herpes
3-Hydroxyphthaloyl beta-lactoglobulin. III. Antiviral activity against herpes viruses.

Neurath AR, Strick N, Li YY.

Lindsley F Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA.

The spread of sexually transmitted diseases, including human immunodeficiency virus type 1 (HIV-1) and herpes virus infections, has continued unabated despite educational efforts spearheaded as a response to the HIV-1 epidemic. This suggests the need for prophylactic measures, including the application of topical antiviral agents. Chemical modification of bovine beta-lactoglobulin (beta-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor (designated 3HP-beta-LG) shown to also have activity against herpes simplex virus types 1 and 2 (HSV-1, HSV-2). This report provides more detailed results concerning the anti-herpes virus activity of 3HP-beta-LG, indicating that this compound: (i) inhibited infection by human cytomegalovirus (HCMV), which is known to be sexually transmitted; (ii) inactivated the infectivity of both HSV-1 and HSV-2; (iii) inhibited cell-to-cell transmission of HSV-1 and HSV-2; and (iv) bound to HSV-1, HSV-2 and HCMV virus particles and partially inhibited the binding of anti-glycoprotein E (gE) and anti-gC monoclonal antibodies to HSV-1 and HSV-2. The binding of 3HP-beta-LG to the herpes viruses under study was inhibited by aggregated human IgG, suggesting that the respective viral Fc receptor is one of the target sites for 3HP-beta-LG. In agreement with results on inhibition of HIV-1 infection, 3HP-beta-LG appears to be the acid anhydride-modified protein of choice as an antiviral agent against herpes viruses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9875389&dopt=Abstract herpes medicine



herpes
Protection against herpes B virus infection in rabbits with a recombinant vaccinia virus expressing glycoprotein D.

Bennett AM, Slomka MJ, Brown DW, Lloyd G, Mackett M.

DERA, CBD Porton Down, Salisbury, United Kingdom.

Herpes B virus infects naturally monkeys of the macaque genus in whom it can cause recurrent oral and genital lesions. However, when the virus infects humans it causes a neurological illness with a high case fatality rate. Successful treatment is possible but this depends on diagnosis prior to the onset of respiratory arrest, and fatalities over the last 10 years have been the result of late or no diagnostic data on which to base anti-viral intervention. An effective vaccine would be an ideal way to combat the risk of herpes B virus disease in humans working with potentially infected monkeys or their tissues. A recombinant vaccinia virus expressing herpes B virus glycoprotein D (gD) was constructed and rabbits inoculated with the chimeric virus were tested for immunoglobulin responses to herpes B virus by virus neutralisation, ELISA and Western blot analyses. Anti-gD humoral responses were detected in all vaccinated animals by ELISA and Western blot but neutralising antibody was not detected prior to challenge with herpes B virus. Non-vaccinated rabbits died within 8 days of challenge while 10/11 vaccinated animals were protected against herpes B virus disease. No antibodies to herpes B virus proteins other than gD were detectable in surviving animals, suggesting minimal herpes B virus replication post challenge. Autopsies were carried out on 4/10 rabbits which had remained healthy at 31 days post challenge and the dorsal root ganglia adjacent to the inoculation site were removed. Attempts to detect herpes B virus DNA by PCR followed by hybridisation proved negative suggesting protection against latent herpes B virus infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9890421&dopt=Abstract herpes medicine



herpes
Viral diagnosis of neurological infection by RT multiplex PCR: a search for entero- and herpes viruses in a prospective study.

Casas I, Pozo F, Trallero G, Echevarria JM, Tenorio A.

Service of Diagnostic Microbiology, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. icasas isciii.es

