herpes
Detection of cervical infections in colposcopy clinic patients.

Lanham S, Herbert A, Basarab A, Watt P.

Department of Molecular Microbiology, Southampton General Hospital, Southampton SO16 6YD, United Kingdom. sal3 soton.ac.uk

The purpose of this study was to determine if Neisseria gonorrhoeae; Chlamydia trachomatis; herpes simplex virus; cytomegalovirus; Epstein-Barr virus; human herpes viruses 6, 7, and 8; or adeno-associated virus influenced the production of cervical intraepithelial neoplasia. Two hundred thirty-one cervical smear samples were tested for the presence of the organisms by PCR. In addition, human papillomavirus types in the samples were determined by PCR and classified into cancer risk types of high, moderate, and low. There was no link with cervical intraepithelial neoplasia status and detection of herpes simplex virus, cytomegalovirus, Epstein-Barr virus, human herpes viruses 6 and 8, gonorrhea, or chlamydia. However, high-grade cervical intraepithelial neoplasia was found more frequently with mixed infection by moderate-risk human papillomavirus types and human herpes virus 7 than with these papillomavirus types alone. The presence of human herpes virus 7 may increase the oncogenic potential of moderate-risk human papillomavirus types.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11474018&dopt=Abstract herpes medicine



herpes
Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients.

Conejero-Goldberg C, Torrey EF, Yolken RH.

Stanley Brain Research Laboratory, Department of Psychiatry, Uniformed Services University of Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. goldbergc stanleyresearch.org

Herpes simplex virus (HSV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6) are viruses capable of establishing latency. All of these infect the CNS and have been detected in human postmortem brains. Toxoplasma gondii is a protozoan organism which can reactivate in the brains of previously infected immunocompromised individuals. To screen for the presence of herpes viruses and T. gondii in postmortem orbital frontal brain samples from patients with schizophrenia, affective disorders, and controls, we used nested-polymerase chain reaction (n-PCR)/sequencing. We identified HHV-6B sequences in 2/51 postmortem brain samples but no sequences from other herpes viruses. We did not detect sequences of T. gondii in the postmortem brains. Additional studies including ones directed at the sensitive detection of viral nucleic acids in multiple brain regions should be directed at confirming or excluding a role for viruses and protozoa in the etiology of these disorders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12505139&dopt=Abstract herpes medicine



herpes
Herpes simplex virus type 2 infection as a risk factor for human immunodeficiency virus acquisition in men who have sex with men.

Renzi C, Douglas JM Jr, Foster M, Critchlow CW, Ashley-Morrow R, Buchbinder SP, Koblin BA, McKirnan DJ, Mayer KH, Celum CL.

Department of Medicine, University of Washington, Seattle, USA.

The association of human immunodeficiency virus (HIV) acquisition with herpes simplex virus type 2 (HSV-2) was assessed among men who have sex with men (MSM) in a nested case-control study of 116 case subjects who seroconverted to HIV during follow-up and 342 control subjects who remained HIV seronegative, frequency-matched by follow-up duration and report of HIV-infected sex partner and unprotected anal sex. The baseline HSV-2 seroprevalence was higher among case (46%) than control (34%) subjects (P=.03); the HSV-2 seroincidence was 7% versus 4% (P=.3). Only 15% of HSV-2-infected MSM reported herpes outbreaks in the past year. HIV acquisition was associated with prior HSV-2 infection (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.9), reporting >12 sex partners (OR, 2.9; 95% CI, 1.4-6.3), and reporting fewer herpes outbreaks in the past year (OR, 0.3; 95% CI, 0.1-0.8). HSV-2 increases the risk of HIV acquisition, independent of recognized herpes lesions and behaviors reflecting potential HIV exposure. HSV-2 suppression with antiviral therapy should be evaluated as an HIV prevention strategy among MSM.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12508142&dopt=Abstract herpes medicine



herpes
Acyclovir-resistant genital herpes among persons attending sexually transmitted disease and human immunodeficiency virus clinics.

Reyes M, Shaik NS, Graber JM, Nisenbaum R, Wetherall NT, Fukuda K, Reeves WC; Task Force on Herpes Simplex Virus Resistance.

Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

BACKGROUND: Genital herpes is epidemic in the United States; long-term acyclovir therapy is common; and long-term use of antimicrobials in suppressive doses favors development of resistance. OBJECTIVE: To determine the prevalence of and risk factors for acyclovir-resistant genital herpes. METHODS: We identified and attempted to enroll all patients 18 years or older with suspected genital herpes who attended 22 sexually transmitted disease and human immunodeficiency virus (HIV) clinics in the United States between October 1996 and April 1998. We conducted standardized interviews of all consenting patients. Lesions were cultured, and isolates were typed as herpes simplex virus (HSV) 1 or HSV-2 and tested for acyclovir sensitivity (using a 50% inhibitory concentration of 2 microg/mL) by plaque reduction, which was independently confirmed. RESULTS: Herpes simplex virus was isolated from 2088 of 3602 patients, and 90.2% of isolates were HSV-2. Fifteen isolates, all HSV-2, were acyclovir resistant. Three (0.18%) of 1644 HIV-negative patients had acyclovir-resistant isolates (95% confidence interval [CI], 0.04%-0.5%); resistance was associated with oral (P<.006) and topical (P<.001) acyclovir use. Twelve (5.3%) of 226 HIV-positive patients yielded resistant HSV isolates (95% CI, 2.8%-9.1%); resistance was associated with oral acyclovir use (P<.001), duration of the current episode (P<.001), history of recurrent genital herpes (P<.01), and low CD4 cell count (P<.05). CONCLUSIONS: In the 15 years following licensure of acyclovir, resistance to the drug remains low among immunocompetent patients. However, 5% of HIV-positive patients had resistant HSV-2 isolates. Continued surveillance is essential to monitor changes in acyclovir resistance and to characterize the clinical and public health importance of acyclovir-resistant HSV.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12523920&dopt=Abstract herpes medicine



