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PubMed1980

Cell-mediated immunity to herpes virus type-1 in patients with recurrent corneal herpes simplex.

The proportion of T lymphocytes in the peripheral blood, their phytohaemagglutinin reactivity, and the leucocyte migration inhibitory effect of purified tuberculin protein were found to be equal in 25 recurrent corneal herpes simplex patients and 17 healthy individuals who had never suffered from clinically manifest herpes simplex virus (HSV) infection. Conversely, the HSV vaccine inhibited the leucocyte migration in the healthy group, but not in the recurrent herpes patients when the clinical symptoms were manifest. In 14 recurrent corneal herpes simplex patients, the examinations were repeated after a 3-month symptom-free period, and in these periods the patients corresponded equally to the healthy group in every respect.

Cell Migration Inhibition↗
PubMed1980

Serum antibodies to herpes simplex virus type 1 during active oral herpes infection.

Subjects with oral herpes lesions at the time of serum sampling had higher-efficiency antibody (higher proportion of neutralizing antibody as determined by plaque reduction, compared with total antibody as detected by radioimmunoassay) to herpes simplex virus type 1 (HSV-1) than did subjects with no lesions at the time of serum sampling. These higher-efficiency sera also had higher antibody titers to structural components of herpes simplex virus type 1 than did the low-efficiency sera. Absorption of high- and low-efficiency sera with purified herpes simplex virus type 1 particles removed all neutralizing antibody but not all antibody detected by radioimmunoassay. High-efficiency serum was depleted of more antibody to particulate antigen that was the low-efficiency serum, indicating that the high-efficiency serum contained a higher proportion of antibody to the virus particle.

Adult↗
PubMed1979

Herpes simplex virus glycoproteins: participation of individual herpes simplex virus type 1 glycoprotein antigens in immunocytolysis and their correlation with previously identified glycopolypeptides.

Tissue culture cells infected with herpes simplex type 1 virus express virus-specified glycoprotein antigens on the plasma membrane. Three of these have been previously identified and have been designated as Ag-11, Ag-8, and Ag-6. In the present study, immunoglobulins to each of the antigens were shown to be capable of mediating immunocytolysis in the presence of either complement (antibody-dependent complement-mediated cytotoxicity) or peripheral blood mononuclear cells (antibody-dependent cell-mediated cytotoxicity [ADCC]). Two herpes simplex virus type 1 strains, VR-3 and F, reacted similarly in the ADCC test in the presence of immunoglobulins to Ag-11, Ag-8, and Ag-6 in both infected Chang liver cells and HEp-2 cells. Anti-Ag-6, however, produced a lower ADCC reaction in HEp-2 cells than in Chang liver cells, suggesting differences in the Ag-6 surface expression in, or release from, these cells. Chang liver and HEp-2 cells infected with the MP mutant strain of herpes simplex virus type 1 showed reduced ADCC in the presence of anti-Ag-11 and anti-Ag-8, but no reactivity at all with anti-Ag-6. Crossed immunoelectrophoretic analysis showed that MP-infected cell extracts contain Ag-11 and Ag-8, but lack Ag-6. Polypeptide analysis of herpes simplex virus type 1 strains F, VR-3, and MP showed that Ag-11 consists of the glycoproteins gA and gB, that Ag-8 consists of gD, and that Ag-6 consists of gC. In conclusion, the present study demonstrates that either one of the glycoproteins (gC, gD, and a mixture of gA and gB) can function as a target for immunocytolysis and that the antibody preparation to gC (Ag-6) does not cross-react with any of the other glycoproteins.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1982

Secretory IgA specific for herpes simplex virus in lacrimal fluid from patients with herpes keratitis--a possible diagnostic parameter.

In the present study a solid-phase radioimmune assay was used for the demonstration of herpes simplex virus-specific IgG and secretory IgA antibodies in the lacrimal fluid from patients with active recurrent herpes keratitis. The method was quantitative and made it possible to test specifically for the production of secretory IgA antibodies produced during an active herpes simplex virus infection. The production of secretory IgA was followed in 2 patients with fresh recurrent lesions. The HSV-specific secretory IgA could be demonstrated during the first 10 days of infection, where the maximal concentration was reached 3-5 days after the first symptoms occurred. The secretory antibodies were locally produced, and it is shown for the first time that herpes virus-specific secretory antibodies were of diagnostic value.

Adult↗
PubMedDate not supplied

[Effect of the herpes simplex virus antigen on E rosette formation by the lymphocytes of patients with ocular herpes].

Herpes simplex virus antigen was demonstrated to inhibit E-rosette formation in most cases of herpetic eye infection in contrast to those of adenovirus eye infection or healthy donors in whom inhibition of spontaneous E-rosette formation in the presence of herpes virus antigen is observed much more rarely. It is suggested that inhibition of E-rosette formation is associated with specific sensitivity of lymphocytes of the subjects under study to herpes antigen. It is also suggested that spontaneous E-rosette formation may be used to determine the degree of T-lymphocyte response to herpes virus antigen.

