herpes
The antiherpes virus activity of H2G [(R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine] is markedly enhanced by the novel immunosuppressive agent mycophenolate mofetil.

Neyts J, Andrei G, De Clercq E.

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. johan.neyts rega.kuleuven.ac.be

Mycophenolate mofetil (MMF) has been approved as an immunosuppressive agent in kidney transplant recipients and may thus be used concomitantly with antiherpetic agents, which are used for the treatment of intercurrent herpes virus infections. We have recently demonstrated that MMF and its parent compound mycophenolic acid (MPA), which is a potent inhibitor of IMP dehydrogenase, potentiate the antiherpes virus activity of acyclovir, ganciclovir, and penciclovir. We have now evaluated the antiviral efficacy of the combination of MPA and the novel antiherpes virus agent H2G [(R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine]. When combined with H2G, MPA (at concentrations ranging from 0.25 to 10 microgram/ml, which are readily attainable in human plasma) markedly potentiated the antiviral efficacy of H2G against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), as reflected by a 10- to 150-fold decrease in the 50% effective concentration. Moreover, the activity of H2G against a thymidine kinase-deficient strain of HSV-1 (TK- HSV-1) was increased more than 2,500-fold when combined with MPA. MPA by itself had little or no effect on the replication of these viruses. Similar observations were made for varicella-zoster virus. Also, ribavirin (another inhibitor of IMP dehydrogenase) caused a marked enhancement of the activity of H2G against HSV-1 (10-fold), HSV-2 (10-fold), and TK- HSV-1 (>185-fold). Exogenously added guanosine reversed the potentiating effects of MPA on the antiviral activity of H2G, indicating that this potentiating effect resulted from a depletion of the endogenous dGTP pools, thus favoring the inhibitory action of the H2G triphosphate on the viral DNA polymerase.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9835529&dopt=Abstract herpes medicine



herpes
[Etiological diagnosis and classification of Herpes virus-associated disturbances of the central nervous system]

[Article in Ukrainian]

Kononenko VV.

An etiological classification is submitted of Herpes virus-induced affections of the central nervous system (CNS), such as monoherpesviral, herpes virus-bacterial, herpes virus-spirochetal, herpes virus-mycotic, herpes virus-protozoan affections. Excerpts from case records of etiologically confirmed mixed infections are given. Consideration is given to such herpes viruses as HSV, CMV, EBV, VZV. Other possible combinations of etiological agents include herpes virus + chlamidia, mycoplasms, prions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11881374&dopt=Abstract herpes medicine



herpes
Comparison of the sensitivity of a 24 h-shell vial assay, and conventional tube culture, in the isolation of Herpes simplex virus - 1 from corneal scrapings.

Athmanathan S, Bandlapally S, Rao GN.

Jhaveri Microbiology Center, Hyderabad Eye Research Foundation, L, V, Prasad Eye Institute, L, V, Prasad Marg, Banjara Hills, Hyderabad - 500 034, A, P, India. sreedhar lvpeye.stph.net

BACKGROUND: Herpes simplex keratitis is a sight threatening ocular infection. A rapid and specific diagnosis is essential for the institution of specific antiviral therapy and to avoid complications that can arise from misdiagnosis and inappropriate treatment. Though a variety of techniques are available, isolation of Herpes simplex virus 1 (HSV-1) in culture provides the most reliable and specific method, and is considered as the gold standard in laboratory diagnosis of herpes simplex keratitis. We report a comparative study of the sensitivity of a 24 h-shell vial assay and conventional tube culture in the isolation of HSV-1 from corneal scrapings. METHODS: A total of 74 corneal scrapings obtained from 74 patients with a clinical suspicion of herpes simplex keratitis submitted for the isolation of HSV-1, were simultaneously inoculated into shell vial and tube cultures employing the vero cell line. Shell vial and tube cultures were terminated at 24 h and fifth day respectively. Isolation of HSV-1 was confirmed employing an indirect immunofluorescence assay. RESULTS: HSV-1 was isolated from 24/74 (32.4%) specimens employing both the methods. Sensitivity of both the techniques were found to be similar (20/24, 83.3%) (P = 1.0). CONCLUSION: A 24 h-shell vial assay is a rapid alternative technique in comparison to the time consuming conventional tube cultures for the isolation of HSV-1, especially from corneal scrapings for the laboratory diagnosis of herpes simplex keratitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11882256&dopt=Abstract herpes medicine



herpes
Herpes zoster and the stage and prognosis of HIV-1 infection.