herpes
Therapeutic Options for Herpes Simplex Infections.

Au E, Sacks SL.

Department of Pharmacology and Therapeutics, The University of British Columbia, Viridae Clinical Sciences Inc.,1134 Burrard Street, Vancouver, BC, Canada V6Z 1Y8. sacks viridae.com

Herpes simplex viruses are responsible for a number of disease states in infected individuals. Capable of establishing latent infection, herpes simplex can reactivate, causing pain, discomfort, and psychosocial consequences. Because no cure is available, treatment modalities for herpes simplex infection are required, from both personal and public health standpoints. To date, therapy has centered around the use of antiviral drugs to control infection and suppress recurrences. To expand the scope of available treatments, efforts have focused on the development of vaccines against herpes simplex virus and new agents such as immune response modifiers. Recent data suggest that these new agents are promising in their therapeutic potential.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12525287&dopt=Abstract herpes medicine



herpes
Amino acid changes within conserved region III of the herpes simplex virus and human cytomegalovirus DNA polymerases confer resistance to 4-oxo-dihydroquinolines, a novel class of herpes virus antiviral agents.

Thomsen DR, Oien NL, Hopkins TA, Knechtel ML, Brideau RJ, Wathen MW, Homa FL.

Infectious Disease Biology, Pharmacia Corporation, Kalamazoo, Michigan 49001, USA.

The 4-oxo-dihydroquinolines (PNU-182171 and PNU-183792) are nonnucleoside inhibitors of herpes virus polymerases (R. J. Brideau et al., Antiviral Res. 54:19-28, 2002; N. L. Oien et al., Antimicrob. Agents Chemother. 46:724-730, 2002). In cell culture these compounds inhibit herpes simplex virus type 1 (HSV-1), HSV-2, human cytomegalovirus (HCMV), varicella-zoster virus (VZV), and human herpes virus 8 (HHV-8) replication. HSV-1 and HSV-2 mutants resistant to these drugs were isolated and the resistance mutation was mapped to the DNA polymerase gene. Drug resistance correlated with a point mutation in conserved domain III that resulted in a V823A change in the HSV-1 or the equivalent amino acid in the HSV-2 DNA polymerase. Resistance of HCMV was also found to correlate with amino acid changes in conserved domain III (V823A+V824L). V823 is conserved in the DNA polymerases of six (HSV-1, HSV-2, HCMV, VZV, Epstein-Barr virus, and HHV-8) of the eight human herpes viruses; the HHV-6 and HHV-7 polymerases contain an alanine at this amino acid. In vitro polymerase assays demonstrated that HSV-1, HSV-2, HCMV, VZV, and HHV-8 polymerases were inhibited by PNU-183792, whereas the HHV-6 polymerase was not. Changing this amino acid from valine to alanine in the HSV-1, HCMV, and HHV-8 polymerases alters the polymerase activity so that it is less sensitive to drug inhibition. In contrast, changing the equivalent amino acid in the HHV-6 polymerase from alanine to valine alters polymerase activity so that PNU-183792 inhibits this enzyme. The HSV-1, HSV-2, and HCMV drug-resistant mutants were not altered in their susceptibilities to nucleoside analogs; in fact, some of the mutants were hypersensitive to several of the drugs. These results support a mechanism where PNU-183792 inhibits herpes viruses by interacting with a binding determinant on the viral DNA polymerase that is less important for the binding of nucleoside analogs and deoxynucleoside triphosphates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12525621&dopt=Abstract herpes medicine



herpes
[Study on the anti-herpes simplex virus activity of a suppository or ointment form of Astragalus membranaceus combined with interferon alpha 2b in human diploid cell culture]

[Article in Chinese]

Zhang L, Liu Y, Yu Z.

Biotech Center for New Pharmaceutical Development, Chinese Academy of Preventive Medicine, State Key Laboratory for Molecular Virology and Genetic Engineering, Beijing 100052.