The diagnosis of a wide range of different neurological syndromes was established by a reverse transcription multiplex PCR assay. The presence of enterovirus and herpes viruses was studied in cerebrospinal fluid samples collected prospectively from 200 patients hospitalized with neurological diseases suspected of viral infection. Positive PCR results for enterovirus and neurotropic herpes virus (herpes simplex, HSV, and varicella zoster, VZV) were obtained among the immunocompetent patients (55/156, 35%) who presented aseptic meningitis or encephalitis. Among immunocompromised patients the yield of positive PCR results was 41% (18/44), predominantly lymphotropic herpes viruses (15/44, 34%). Cytomegalovirus (CMV) DNA was detected in patients with several clinical syndromes, including encephalitis, chronic meningitis, retinitis, ventriculitis, polyradiculomyelitis, and myeloradiculitis. Epstein-Barr (EBV) and VZV-specific DNA sequences were detected in patients with either encephalitis, aseptic meningitis, and chronic meningitis. Dual infections of CMV and HSV or CMV and EBV were established in two AIDS patients with encephalitis and polyradiculomyelitis, respectively. The applications of this RT multiplex PCR assay are extensive and may prove to be particularly valuable for the rapid and sensitive diagnosis of neurological diseases in both immunocompetent and immunocompromised patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9892399&dopt=Abstract herpes medicine



herpes
Detection of herpes simplex virus DNA in semen of men with genital HSV-2 infection.

Wald A, Matson P, Ryncarz A, Corey L.

Department of Medicine, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, USA.

BACKGROUND AND OBJECTIVES: Previous studies, using viral culture, have suggested that herpes simplex virus (HSV) isolation from semen is rare. This study attempts to investigate further the role of semen in sexual transmission of HSV. GOALS OF THIS STUDY: To evaluate semen samples for HSV DNA with a sensitive polymerase chain reaction (PCR) test. STUDY DESIGN: Laboratory examination of 255 stored semen samples collected from 15 healthy men with genital HSV-2 infection during a prospective clinical trial. RESULTS: Herpes simplex virus DNA was detected in 8 (3.1%) semen samples, 6 of which were collected during a herpes recurrence. Herpes simplex virus DNA was not detected in any of the 18 samples collected during acyclovir therapy. CONCLUSION: Herpes simplex DNA can be detected in semen, although it appears closely associated with clinical HSV reactivation. More detailed studies will be needed to assess the role HSV-2 in semen plays in transmission of infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9918316&dopt=Abstract herpes medicine



herpes
Chronic Fatigue Syndrome and Herpesviruses: the Fading Evidence.

Soto NE, Straus SE.

National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.

Herpesviruses, in particular Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpes virus 6 (HHV-6), have, for the past two decades, come under considerable scrutiny as aetiological agents of chronic fatigue syndrome (CFS). However, virological findings of herpes viruses in CFS have not been consistent between different studies, and the unusual patterns of serological responses to EBV, CMV and HHV-6 have not been specific for CFS, being observed also in asymptomatic individuals. In addition, patients with symptomatology suggestive of CFS do not appear to have an increased frequency of these herpes viruses, as detected by culture or polymerase chain reaction, compared with controls, which argues against an ongoing active herpetic infection. Studies have also shown that the presumable elevation of antibody titres to EBV, CMV or HHV-6 in CFS are not observed only with these viruses, but also with other organisms such as herpes simplex virus and measles.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11867001&dopt=Abstract herpes medicine



herpes
The prevalence of herpes family virus DNA in the conjunctiva of patients positive and negative for human immunodeficiency virus using the polymerase chain reaction.

Lee-Wing MW, Hodge WG, Diaz-Mitoma F.

University of Ottawa Eye Institute, Ontario, Canada.

OBJECTIVE: To help understand the pathogenesis of herpes family virus ocular infection among patients positive for HIV, the authors compared the rates of detection of herpes family virus DNA from the conjunctiva of patients who are positive and negative for human immunodeficiency virus (HIV) using the polymerase chain reaction (PCR). DESIGN: Cross-sectional study. PARTICIPANTS: The conjunctival scrapings of 30 patients positive for HIV and 30 patients negative for HIV were examined. INTERVENTION: PCR was used to assay for the presence of herpes simplex virus type 1 (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA (n = 240 samples). MAIN OUTCOME MEASURE: The rate of detection of virus DNA in the two groups, controlling for age, gender, and race, was measured. RESULTS: HSV and VZV DNA were not detected in any of the HIV-positive or HIV-negative samples. CMV DNA was detected in 20% (6 of 30) of patients positive for HIV and was undetected in control subjects negative for HIV (P = 0.01). EBV DNA was detected in 40% (12 of 30) of patients positive for HIV and in 47% (14 of 30) of control subjects negative for HIV (P = 0.58). CONCLUSIONS: There was no difference in the frequency of detection of HSV, VZV, or EBV DNA from the conjunctiva of patients positive or negative for HIV. Only CMV DNA was detected at a significantly higher rate in the conjunctiva of patients positive for HIV compared with control subjects negative for HIV. These different rates of peripheral virus shedding may be one possible explanation for the different rates of clinical infection among the herpes family viruses among patients positive for HIV.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9951489&dopt=Abstract herpes medicine



herpes
Regulated expression of a Sindbis virus replicon by herpes virus promoters.

