Efficacy of transfer factor in treating patients with recurrent ocular herpes infections

Recurrent ocular herpes is an insoluble problem for the clinician. As cellular immunity plays an important role in controlling herpes relapses, and other studies have shown the efficacy of HSV-specific transfer factor (TF) for the treatment of herpes patients, an open clinical trial was undertaken in 134 patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from recurrent ocular herpetic infections. The mean duration of the treatment was 358 days, and the entire follow-up period 189121 before, and 64062 days after TF treatment. The cell-mediated immune response to the viral antigens, evaluated by the lymphocyte stimulation test (LST) and the leucocyte migration test (LMT) (P<0.001), was significantly increased by the TF treatment. The total number of relapses was decreased significantly during/after TF treatment, dropping from 832 before, to 89 after treatment, whereas the cumulative relapse index (RI) dropped, during the same period, from 13.2 to 4.17 (P<0.0001). No side effects were observed. It is concluded that patients with relapsing ocular herpes can benefit from treatment with HSV-specific TF.     

Ocular herpes:the pathophysiology,management and treatment of herpetic eye diseases

Herpesviruses are a prominent cause of human viral disease, second only to the cold and influenza viruses. Most herpesvirus infections are mild or asymptomatic. However, when the virus invades the eye, a number of pathologies can develop and its associated sequelae have become a considerable source of ocular morbidity. The most common culprits of herpetic eye disease are the herpes simplex virus(HSV), varicella zoster virus(VZV), and cytomegalovirus(CMV). While primary infection can produce ocular disease, the most destructive manifestations tend to arise from recurrent infection. These recurrent infections can wreck devastating effects and lead to irreversible vision loss accompanied by a decreased quality of life, increased healthcare usage, and significant cost burden. Unfortunately, no method currently exists to eradicate herpesviruses from the body after infection. Treatment and management of herpes-related eye conditions continue to revolve around antiviral drugs, although corticosteroids, interferons, and other newer therapies may also be appropriate depending on the disease presentation. Ultimately, the advent of effective vaccines will be crucial to preventing herpesvirus diseases altogether and cutting the incidence of ocular complications.     

Ocular herpes: the pathophysiology,management and treatment of herpetic eye diseases

Herpesviruses are a prominent cause of human viral disease, second only to the cold and influenza viruses. Most herpesvirus infections are mild or asymptomatic. However, when the virus invades the eye, a number of pathologies can develop and its associated sequelae have become a considerable source of ocular morbidity. The most common culprits of herpetic eye disease are the herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV). While primary infection can produce ocular disease, the most destructive manifestations tend to arise from recurrent infection. These recurrent infections can wreck devastating effects and lead to irreversible vision loss accompanied by a decreased quality of life, increased healthcare usage, and significant cost burden. Unfortunately, no method currently exists to eradicate herpesviruses from the body after infection. Treatment and management of herpes-related eye conditions continue to revolve around antiviral drugs, although corticosteroids, interferons, and other newer therapies may also be appropriate depending on the disease presentation. Ultimately, the advent of effective vaccines will be crucial to preventing herpesvirus diseases altogether and cutting the incidence of ocular complications.     

Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro

The virucidal effect of peppermint oil, the essential oil of Mentha piperita, against herpes simplex virus was examined. The inhibitory activity against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) was tested in vitro on RC-37 cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of peppermint oil for herpes simplex virus plaque formation was determined at 0.002% and 0.0008% for HSV-1 and HSV-2, respectively. Peppermint oil exhibited high levels of virucidal activity against HSV-1 and HSV-2 in viral suspension tests. At noncytotoxic concentrations of the oil, plaque formation was significantly reduced by 82% and 92% for HSV-1 and HSV-2, respectively. Higher concentrations of peppermint oil reduced viral titers of both herpesviruses by more than 90%. A clearly time-dependent activity could be demonstrated, after 3 h of incubation of herpes simplex virus with peppermint oil an antiviral activity of about 99% could be demonstrated. In order to determine the mode of antiviral action of the essential oil, peppermint oil was added at different times to the cells or viruses during infection. Both herpesviruses were significantly inhibited when herpes simplex virus was pretreated with the essential oil prior to adsorption. These results indicate that peppermint oil affected the virus before adsorption, but not after penetration into the host cell. Thus this essential oil is capable to exert a direct virucidal effect on HSV. Peppermint oil is also active against an acyclovir resistant strain of HSV-1 (HSV-1-ACV(res)), plaque formation was significantly reduced by 99%. Considering the lipophilic nature of the oil which enables it to penetrate the skin, peppermint oil might be suitable for topical therapeutic use as virucidal agent in recurrent herpes infection.     

