herpes
Demonstration of either endogenous recurrence or exogenous reinfection by restriction endonuclease cleavage analysis of herpes simplex virus from patients with recrudescent genital herpes.

Sakaoka H, Aomori T, Gouro T, Kumamoto Y.

Department of Oral Bacteriology, Hokkaido University, Sapporo, Japan.

By using restriction endonuclease (RE) cleavage analysis, either endogenous recurrence or exogenous reinfection of herpes simplex virus (HSV) was clarified in 45 male and 20 female subjects with recrudescent genital herpes. All of the plural (two to ten) isolates from 63 (205 isolates) out of 65 subjects (97%) were HSV-2. Two isolates from only one of 65 subjects (1.5%) were HSV-1, and they showed the same RE profile. In addition, an HSV-1 and five HSV-2 isolates were obtained from the remaining one female patient (1.5%), indicating that an exogenous HSV-1 strain has been reinfected during HSV-2 recrudescences. HSV-2 isolates were furthermore classified into genotypes of HSV-2 using 16 different RE markers with five REs. Two hundred and ten HSV-2 isolates from 64 subjects were classified into 27 distinct genotypes, in which some predominant genotypes and seven new genotypes were found. Plural HSV-2 isolates obtained from 63 out of 64 subjects, including one subject from whom an HSV-1 and five HSV-2 strains were isolated, were classified into the same genotypes, indicating that they may be regarded as recrudescent genital herpes by the reactivation of the same endogenous strain. However, the RE profiles of two HSV-2 strains from the remaining one subject were different. Thus, it was finally found that only two out of 65 subjects (3%) were reinfected with exogenous strains. These results lead to the conclusion that almost all recrudescent genital herpes are due to the reactivation of an initially infected HSV-2 strain, and are occasionally due to reinfection with distinct HSV strains of either the same or a different type.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7595418&dopt=Abstract herpes medicine



herpes
Human herpes virus 6B origin-binding protein: DNA-binding domain and consensus binding sequence.

Inoue N, Pellett PE.

National Institute of Health, Tokyo, Japan.

We previously demonstrated by a DNA-binding assay that the human herpes virus 6B (HHV-6B) replication origin has a structure similar to those of alphaherpes viruses, although the HHV-6B and herpes simplex virus type 1 (HSV-1) origin-binding proteins (OBPs) and origins are not interchangeable. Here we describe additional properties of the interaction between HHV-6B OBP and the HHV-6B origin. Competitive electrophoretic mobility shift assays (EMSAs) with DNA duplexes containing single-base alterations allowed deduction of a consensus DNA sequence for HHV-6B-specific OBP binding, YGWYCWCCY, where Y is T or C and W is T or A, while that for HSV-1-specific binding was reported to be YGYTCGCACT. By EMSA, the HHV-6B OBP DNA-binding domain was mapped to a segment containing amino acids 482 to 770. However, in Southwestern (protein-DNA) blotting, the region sufficient for the DNA binding encompassed only amino acids 657 to 770. Similarly, Southwestern blotting showed that amino acids 689 to 851 of HSV-1 OBP had HSV-1 origin-binding activity, although this region was insufficient for origin binding in the EMSA. Although the longer DNA-binding domains identified by EMSA have marginal overall homology among HHV-6B and alphaherpes virus OBP homologs, the smaller regions sufficient for the binding observed by Southwestern blotting have significant similarity. From these results, we propose a hypothesis that the DNA-binding domain of herpes virus OBPs consists of two subdomains, one containing a conserved motif that contacts DNA directly, and another, less well conserved, that may modulate either the conformation or accessibility of the binding domain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7609026&dopt=Abstract herpes medicine



herpes
Identification of spinal interneurons antecedent to adrenal sympathetic preganglionic neurons using trans-synaptic transport of herpes simplex virus type 1.

Joshi S, Levatte MA, Dekaban GA, Weaver LC.

John P. Robarts Research Institute, University of Western Ontario, London, Canada.