McNulty A, Li Y, Radtke U, Kaldor J, Rohrsheim R, Cooper DA, Donovan B.

Taylor Square Private Clinic, Australia.

OBJECTIVES: To examine the incidence of herpes zoster in HIV-1 infection. To assess the prognostic significance of the occurrence of herpes zoster and progression to AIDS or death DESIGN AND METHODS: 146 homosexually active men with known times of HIV-1 seroconversion were identified through the Sydney AIDS Prospective Study and the clinic records of a private medical practice with large caseload of HIV infected homosexual men. Medical records were reviewed for a history of herpes zoster, CD4+ lymphocyte counts, and HIV-1 disease status. Cox's proportional hazards model was used to determine whether herpes zoster predicted progression to AIDS or death. RESULTS: After a mean follow up of 54 months, 30 men (20%) had an episode of herpes zoster and three of these men had one recurrence. The overall incidence of herpes zoster was 44.4 episodes per 1000 person years (95% CI 30.0-63.5). Herpes zoster was not found to be a marker of deteriorating immune functions as measured by CD4+ lymphocyte counts. CD4+ counts did not differ significantly between those with and without zoster at 1 year (551 v 572.10(6)/1, p = 0.79), 2 years (451 v 557, p = 0.11), and 3 years (424 v 481, p = 0.50) following HIV-1 seroconversion. There was no statistically significant difference in progression to AIDS (RR = 1.89, 95% CI 0.80-4.46, p = 0.15) or death (RR = 0.90, 95% CI 0.31-2.65, p = 0.85) from HIV-1 sero-conversion in those who did and those who did not develop herpes zoster. CONCLUSION: The incidence of herpes zoster was consistent with the findings of other studies. There was no association between the occurrence of herpes zoster and progression of HIV-1 disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9582462&dopt=Abstract herpes medicine



herpes
A comparison of PCR with virus isolation and direct antigen detection for diagnosis and typing of genital herpes.

Slomka MJ, Emery L, Munday PE, Moulsdale M, Brown DW.

Enteric and Respiratory Virus Laboratory, Central Public Health Laboratory, London, United Kingdom.

Patients attending the genitourinary medicine clinic at Watford General Hospital, UK, were examined for clinical signs of genital herpes infection. Genital swabs were taken from 194 patients (126 female, 68 male) who presented with genital ulceration or symptoms which were suggestive of genital herpes infection. Swabs from these patients were tested by three methods: (i) Detection of herpes simplex virus (HSV) antigen by direct HSV enzyme immunoassay (EIA), (ii) HSV isolation in Vero cell culture and (iii) HSV polymerase chain reaction (PCR). HSV was detected in 76 patients (39%) by EIA, in 93 (48%) by isolation in cell culture, and in 115 (59%) by PCR. Isolation by cell culture has been considered as the "gold standard" for the detection of HSV in genital lesions, but in this study HSV PCR was significantly more sensitive. Comparison of the three methods was as follows: Cell culture vs. PCR: Sensitivity 93/115 (80.9%), Specificity 79/79 (100%). HSV EIA vs. PCR: Sensitivity 75/115 (65.2%), Specificity 78/79 (98.7%). HSV EIA vs. Cell culture: Sensitivity 75/93 (80.7%), Specificity 100/101 (99%). EIA was less effective in detecting HSV among recurrent than among first episode infections, in comparison to culture or HSV PCR. This is the first comparison of HSV PCR with two other routine diagnostic methods for confirming genital herpes infection in a symptomatic population. The infecting HSV type was identified by restriction digestion of 108 HSV amplicons: HSV-1:37/108 (34%), HSV-2:71/108 (66%). In this population HSV-1 causes a significant proportion of genital herpes cases, and HSV-1 genital infection was detected in significantly more first episode infections (40.3%) than among recurrent infections (22.2%).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9598940&dopt=Abstract herpes medicine



herpes
Herpes virus-like DNA (HHV-8) in immunosuppressive therapy-related, HIV-related and classical Kaposi's sarcoma in Norwegian patients.