Transfer factor prevents relapses in herpes keratitis patients: A pilot study

Transfer Factor is a dialysable moiety obtained from immune lymphocytes. It has been successfully used for the treatment of several viral infections including labial and genital herpes. In the present study, thirty-three patients with low immune response to HSV antigens and suffering from herpes ocular infections were orally treated with HSV-specific transfer factor (TF). Their relapse index was reduced from 20.1 before treatment to 0.51 after TF administration, with only 6/33 patients relapsing. Although this is not a placebo-controlled-randomized study, the results suggest that TF specific for HSV antigens may be efficacious for preventing relapses of ocular herpes infections as has been the case with genital and labial localisations.Abbreviations CMI Cell-mediated immunity - CMV Cytomegalo-virus - EBV Epstein-Barr virus - HIV Human immunodeficiency virus - HK Herpes keratitis - HSV Herpes simplex virus - IRI Individual relapse index - KU Kerato-uveitis - LMT Leucocyte migration test - LST Lymphocyte stimulation test - MIF Migration inhibition factor - RHK Relapsing herpes keratitis - TF Transfer factor     

Direct lymphocytotoxicity against herpes simplex virus infected cells.

This study was undertaken to determine if direct cytotoxicity (DC) against herpes simplex virus infected cells, perhaps mediated by T cells, could be demonstrated in individuals subject to recurrent herpes labialis. The mononuclear cells from 7 out of 17 individuals with recurrent herpes expressed DC whereas no DC was ever exhibited by 7 individuals without a previous history of herpes infections. Several approaches were used to show that the cytotoxicity being detected was predominately of the direct type rather than antibody-dependent cell cytotoxicity (ADCC). Since the effector cells of the DC were sensitive to trypsin treatment and behaved as do natural killer (NK) cells upon cell fractionation, the results were taken to imply that the DC was attributable to a NK-effector cell type rather than a classical T lymphocyte.     

Proteomics in immunity and herpes simplex encephalitis

The genetic theory of infectious diseases has proposed that susceptibility to life-threatening infectious diseases in childhood, occurring in the course of primary infection, results mostly from individually rare but collectively diverse single-gene variants. Recent evidence of an ever-expanding spectrum of genes involved in susceptibility to infectious disease indicates that the paradigm has important implications for diagnosis and treatment. One such pathology is childhood herpes simplex encephalitis, which shows a pattern of rare but diverse disease-disposing genetic variants. The present report shows how proteomics can help to understand susceptibility to childhood herpes simplex encephalitis and other viral infections, suggests that proteomics may have a particularly important role to play, emphasizes that variation over the population is a critical issue for proteomics and notes some new challenges for proteomics and related bioinformatics tools in the context of rare but diverse genetic defects.     