Adenovirus Infections, Human↗
PubMed1982

The use of herpes virus induced dTk as a marker for serological and direct identification of herpes virus infection in man.

This report summarizes the essential features of a sensitive deoxythymidine kinase (dTk) assay, which can be used for the diagnosis of Herpes virus infections. A type specific antibody response towards the different Herpes virus dTk isozymes, the Herpes simplex virus (HSV) type 1, type 2, and Varicella Zoster virus (VZV), was found in human sera. The occurrence of dTk antibody in relation to complement fixing (cf) antibody and the state of infection, was found to differ between HSV and VZV. The VZV dTk antibody was only found in patients with Herpes Zoster, while most HSV cf positive individuals had HSV dTk antibody. Absence of dTk in HSV cf positive individuals was related to a "recent primary infection". The type specificity of the dTk isozymes makes these antigens suitable for typing of isolates, and this in combination with the sensitivity of the assay, made it possible to verify and type HSV infection by direct analysis of blister secrete without previous virus isolation. Such results can be obtained within five hours. Combined with conventional isolation procedures the dTk typing assay also detects dTk negative "therapy resistant" strains. The use of the dTk assay for diagnostic purposes is discussed.

Antibodies↗
PubMed1981

Herpes simplex type 1 retinitis in an adult with systemic herpes zoster.

A 72-year-old man developed bullous skin lesions two months before he was discovered to have malignant lymphoma. Herpes zoster virus grew from the skin bullae. He developed encephalitis, keratitis in the left eye, and bilateral retinitis 18 months later. Herpes simplex virus type 1 grew from cultures of the eyelid vesicles and corneal scrapings from the left eye. The patient died two years after the diagnosis of malignant lymphoma. Virus particles believed to be herpes simplex virus were demonstrated on electron microscopy in the necrotic retinal cells.

Aged↗
PubMed1990

Epidemiology of genital herpes in Pittsburgh: serologic, sexual, and racial correlates of apparent and inapparent herpes simplex infections.

Women attending family planning clinics in western Pennsylvania were enrolled into a prospective epidemiologic study of herpes simplex virus (HSV) infection. Detection of antibodies to HSV-1 and HSV-2 was based on an immunodot assay using type-specific glycoproteins gG-1 and gG-2. Serologic and historical data at enrollment were analyzed for 4527 subjects; the seroprevalence of HSV-2 was 21.6%. By multivariate analysis, HSV-2 infection as determined by seroprevalence was significantly and independently associated with age, years of sexual activity, race, one or more episodes of other genital infections, lower annual family income, and multiple sexual partners. The presence of antibody to HSV-1 was associated with a lower frequency of antibody to HSV-2, suggesting that developed immunity to HSV-1 protected against HSV-2 infection. Of 926 participants who had antibody to HSV-2, only 117 (12.6%) reported a history of genital herpes. Hence the vast majority of HSV-2 infections were inapparent. Although seroprevalence of HSV-2 was higher among black (35.4%) than white (18.5%) women, black women appeared to have significantly less symptomatic genital herpes than white women (7.7% vs. 14.7%, P less than .01).

Adolescent↗
PubMed1997

Genital herpes in a primary care clinic. Demographic and sexual correlates of herpes simplex type 2 infections.

BACKGROUND AND OBJECTIVES: Genital herpes remains one of the most prevalent sexually transmitted diseases (STDs). The sexual behavioral correlates of herpes simplex virus type 2 (HSV-2) infection in the general population have not been well characterized. GOALS: To assess demographic and sexual behavioral correlates of symptomatic and subclinical HSV-2 infection. STUDY DESIGN: Cross-sectional survey of 922 randomly chosen patients and 78 of their partners (1,000 total) in a family practice. Sexual behavior information was collected in 492 people. RESULTS: Two hundred twenty-five (23%) heterosexual people had HSV-2 infection, but only 59 (26%) reported a history of genital herpes. HSV-2 seroprevalence was 63% in African-American women, 27% in white women, 40% in African-American men, and 12% in white men. In multivariate analyses of risk factors for HSV-2 infection among men, 10 or more sexual partners and a prior STD were statistically significantly associated with HSV-2 infection. Among white women, number of sexual partners, a prior STD, marriage or cohabitation, and less than a college education were predictive of HSV-2 infection. A history of oral sex was the only statistically significant predictor of HSV-2 infection in African-American women. CONCLUSIONS: Risk factors for HSV-2 infection differ by gender and ethnic group. Traditionally recognized behavioral correlates of STD acquisition may not identify people in communities with high prevalence of HSV-2 infection.

