt=Abstract herpes medicine



herpes
Herpesvirus in localized juvenile periodontitis.

Ting M, Contreras A, Slots J.

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

Herpesvirus genomic sequences can be detected in gingival crevicular fluid of adult periodontitis lesions. Herpesviruses are immunosuppressive and may facilitate establishment of subgingival pathogens. Electron microscopic studies have identified nuclear and cytoplasmic virus-like inclusions in gingival inflammatory cells from localized juvenile periodontitis (LJP). The present study aimed to determine if herpes viruses occur in LJP lesions and if human cytomegalovirus (HCMV) activation is associated with elevated levels of subgingival Actinobacillus actinomycetemcomitans, the putative bacterial pathogen of LJP. Eleven systemically healthy patients exhibiting LJP (10-23 yr) were studied. In each patient, subgingival samples were pooled from 3 periodontitis lesions around first molar and incisor teeth (5-11 mm periodontal pocket depth) and from 3 gingivitis/healthy sites around canines (2-3 mm periodontal pocket depth). Polymerase chain reaction (PCR) was used to detect herpes virus DNA and HCMV cDNA of major capsid protein transcripts, indicative of viral activation. Selective culture and 16S rRNA PCR were used to identify A. actinomycetemcomitans. Of 11 deep periodontal samples, 8 showed HCMV, 7 showed Epstein-Barr virus type 1 (EBV-1), 1 showed EBV type 2, 6 showed herpes simplex virus (HSV) and 8 showed viral co-infection. Of 11 shallow periodontal samples, 2 showed HCMV, 2 showed EBV-1, 1 showed HSV and 2 showed viral co-infection. The difference in occurrence of HCMV and viral co-infection between deep and shallow periodontal sites was statistically significant (p =0.031). HCMV activation was detected in deep pockets of all 5 virally positive patients with early LJP (aged 10-14 years) but only in 1 of 3 virally positive LJP patients older than 14 years, and not in any shallow pocket tested. HCMV activation appeared related to absence of radiographic crestal alveolar lamina dura, a possible indication of periodontal disease progression. A. actinomycetemcomitans tended to be more prevalent in samples showing active than latent HCMV infection. The present findings are consistent with the notion that periodontal herpes virus infection and possibly HCMV activation constitute important features of the etiopathogenesis of LJP.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10791705&dopt=Abstract herpes medicine



herpes
Herpesviruses in brain and Alzheimer's disease.

Lin WR, Wozniak MA, Cooper RJ, Wilcock GK, Itzhaki RF.

Department of Optometry and Neuroscience, UMIST, Manchester, UK.

It has been established, using polymerase chain reaction (PCR), that herpes simplex virus type 1 (HSV1) is present in a high proportion of brains of elderly normal subjects and Alzheimer's disease (AD) patients. It was subsequently discovered that the virus confers a strong risk of AD when in brain of carriers of the type 4 allele of the apolipoprotein E gene (apoE-epsilon4). This study has now sought, using PCR, the presence of three other herpes viruses in brain: human herpes virus 6 (HHV6)-types A and B, herpes simplex virus type 2 (HSV2) and cytomegalovirus (CMV). HHV6 is present in a much higher proportion of the AD than of age-matched normal brains (70% vs. 40%, p=0.003) and there is extensive overlap with the presence of HSV1 in AD brains, but HHV6, unlike HSV1, is not directly associated in AD with apoE-epsilon4. In 59% of the AD patients' brains harbouring HHV6, type B is present while 38% harbour both type A and type B, and 3% type A. HSV2 is present at relatively low frequency in brains of both AD patients and normals (13% and 20%), and CMV at rather higher frequencies in the two groups (36% and 35%); in neither case is the difference between the groups statistically significant. It is suggested that the striking difference in the proportion of elderly brains harbouring HSV1 and HSV2 might reflect the lower proportion of people infected with the latter, or the difference in susceptibility of the frontotemporal regions to the two viruses. In the case of HHV6, it is not possible to exclude its presence as an opportunist, but alternatively, it might enhance the damage caused by HSV1 and apoE-epsilon4 in AD; in some viral diseases it is associated with characteristic brain lesions and it also augments the damage caused by certain viruses in cell culture and in animals. Copyright 2002 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12115887&dopt=Abstract herpes medicine



herpes
Seroprevalence and determinants of herpes simplex type 2 infection in an STD clinic in Milan, Italy.