Identification and analysis of putative promoter motifs in bovine herpes virus

The purpose of this study is to identify and analyse the putative promoter motifs in the bovine herpes virus which causes several diseases in cattle worldwide including bovine mastitis with large economic impact on dairy industry. Bovine mastitis caused due to virus is often neglected as bacterial infections are held mainly responsible for the disease. Therefore, in this in silico investigation with all the existing experimental data a total of 147 promoter were identified along with their sequences from three genome viz bovine herpes virus 1 (BHV), bovine herpes virus 4 and bovine herpes virus 5, out of which 39 promoters were from bovine herpes virus 4 (BHV 4), 95 from BHV1 and 13 from BHV5 and it was observed that BHV1 and BHV5 have a close evolutionary history. However, they belong to the same subfamily and size of the genome and GC% of BHV1 and BHV5 was almost equal and very high compare to that of BHV4. This analysis may help in designing the live attenuated vaccine against BHV causing bovine mastitis that reduces the incidence of bovine mastitis. Identification of promoters may also help in designing of expression vectors which help in better understanding of the regulation of gene expression. In the era of large genomics and proteomics prediction of promoters in the whole genome is crucial for the advancement of drug discovery and gene therapy.     

细胞培养、酶联免疫法检测生殖器疱疹病毒的对比性研究

目的分析酶联免疫法（EIA）在检测生殖器疱疹病毒的可行性。方法收集性病门诊患者标本338例进行细胞培养和EIA法检测,另将两法检测结果不相符的标本采用荧光PCR复检,比较分析细胞培养、EIA法与扩大金标准结果的相符性。结果分析表明细胞培养与EIA法检测生殖器疱疹病毒的敏感性均为90．24％,特异性分别为100％和96．29％。结论EIA法检测生殖器疱疹病毒有较高的敏感性而且方法简便、快速,可以用于大批量标本的检测和流行病学的筛查。     

Evidence for a protein(s) bound to herpes simples virus DNA.

The $\text{Xba}$ I cleavage pattern of highly purified, but not specifically deproteinized, herpes simplex virus DNA does not match published patterns. If the purified herpes simplex virus DNA is first extracted with phenol and then digested with $\text{Xba}$ I, the cleavage pattern matches the published patterns. This comparison is taken as supportive of the hypothesis that there is a protein(s) bound to herpes simplex virus DNA.     

Prevalence of Herpes Simplex Virus Type 1- and 2- Specific Antibodies among the Acute,Recurrent, and Provoked Types of Female Genital Herpes

Sixty-eight sera from the acute, recurrent, and provoked types of female genital herpes were compared for the seroprevalence of herpes simplex virus (HSV) types 1 and 2 by immunodot assay using HSV glycoprotein G. In the HSV-1-isolated patients, no HSV-2 antibodies were detected, whereas in the HSV-2-isolated patients, HSV-1 seroprevalence was 9% for the acute type, 89% for the provoked type (P< 0.005), and 55% for the recurrent type (P<0.05). The natural history of female genital herpes and the possible protective role of pre-existing antibodies in preventing the acquisition or clinical manifestation of a subsequent HSV infection are discussed.     

Antiviral and virucidal activities against herpes simplex viruses of umesu phenolics extracted from Japanese apricot

Umesu phenolics were obtained from the salt extracts of Japanese apricot (Nanko‐mume cultivar of Prunus mume Sieb. et Zucc.) as purified phenolics. The antiviral activities of umesu phenolics obtained were then examined against herpes simplex virus type 1 (HSV‐1) and type 2 (HSV‐2), enveloped DNA viruses. The phenolics inhibited the multiplication of these viruses when added to the culture media of the infected cells. This inhibition occurred at phenolic concentrations at which they showed no severe cytotoxicity. One‐step growth experiments showed that the eclipse period in the HSV‐1 multiplication process was extended in the presence of umesu phenolics and that the addition of phenolics after the completion of viral DNA replication did not affect their multiplication. More drastic effects were observed on virucidal activities against HSV‐1 and HSV‐2; the infectivity decreased to 0.0001 when infected cells were incubated with 3 mg/ml phenolics at 30°C for 5 min. These results demonstrate the antiviral and virucidal activities of umesu phenolics and suggest a potential pharmacological use for these phenolics as a sanitizing or preventive medicine against superficial HSV infections.     