Ivanova L, Schlesinger S, Olivo PD.

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.

We describe the use of herpes virus promoters to regulate the expression of a Sindbis virus replicon (SINrep/LacZ). We isolated cell lines that contain the cDNA of SINrep/LacZ under the control of a promoter from a herpes virus early gene which requires regulatory proteins encoded by immediate-early genes for expression. Wild-type Sindbis virus and replicons derived from this virus cause death of most vertebrate cells, but the cells discussed here grew normally and expressed the replicon and beta-galactosidase only after infection with a herpes virus. Vero cell lines in which the expression of SINrep/LacZ was regulated by the herpes simplex virus type 1 (HSV-1) infected-cell protein 8 promoter were generated. One Vero cell line (V3-45N) contained, in addition to the SINrep/LacZ cDNA, a Sindbis virus-defective helper cDNA which provides the structural proteins for packaging the replicon. Infection of V3-45N cells with HSV-1 resulted in the production of packaged SINrep/LacZ replicons. HSV-1 induction of the Sindbis virus replicon and packaging and spread of the replicon led to enhanced expression of the reporter gene, suggesting that this type of cell could be used to develop sensitive assays to detect herpes viruses. We also isolated a mink lung cell line that was transformed with SINrep/LacZ cDNA under the control of the promoter from the human cytomegalovirus (HCMV) early gene UL45. HCMV carries out an abortive infection in mink lung cells, but it was able to induce the SINrep/LacZ replicon. These results, and those obtained with an HSV-1 mutant, demonstrate that this type of signal amplification system could be valuable for detecting herpes viruses for which a permissive cell culture system is not available.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9971780&dopt=Abstract herpes medicine



herpes
Capsid structure of simian cytomegalovirus from cryoelectron microscopy: evidence for tegument attachment sites.

Trus BL, Gibson W, Cheng N, Steven AC.

Laboratory of Structural Biology, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA.

We have used cryoelectron microscopy and image reconstruction to study B-capsids recovered from both the nuclear and the cytoplasmic fractions of cells infected with simian cytomegalovirus (SCMV). SCMV, a representative betaherpes virus, could thus be compared with the previously described B-capsids of the alphaherpes viruses, herpes simplex virus type 1 (HSV-1) and equine herpes virus 1 (EHV-1), and of channel catfish virus, an evolutionarily remote herpes virus. Nuclear B-capsid architecture is generally conserved with SCMV, but it is 4% larger in inner radius than HSV-1, implying that its approximately 30% larger genome should be packed more tightly. Isolated SCMV B-capsids retain a relatively well preserved inner shell (or "small core") of scaffolding-assembly protein, whose radial-density profile indicates that this protein is approximately 16-nm long and consists of two domains connected by a low-density linker. As with HSV-1, the hexons but not the pentons of the major capsid protein (151 kDa) bind the smallest capsid protein (approximately 8 kDa). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed cytoplasmic B-capsid preparations to contain proteins similar in molecular weight to the basic phosphoprotein (approximately 119 kDa) and the matrix proteins (65 to 70 kDa). Micrographs revealed that these particles had variable amounts of surface-adherent material not present on nuclear B-capsids that we take to be tegument proteins. Cytoplasmic B-capsids were classified accordingly as lightly, moderately, or heavily tegumented. By comparing the three corresponding density maps with each other and with the nuclear B-capsid, two interactions were identified between putative tegument proteins and the capsid surface. One is between the major capsid protein and a protein estimated by electron microscopy to be 50 to 60 kDa; the other involves an elongated molecule estimated to be 100 to 120 kDa that is anchored on the triplexes, most likely on its dimer subunits. Candidates for the proteins bound at these sites are discussed. This first visualization of such linkages makes a step towards understanding the organization and functional rationale of the herpes virus tegument.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9971801&dopt=Abstract herpes medicine