Jensen P, Huang YQ, Li JJ, Clausen OP, Friedman-Kien AE.

Department of Dermatology, University of Oslo, Norway.

The recently discovered human herpes virus 8 (Kaposi's sarcoma-associated herpes virus) has been implicated in the pathogenesis of Kaposi's sarcoma. Using polymerase chain reaction we detected DNA sequences of this herpes virus in 11 of 14 biopsy specimens from Kaposi's sarcoma in Norwegian patients, including the immunosuppressive therapy-related type (3 of 3), the HIV-related type (4 of 5), and the classical type (4 of 6). The results support the hypothesis of a role for human herpes virus 8 in all types of Kaposi's sarcoma independent of geographical area.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9602228&dopt=Abstract herpes medicine



herpes
Genomic organization of the canine herpes virus US region.

Haanes EJ, Tomlinson CC.

Heska Corporation, Fort Collins, CO 80525, USA. haanese heska.com

Canine herpes virus (CHV) is an alpha-herpes virus of limited pathogenicity in healthy adult dogs and infectivity of the virus appears to be largely limited to cells of canine origin. CHV's low virulence and species specificity make it an attractive candidate for a recombinant vaccine vector to protect dogs against a variety of pathogens. As part of the analysis of the CHV genome, the authors determined the complete nucleotide sequence of the CHV US region as well as portions of the flanking inverted repeats. Seven full open reading frames (ORFs) encoding proteins larger than 100 amino acids were identified within, or partially within the CHV US: cUS2, cUS3, cUS4, cUS6, cUS7, cUS8 and cUS9; which are homologs of the herpes simplex virus type-1 US2; protein kinase; gG, gD, gI, gE; and US9 genes, respectively. An eighth ORF was identified in the inverted repeat region, cIR6, a homolog of the equine herpes virus type-1 IR6 gene. The authors identified and mapped most of the major transcripts for the predicted CHV US ORFs by Northern analysis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9620207&dopt=Abstract herpes medicine



herpes
UL27.5 is a novel gamma2 gene antisense to the herpes simplex virus 1 gene encoding glycoprotein B.

Chang YE, Menotti L, Filatov F, Campadelli-Fiume G, Roizman B.

The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, Illinois 60637, USA.

An antibody made against the herpes simplex virus 1 US5 gene predicted to encode glycoprotein J was found to react strongly with two proteins, one with an apparent Mr of 23,000 and mapping in the S component and one with a herpes simplex virus protein with an apparent Mr of 43,000. The antibody also reacted with herpes simplex virus type 2 proteins forming several bands with apparent Mrs ranging from 43,000 to 50,000. Mapping studies based on intertypic recombinants, analyses of deletion mutants, and ultimately, reaction of the antibody with a chimeric protein expressed by in-frame fusion of the glutathione S-transferase gene to an open reading frame antisense to the gene encoding glycoprotein B led to the definitive identification of the new open reading frame, designated UL27.5. Sequence analyses indicate the conservation of a short amino acid sequence common to US5 and UL27.5. The coding sequence of the herpes simplex virus UL27.5 open reading frame is strongly homologous to the sequence encoding the carboxyl terminus of the herpes simplex virus 2 UL27.5 sequence. However, both open reading frames could encode proteins predicted to be significantly larger than the mature UL27.5 proteins accumulating in the infected cells, indicating that these are either processed posttranslationally or synthesized from alternate, nonmethionine-initiating codons. The UL27.5 gene expression is blocked by phosphonoacetate, indicating that it is a gamma2 gene. The product accumulated predominantly in the cytoplasm. UL27.5 is the third open reading frame found to map totally antisense to another gene and suggests that additional genes mapping antisense to known genes may exist.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9621069&dopt=Abstract herpes medicine