Adolescent↗
PubMed2004

Duplex real-time polymerase chain reaction assay for detection and quantification of herpes simplex virus type 1 and herpes simplex virus type 2 in genital and cutaneous lesions.

BACKGROUND: A sensitive and specific method for detecting herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) is important for diagnosing genital and cutaneous infections. GOAL: The goal of this study was to compare quantitative real-time polymerase chain reaction (qPCR) with virus culture for diagnosis of genital and cutaneous HSV-1 and HSV-2. STUDY DESIGN: A duplex qPCR system for quantification of DNA from HSV-1 and HSV-2 was developed. Duplicate swabs for PCR and virus culture were collected from 89 patients attending our sexually transmitted infection and dermatology clinic. RESULTS: The duplex qPCR had a linear measure interval of 10-10 copies/mL. The detection limit was between 1 and 5 copies per reaction. qPCR detected HSV in 57 (64%) specimens and virus was isolated in 45 (50%) cases. First-episode infections showed higher viral quantities with a median value of 4.2 x 10 copies per reaction compared with recurrent infections with 1.0 x 10 (P = 0.0002). HSV-1 was more likely to be the cause of first-episode genital infections (72%), and HSV-2 of recurrent and atypical genital manifestations (73%). CONCLUSION: Real-time PCR is a sensitive method for diagnosing genital herpes, and the duplex format is convenient for typing. The method increased the detection rate by 27% compared with virus culture.

Adolescent↗
PubMed2004

Seroprevalence and seroincidence of herpes simplex virus type 1 and herpes simplex virus type 2 infections in a cohort of adolescents in Italy.

OBJECTIVE: The objective of this study was to improve the knowledge on the epidemiology of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) in Italy. GOAL: The goal of this study was to study the seroincidence and seroprevalence of HSV-1 and HSV-2 infections among Italian adolescents. STUDY: We conducted a retrospective longitudinal study among 345 Italian adolescents tested for anti-HSV-1 and anti-HSV-2 on samples collected at 11 and 17 years of age. RESULTS: At 11 years of age, the HSV-1 prevalence was 51.6% and the HSV-2 prevalence was 2.6%; when 17 years old, these rates increased to 61.4% and 4.9%, respectively. The HSV-1 incidence was 1.6 per 100 person-years and was higher among females. The HSV-2 incidence was 0.4 per 100 person-years with no gender differences. CONCLUSION: HSV-1 is apparently widespread among Italian adolescents, whereas HSV-2 is limited. These data are of paramount importance when considering that HSV-1 can cause genital herpes and that HSV-2 plays a role in HIV transmission.

Adolescent↗
PubMed1975

Viral warts, herpes simplex and herpes zoster in patients with secondary immune deficiencies and neoplasms.

The incidence of viral warts, recurrent herpes simplex and herpes zoster has been assessed in a group of patients with possible secondary immune deficiency states and compared to a control group. Patients with cell-mediated immune deficiency appear to be more prone to warts and zoster infection as compared to patients with humoral immune deficiency. Recurrent herpes simplex infection was not increased in either group.

Adolescent↗
PubMed1994

Safety of famciclovir in patients with herpes zoster and genital herpes.

Safety reporting from individual ongoing and completed clinical studies has demonstrated that famciclovir, the well-absorbed oral form of the antiherpesvirus agent penciclovir, has been well tolerated by more than 3,000 individuals worldwide. An integrated safety evaluation has been performed and includes over 1,600 patients from 11 completed, randomized, double-blind clinical trials and 2 open trials. The famciclovir population consisted of 816 herpes zoster patients (four trials), 409 patients with acute genital herpesvirus infections (seven trials), and 382 patients from two genital herpes suppression studies. Overall, the famciclovir-treated patient population was 57.7% female and ranged in age from 15 to 102 years (mean, 42.6 years), with 31.2% aged 50 years or more and 15.7% aged 65 years or more. The mean duration of exposure to famciclovir was 28.8 days (5.8 days excluding suppression studies). The total daily doses ranged from 125 mg to 2.25 g. The most common adverse experiences reported as related to study medication (famciclovir and placebo) were headache, nausea, and diarrhea. The frequencies of adverse experiences and laboratory abnormalities (hematology, clinical chemistry, and urinalysis parameters) were similar in both famciclovir and placebo recipients. Thus, safety data from the analysis of 13 completed clinical studies demonstrate that famciclovir is tolerated well by patients with either herpes zoster or genital and has a safety profile comparable to that of placebo.

2-Aminopurine↗
PubMed1998

Recognition of herpes simplex virus type 2 tegument proteins by CD4 T cells infiltrating human genital herpes lesions.