A study on the anti-herpes simplex virus activity of the suppository or ointment form of Astragalus membranaceus(AM) combined with recombinant human interferon alpha 2b(IFN) was carried out in human diploid cell culture. AM is a Chinese herb medicine and have been used in China as a tonic for thousands of years and the IFN was produced from E. coli with 95% purity. Obtained results indicated that the placebo suppository and ointment(without AM and IFN) seemed not to decrease markedly the anti-viral activity of IFN in WISH/VSV assay system. The anti-herpes simplex virus activities of suppository and ointment forms of AM and IFN were shown to be significantly higher than that of IFN alone. It is well known that chronic cervicitis is closely related to papillomavirus, cytomegalovirus as well as herpes virus infections. The AM-IFN suppository is suggested to be used in the treatment of cervicitis and the ointment in the treatment of skin herpes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12526333&dopt=Abstract herpes medicine



herpes
Herpes simplex virus type II is not a cofactor to human papillomavirus in cancer of the uterine cervix.

Tran-Thanh D, Provencher D, Koushik A, Duarte-Franco E, Kessous A, Drouin P, Wheeler CM, Dubuc-Lissoir J, Gauthier P, Allaire G, Vauclair R, Dipaolo JA, Gravitt P, Franco E, Coutlee F.

Departements de Microbiologie-Infectiologie, Gynecologie-Obstetrique et de Pathologie, Centre Hospitalier de l'Universite de Montreal, Universite de Montreal, Montreal, Quebec, Canada.

OBJECTIVE: Cells that were cotransfected with herpes simplex virus-16 and the herpes simplex virus type 2 Xho -2 DNA induce tumors in nude mice. In a cross-sectional study, we investigated the role of herpes simplex virus type 2 as a cofactor to human papillomavirus in cervical cancer. STUDY DESIGN: Cervical cells that were obtained with an endocervical Cytobrush brush (Medscand) from 439 women (50 women with cancer lesions, 65 women with high-grade squamous intraepithelial lesions, 80 women with low-grade squamous intraepithelial lesions, 244 healthy subjects) and DNA that was extracted from 150 cervical cancer biopsy specimens were analyzed with polymerase chain reaction for herpes simplex virus type 2 Xho -2 and Bgl IIC transforming DNA sequences. RESULTS: All 439 cervical samples and 150 cervical cancer biopsy specimens tested negative for herpes simplex virus type 2 Xho -2 and Bgl IIC DNA by polymerase chain reaction. Overall, none of 200 samples (0%) from women with invasive cervical cancer contained herpes simplex virus type 2 Xho -2 or Bgl IIC DNA (95% CI, 0.0-1.8). CONCLUSION: Although herpes simplex virus type 2 Bgl IIN transforms epithelial cells in vitro, it was not detected in cervical cancer specimens.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12548206&dopt=Abstract herpes medicine



herpes
Conserved protein kinases encoded by herpes viruses and cellular protein kinase cdc2 target the same phosphorylation site in eukaryotic elongation factor 1delta.

Kawaguchi Y, Kato K, Tanaka M, Kanamori M, Nishiyama Y, Yamanashi Y.

Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan. ykawagu med.nagoya-u.ac.jp

Earlier studies have shown that translation elongation factor 1delta (EF-1delta) is hyperphosphorylated in various mammalian cells infected with representative alpha-, beta-, and gammaherpes viruses and that the modification is mediated by conserved viral protein kinases encoded by herpes viruses, including UL13 of herpes simplex virus type 1 (HSV-1), UL97 of human cytomegalovirus, and BGLF4 of Epstein-Barr virus (EBV). In the present study, we attempted to identify the site in EF-1delta associated with the hyperphosphorylation by the herpes virus protein kinases. Our results are as follows: (i) not only in infected cells but also in uninfected cells, replacement of the serine residue at position 133 (Ser-133) of EF-1delta by alanine precluded the posttranslational processing of EF-1delta, which corresponds to the hyperphosphorylation. (ii) A purified chimeric protein consisting of maltose binding protein (MBP) fused to a domain of EF-1delta containing Ser-133 (MBP-EFWt) is specifically phosphorylated in in vitro kinase assays by purified recombinant UL13 fused to glutathione S-transferase (GST) expressed in the baculovirus system. In contrast, the level of phosphorylation by the recombinant UL13 of MBP-EFWt carrying an alanine replacement of Ser-133 (MBP-EFS133A) was greatly impaired. (iii) MBP-EFWt is also specifically phosphorylated in vitro by purified recombinant BGLF4 fused to GST expressed in the baculovirus system, and the level of phosphorylation of MBP-EFS133A by the recombinant BGLF4 was greatly reduced. (iv) The sequence flanking Ser-133 of EF-1delta completely matches the consensus phosphorylation site for a cellular protein kinase, cdc2, and in vitro kinase assays revealed that purified cdc2 phosphorylates Ser-133 of EF-1delta. (v) As observed with EF-1delta, the casein kinase II beta subunit (CKIIbeta) was specifically phosphorylated by UL13 in vitro, while the level of phosphorylation of CKIIbeta by UL13 was greatly diminished when a serine residue at position 209, which has been reported to be phosphorylated by cdc2, was replaced with alanine. These results indicate that the conserved protein kinases encoded by herpes viruses and a cellular protein kinase, cdc2, have the ability to target the same amino acid residues for phosphorylation. Our results raise the possibility that the viral protein kinases mimic cdc2 in infected cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12551973&dopt=Abstract herpes medicine