Genital herpes and personality

Genital herpes, while having gained considerable attention as an important psychosexual disease, is not well understood. Precisely what factors trigger infectious reactivation is an important question that has yet to be answered. The present study investigated the relationship between recurrent genital herpes and personality. High and low recurrers were administered a demographic and disease history questionnaire and the Minnesota Multiphasic Personality Inventory (MMPI). Results revealed that, compared to low recurrers, the mean MMPI profile of high recurrers showed significantly greater elevations on nine of ten scales. The degree and pattern of elevation in the high profile is consistent with increased levels of autonomic arousal and stress. These findings are interpreted as suggestive of the possible role of personality in influencing the rate of infectious recurrence in genital herpes sufferers. The implications for psychologically based treatment strategies are discussed.     

Cyprinid herpes virus-3 (CyHV-3) bears genes of genetically distant large DNA viruses

A large DNA virus, designated koi herpes virus (KHV), carp interstitial nephritis gill necrosis virus (CNGV) and Cyprinid herpes virus-3 (CyHV-3), causes massive mortality of carp. Morphologically, the virus resembles herpes viruses, but it contains a genome of ca 295 kbp, larger than that of any Herpesviridae member. Interestingly, three CyHV-3 genes, thymidylate monophosphate kinase (TmpK), ribonucleotide reductase and thymidine kinase, which are involved in deoxynucleotide tri-phosphate synthesis, resemble those of pox viruses. In addition to the TmpK gene, which is nonexistent in the genome of herpes viruses, CyHV-3 contains a B22R-like gene, exclusively expressed by pox viruses. These results raise questions on the phylogenic origin of CyHV-3.     

Antigen-presenting liposomes are effective in treatment of recurrent herpes simplex virus genitalis in guinea pigs.

The therapeutic and immunologic effects of a liposome preparation containing both a macrophage activator, muramyl-tripeptide-phosphatidylethanolamine, and a recombinant antigen, glycoprotein D of herpes simplex virus type 1, have been investigated. This preparation was tested in vitro for the ability to stimulate peripheral blood lymphocytes and in vivo for the control of recurrent herpes genitalis in guinea pigs. Our results show that the liposome-antigen-adjuvant preparation is capable of enhancing antigen-specific lymphocyte stimulation, which may be related to the observed 75% suppression of the frequency and severity of reactivation of recurrent herpes simplex virus type 2 genitalis compared with that of placebo controls.     

FTIR spectroscopic method for detection of cells infected with herpes viruses

Microscopic FTIR spectroscopy was used to investigate the spectral differences between normal cells in culture and cells infected with various members of the herpes family of viruses [Herpes simplex (HSV) and Varicella zoster (VZV)]. The main objective of this study is to evaluate the possibility of developing microscopic FTIR spectroscopy as a sensitive assay for the detection of herpetic infections at their early stages. The advantage of this method over conventional FTIR spectroscopy is that it facilitates inspection of restricted regions of tissue. Our results showed significant and consistent differences between all normal and HSV or VZV infected cells that were tested. Detectable and significant spectral differences between normal and infected cells are seen as early as 24 h postinfection, but the damage of the cells (cytopathic effect), caused by the infecting virus, can be seen by optical microscope observations at only 3 days postinfection. An impressive increase in the levels of vital cellular metabolites was seen in the herpes virus infected cells compared to normal cells. It seems that this spectral behavior is unique for infection with herpes viruses, because when these cells were infected with other viruses from different families like retroviruses, a considerable decrease in the levels of vital cellular metabolites was seen in infected cells compared to normal cells. Cluster analysis performed on FTIR mass chromatography yielded 100% accuracy in classifying control uninfected and VZV or HSV infected cells. Our data strongly support the possibility of developing FTIR microscopy as a diagnostic method for early detection of herpetic infections.     