Control of sympathetic preganglionic neurons appears to be mediated, in part, through polysynaptic pathways using spinal interneurons. To identify spinal interneurons antecedent to adrenal sympathetic preganglionic neurons, we injected herpes simplex virus type 1 into the adrenal gland of hamsters as this virus is an effective trans-synaptic tracer of neural pathways. After a three day survival period, immunocytochemistry was used to visualize virus-infected spinal cord cells. Infected sympathetic preganglionic neurons with somata that were either kite-shaped, elliptical or fusiform and that had extensive dendrite arbors were identified as well as a group of smaller round cells with finer processes. For comparison, in additional hamsters, labelling with the retrograde tracer Fluoro-Gold and histochemical reactions for the enzyme nicotinamide adenine dinucleotide phosphate-diaphorase were used to identify sympathetic preganglionic neurons. Sympathetic preganglionic neurons identified with Fluoro-Gold or herpes virus were present mostly in the nucleus intermediolateralis, pars intermediolateralis and nucleus intermediolateralis, pars funicularis of the spinal cord. The smaller herpes virus-infected cells were found mostly medial to the preganglionic neurons in lamina VII and also dorsally in lamina V of the spinal cord. Assessing immunoreactivity for glial fibrillary acidic protein demonstrated that the smaller herpes virus-infected cells were not reactive astrocytes. Furthermore, these cells were immunoreactive for two neuronal markers, neuron-specific enolase and for microtubule-associated protein 2. These findings suggest that these smaller round cells with finer processes are distinct from sympathetic preganglionic neurons and astrocytes and may be interneurons antecedent to the sympathetic preganglionic neurons.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7609886&dopt=Abstract herpes medicine



herpes
Rapid diagnosis of ocular herpes simplex infections.

Asbell PA, Torres MA, Kamenar T, Bottone EJ.

Department of Ophthalmology, Mount Sinai Medical Center, New York, USA.

BACKGROUND--The Surecell herpes (HSV) test kit is a test for detecting the presence of herpes simplex viral antigen by means of a monoclonal antibody based immunoassay. The test has proved to be highly sensitive and specific in diagnosing genital, oral, and dermatological herpes infections. METHODS--In this study, samples from patients with ocular keratitis were evaluated by tissue cultures and the Surecell test. The eyes of New Zealand rabbits were then inoculated with HSV type 1 acute keratitis, acute Staphylococcus keratitis, and HSV type 1 postkeratitis (healed corneas). Tear film samples collected from each eye with a cotton swab were evaluated by routine culture (A-549 monolayers) and by the Surecell test with and without prior placement of the swab in Hank's medium. RESULTS--The Surecell system had a 70% sensitivity and a 100% specificity in the detection of HSV antigen in ocular infections, and was shown to be a quick, efficient, and accurate method of testing for HSV antigen in humans. CONCLUSION--These results from humans and rabbits indicate that the Surecell test, which requires no special equipment, can be a useful in office adjunct in the clinical diagnosis of ocular herpes simplex.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7612561&dopt=Abstract herpes medicine



herpes
The incidence of herpes zoster.

Donahue JG, Choo PW, Manson JE, Platt R.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass., USA.

BACKGROUND: There are few population-based studies of the natural history and epidemiology of herpes zoster. Although a relatively common cause of morbidity, especially among the elderly, contemporary estimates of herpes zoster incidence are lacking. Herein we describe a population-based investigation of incident and recurrent herpes zoster from 1990 through 1992 in a health maintenance organization. METHODS: The health maintenance organization's automated medical records contain clinical and administrative information about care rendered to patients in ambulatory settings, emergency departments, and hospitals. Cases of herpes zoster were ascertained by screening the medical record for coded diagnoses. The predictive value of a herpes zoster diagnosis code was determined by review of a sample of patient records. Records from all patients with potential recurrences were also reviewed. RESULTS: The overall incidence, based on 1075 cases in 500,408 person-years, was 215 per 100,000 person-years (95% confidence interval, 192 to 240 per 100,000) and did not vary by gender. Although the rate increased sharply with age, approximately 5% of the cases occurred among children younger than 15 years. Infection with human immunodeficiency virus was documented in 5% of the persons with incident herpes zoster and cancer in 6%. Four persons had confirmed recurrences of herpes zoster (744 per 100,000 person-years; 95% confidence interval, 203 to 1907); three of these persons were infected with the human immunodeficiency virus. CONCLUSIONS: The recorded incidence of herpes zoster was 64% higher than that reported 30 years ago; the age-standardized rate was more than twofold higher. Immunosuppressive conditions had little impact on overall incidence, although they were strongly associated with early recurrences.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7618983&dopt=Abstract herpes medicine



herpes
Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murine immunosuppression model.

Field HJ, Tewari D, Sutton D, Thackray AM.

Centre for Veterinary Science, Cambridge University Veterinary School.