Suligoi B, Calistri A, Cusini M, Palu G; Italian Herpes Management Forum.

Reparto AIDS e MST, Istituto Superiore di Sanita, Rome, Italy. suligoi iss.it

A number of studies have shown that the seroprevalence of herpes simplex virus type 2 (HSV-2) is higher among persons attending clinics for sexually transmitted diseases (STD) than among the general population. The HSV-2 seroprevalence among STD patients, however, varies greatly among studies, possibly reflecting differences in the baseline prevalence of the infection among different general populations or in the distribution of risk factors. A cross-sectional study was carried out to determine the seroprevalence of and the risk factors for HSV-2 infection among 776 HIV-negative persons attending an STD clinic in Milan, Italy. All samples were tested with a commercial HSV type-2 specific gG ELISA test. The HSV-2 seroprevalence was 29.5% (95% CI: 26.3-32.7%). The seroprevalence increased with age, yet it did not differ by gender. Among persons with a current STD, the seroprevalence was 44.3%. At the multivariate analysis, older age was independently associated with HSV-2 infection. A self-reported history of genital herpes was predictive of HSV-2 infection. The agreement between history of genital herpes and HSV-2 seroprevalence was poor, however, stressing that in clinical practice, caution should be used in interpreting the presence or absence of a history of genital herpes as an indicator of the presence or absence of HSV-2 infection. Our data show that HSV-2 seroprevalence among persons attending an STD clinic in Italy is high; thus serological screening for HSV-2 might be advisable for STD patients. Copyright 2002 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12116025&dopt=Abstract herpes medicine



herpes
HSV-2 specific serology should be offered routinely to antenatal patients.

Brown ZA.

Department of Obstetrics and Gynecology, University of Washington, Seattle 98195-6460, USA.

The most devastating consequence of genital herpes is neonatal herpes. It is clear that the majority of newborns acquire their infection by contact with infected genital secretions during delivery from an asymptomatic mother who acquired a first episode of genital herpes near the time of labour. Since the majority of cases of first episode genital herpes during pregnancy are unrecognised, the prevention of neonatal transmission will depend upon the identification of the HSV serologically discordant couple and the institution of appropriate interventions by mid pregnancy. Therefore, the precis of this discussion paper is that universal HSV serological testing should be performed at the first prenatal visit. As a corollary, type specific HSV serology will need to be commercially available and relatively inexpensive. In any country, pregnant women and their partners represent a broad, cross section of sexually active adults. The vast majority present themselves to the health care system for care during their pregnancies which is a period of time in which the focus of care is primarily preventive and during which women are generally motivated and compliant. This is truly the 'golden opportunity' to identify patients already infected as well as those at risk for acquiring genital herpes. Information regarding genital herpes and methods of preventing transmission to susceptible partners and newborn infants can easily be added to educational programmes which have already become an institution within prenatal care. Copyright 2000 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10815025&dopt=Abstract herpes medicine



herpes
Epidemiology of primary varicella and herpes zoster hospitalizations: the pre-varicella vaccine era.

Lin F, Hadler JL.

Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA.

To determine the epidemiology and costs of hospitalization with primary varicella and herpes zoster in the prevaccine era and the usefulness of hospital discharge data to determine the population impact of vaccination on these conditions, statewide hospital discharge data in Connecticut from 1986 to 1995 were analyzed. Annual hospitalizations for herpes zoster were 4-fold higher than for primary varicella (16.1 vs. 4.1/100,000). Overall, 69% and 83%, respectively, had no underlying immunosuppressive conditions. Regarding primary varicella, 53% of patients were aged <15 years, there was a marked winter-spring seasonality, and Hispanics and blacks were 4.1 and 2.6 times more likely than whites to be hospitalized. Regarding herpes zoster, 66.9% of patients were aged >64 years, and there was no seasonality. The mean patient charges in 1995 were $12,819 for primary varicella and $15,583 for herpes zoster. Analysis of population-based hospital discharge data is a feasible means of monitoring the impact of varicella immunization on severe morbidity due to primary varicella and herpes zoster.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10837168&dopt=Abstract herpes medicine