Variation in the WBC differential count and other factors associated with reporting of herpes labialis: a population-based study of adults

Reactivation of latent herpes virus has been linked to triggers of mild immunosupression, such as stress or UV-exposure. Despite having predictive value in severe immunodeficiency, the white blood cell (WBC) differential count has not been examined in relation to risk of herpes reactivation in population studies. The WBC differential count and other risk factors for herpes labialis were examined in 5687 adults (ages 18-64) from the Third National Health and Nutrition Examination Survey, who had WBC 3.5-11 x 10(6) cells mL(-1) and reported no acute infections in the past month. The association between self-reported herpes labialis in the past year and the WBC differential count was modeled, adjusting for age, sex, race/ethnicity, education, smoking, upper respiratory infections (URI), and HSV-1 antibodies. Herpes labialis was significantly associated with white race/ethnicity, being a nonsmoker, and frequent URI. Compared with the highest quartile, being in the lowest quartile of granulocytes was associated with herpes labialis, adjusted odds ratio=1.82 (95% confidence interval 1.20, 2.28). At the same time, there was a trend towards an inverse association of lower lymphocyte count and herpes labialis. These findings suggest that moderate differences in the WBC differential count are related to reactivation of HSV-1. Prospective studies may help to show whether such differences indicate susceptibility to loss of latency or represent a consequence of reactivated infection.     

Successful treatment of herpes labialis with topical acyclovir.

A double blind, placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 49 patients with recurrent herpes labialis. These patients had a total of 74 episodes, 34 of which were treated with the 5% acyclovir cream and 40 with matching placebo. First episodes and all episodes treated with acyclovir cream had significantly shorter times to formation of ulcer or crust and to complete healing (p less than 0.05 for all variables). The duration of all symptoms and proportion of patients developing itching was also reduced by acyclovir cream in first episodes, though the difference was not significant. When the patient started treatment early in the course of a first episode acyclovir cream significantly reduced the percentage of lesions progressing beyond the papular stage (p less than 0.05). Acyclovir cream is well tolerated and effective for the treatment of recurrent herpes labialis.     

The role of oral acyclovir in the management of genital herpes simplex.

Oral acyclovir is an antiviral nucleoside analogue that has recently been released in Canada for use in selected patients with genital infections by the herpes simplex virus. First episodes of genital herpes should be treated with oral acyclovir as soon as the diagnosis is considered. Most people with recurrent genital herpes do not require systemic drug therapy. Selected patients with severe or long-lasting recurrences, recurrences associated with long prodromal periods (greater than 12 to 24 hours) or systemic complications such as erythema multiforme and eczema herpeticum may receive measurable benefit from treatment at the onset of symptoms. In most patients frequently recurrent disease can be suppressed with long-term therapy. Since long-term safety beyond 1 year has not been established, suppressive therapy should be stopped at least once per year to reassess the recurrence pattern. Acyclovir has not been adequately tested for safety in pregnancy and should not be prescribed for pregnant women unless the potential benefits outweigh the risks. Careful attention to disease severity, accurate diagnosis and exclusion of other causes of genital lesions will ensure that the drug is used only when beneficial.     

Uncoating the herpes simplex virus genome

Initiation of infection by herpes simplex virus (HSV-1) involves a step in which the parental virus capsid docks at a nuclear pore and injects its DNA into the nucleus. Once "uncoated" in this way, the virus DNA can be transcribed and replicated. In an effort to clarify the mechanism of DNA injection, we examined DNA release as it occurs in purified capsids incubated in vitro. DNA ejection was observed following two different treatments, trypsin digestion of capsids in solution, and heating of capsids after attachment to a solid surface. In both cases, electron microscopic analysis revealed that DNA was ejected as a single double helix with ejection occurring at one vertex presumed to be the portal. In the case of trypsin-treated capsids, DNA release was found to correlate with cleavage of a small proportion of the portal protein, UL6, suggesting that UL6 cleavage may be involved in making the capsid permissive for DNA ejection. In capsids bound to a solid surface, DNA ejection was observed only when capsids were warmed above 4 degrees C. The proportion of capsids releasing their DNA increased as a function of incubation temperature with nearly all capsids ejecting their DNA when incubation was at 37 degrees C. The results demonstrate heterogeneity among HSV-1 capsids with respect to their sensitivity to heat-induced DNA ejection. Such heterogeneity may indicate a similar heterogeneity in the ease with which capsids are able to deliver DNA to the infected cell nucleus.