A mouse model of herpes simplex virus type 1 infection in an immunocompromised host was established by using cyclosporin-A to impair T-cell function. Following inoculation of herpes simplex virus type 1 into the skin of the ear pinna, cyclosporin-A prolonged virus replication in the skin and neural tissues compared with that in immunocompetent mice. This model was used to investigate the activity of famciclovir (FCV) and valaciclovir (VACV), which are oral products of the antiherpes virus agents penciclovir and acyclovir, respectively. Both prodrugs gave similar blood profiles of the antiherpes virus agents in normal and cyclosporin-treated mice. The compounds were administered by the oral route at 50 mg/kg per dose twice daily for 5 days. Both compounds were very effective at clearing infectious virus from the tissues despite the immunosuppression; FCV-treated animals cleared virus from the ear pinna more rapidly than VACV-treated animals. The areas under the concentration-time curve (AUC) for virus replication with time were reduced to 50 and 30% of control values for ear pinna and brain stem, respectively, with VACV therapy and to < 5% in both tissues by FCV. When treatment was continued to day 10, the reductions in AUC for ear and brain stem, respectively, were to 33 and 26% of control values with VACV and to < 3 and < 5% with FCV. However, on cessation of the antiviral treatment, there was a reproducible recurrence of infectious virus in the tissues obtained from VACV-treated mice. The recurrence of infectious virus was also evident after 10 days of treatment with VACV. In mice which had received FCV for 10 or 5 days, these was no resumption of virus replication in the ear pinna or brain stem. When dosing was reduced to once per day, both compounds were less effective at controlling the infection. Nevertheless, no recurrence of infectious virus was observed on cessation of FCV therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625798&dopt=Abstract herpes medicine



herpes
T-cell death by apoptosis in vertically human immunodeficiency virus-infected children coincides with expansion of CD8+/interleukin-2 receptor-/HLA-DR+ T cells: sign of a possible role for herpes viruses as cofactors?

Lauener RP, Huttner S, Buisson M, Hossle JP, Albisetti M, Seigneurin JM, Seger RA, Nadal D.

Division of Immunology/Hematology, University Children's Hospital, Zurich, Switzerland.

One mechanism proposed to play a role in T-cell depletion in human immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell death). We assessed whether apoptosis is related to activation of T cells in vivo and its possible triggers. DNA was extracted from peripheral blood mononuclear cells (PBMC) taken from 16 vertically HIV-infected children and 9 HIV-negative children born to HIV-positive mothers (controls) and tested by agarose gel electrophoresis for the presence of DNA fragments specific for apoptosis. Signs of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected children, but not in PBMC from the nine controls. Eleven of the 12 HIV-infected children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+ cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in 7 of 7 further tested patients. In none of the probands an increased (> 5%) proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during active infection with herpes viruses. To investigate the possible role of herpes viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr virus (EBV) as an example for a herpes virus usually acquired during childhood. In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in PBMC and/or tissues, indicating active EBV replication. By contrast, no increased burden of EBV was found in the four HIV-infected patients without apoptosis or in the controls. Our data indicate that in children the occurrence of apoptosis in HIV infection is closely related to activation of CD8+ T cells. Furthermore, primoinfection with or reactivation of herpes viruses, such as EBV, may substantially contribute to such T-cell activation and the ensuing apoptosis. Additional studies are warranted to evaluate the contribution of herpes virus-triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency syndrome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7632948&dopt=Abstract herpes medicine



herpes
Pseudorabies virus and equine herpes virus 1 share a nonessential gene which is absent in other herpes viruses and located adjacent to a highly conserved gene cluster.

Baumeister J, Klupp BG, Mettenleiter TC.

Institute of Vaccines, Federal Research Center Viurs Diseases of Animals, Tubingen, Germany.

We have determined the nucleotide sequence and transcriptional pattern of a group of open reading frames in the pseudorabies virus (PrV) genome located near the left end of the unique long region within BamHI 5' fragment at map positions 0.01 to 0.06. The 7,412-bp BamHI 5' fragment was found to contain five complete open reading frames and part of a sixth whose deduced amino acid sequences showed homology to the UL50 (partial), UL51, UL52, UL53, and UL54 gene products of herpes simplex virus type 1 (HSV-1) and corresponding genes identified in other alphaherpes viruses. Homologs to the UL55 and UL56 genes of HSV-1 were not detected. However, we identified a gene with homology only to the first open reading frame (ORF-1) of the equine herpes virus 1 strain Ab4 (E. A. Telford, M. S. Watson, K. McBride, and A. J. Davison, Virology 189:304-316, 1992). Northern blot analyses revealed unique mRNAs for the UL51, UL54, and ORF-1 genes and a set of 3'-coterminal mRNAs for the UL52 to UL54 genes. A PrV mutant lacking ORF-1 was isolated after deletion of ORF-1 coding sequences and insertion of a lacZ expression cassette. The ORF-1- PrV mutant was able to productively replicate in noncomplementing cells to levels similar to those of wild-type PrV, proving that ORF-1 is not essential for replication of PrV in cell culture. The conservation of this gene between PrV and equine herpes virus 1 documents the close evolutionary relationship between these animal herpes viruses and points to a possible function of the respective proteins in infection of the natural host.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7637001&dopt=Abstract herpes medicine