The local cellular immune response to herpes simplex virus (HSV) is important in the control of recurrent HSV infection. The antiviral functions of infiltrating CD4-bearing T cells may include cytotoxicity, inhibition of viral growth, lymphokine secretion, and support of humoral and CD8 responses. The antigens recognized by many HSV-specific CD4 T cells localizing to genital HSV-2 lesions are unknown. T cells recognizing antigens encoded within map units 0. 67 to 0.73 of HSV DNA are frequently recovered from herpetic lesions. Expression cloning with this region of DNA now shows that tegument protein VP22 and the viral dUTPase, encoded by genes UL49 and UL50, respectively, are T-cell antigens. Separate epitopes in VP22 were defined for T-cell clones from each of three patients. Reactivity with the tegument protein encoded by UL21 was identified for an additional patient. Three new epitopes were identified in VP16, a tegument protein associated with VP22. Some tegument-specific CD4 T-cell clones exhibited cytotoxic activity against HSV-infected cells. These results suggest that herpes simplex tegument proteins are processed for antigen presentation in vivo and are possible candidate compounds for herpes simplex vaccines.

Amino Acid Sequence↗
PubMed1998

Oral famciclovir for the suppression of recurrent genital herpes: a randomized controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

CONTEXT: Recurrent genital herpes simplex virus (HSV) may be treated episodically, but this may not be sufficient for patients with frequent recurrences. OBJECTIVE: To determine the efficacy and safety of famciclovir in the suppression of recurrent genital HSV infection. DESIGN: A randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Thirty university, hospital, or private outpatient referral centers in Canada and Europe. PATIENTS: A total of 455 patients (223 men, 232 women) aged 18 years or older with a history of 6 or more episodes of genital herpes during 12 of the most recent 24 months, in the absence of suppressive therapy, received study medication. INTERVENTION: Oral famciclovir, 125 mg or 250 mg 3 times daily or 250 mg twice daily, or placebo for 52 weeks. MAIN OUTCOME MEASURES: Time to the first recurrence of genital HSV infection; the proportion of patients remaining free of HSV recurrence at 6 months; frequency of adverse events. RESULTS: In an intent-to-treat analysis, famciclovir significantly delayed the time to the first recurrence of genital herpes at all dose regimens (hazard ratios, 2.9-3.3; P<.001); median time to recurrence for famciclovir recipients was 222 to 336 days compared with 47 days for placebo recipients. The proportion of patients remaining free of HSV recurrence was approximately 3 times higher in famciclovir recipients (79%-86%) than in placebo recipients (27%) at 6 months (relative risks, 2.9-3.1; P<.001); efficacy was maintained at 12 months. Famciclovir was well tolerated with an adverse experience profile comparable to placebo. CONCLUSIONS: Oral famciclovir (125 mg or 250 mg 3 times daily or 250 mg twice daily) is an effective, well-tolerated treatment for the suppression of genital HSV infection in patients with frequent recurrences.

2-Aminopurine↗
PubMed2001

Herpes simplex virus type 1 (HSV-1)--induced retinitis following herpes simplex encephalitis: indications for brain-to-eye transmission of HSV-1.

Herpes simplex encephalitis is a severe neurological disease with high mortality and morbidity rates. Reactivated herpes simplex virus type 1 (HSV-1) can cause relapses and might even spread to the retina, where it can induce a potentially blinding eye disease, known as acute retinal necrosis. In the present study, the HSV-1 strains in the brain and eye of 2 patients with acute retinal necrosis following an episode of herpes simplex encephalitis were genotyped. The HSV-1 strains in both the brain and eye were identical in each patient, but they differed interindividually. The data suggest brain-to-eye transmission of HSV-1 in these patients.

Aged↗
PubMed1988

History of recurrent mucocutaneous herpes correlates with relatively low interferon production by herpes simplex virus-exposed cultured monocytes.

Monocytes separated from blood specimens of healthy voluntary blood donors were infected with herpes simplex virus (HSV) 1 or 2. The amount of interferon produced by the HSV-exposed monocytes was found to be donor-specific and was similar whether tested with HSV 1 or HSV 2. The interferon levels in repeated blood specimens from a given donor were relatively stable within an observation period of a few months. The survey was expanded by testing 27 persons with history of recurrent herpes disease and 16 control persons without such history. HSV-exposed monocytes of the controls produced significantly higher amounts of interferon than those of the patients with lesions of recurrent herpes (mean levels 145 and 58 IU/ml, respectively; P less than 0.05). A correlation was also found between the antibody status of the cell donor and the capability of the monocytes to produce interferon when infected with HSV 1 or HSV 2: the interferon responses of monocytes of seronegative cell donors were significantly higher than those of cultures from donors with complement fixing antibodies against HSV (P less than 0.01).

Antibodies, Viral↗
PubMed1986

Anti-herpes simplex type 1 activity in IgG subclasses produced systemically and intrathecally in patients with herpes encephalitis.

The role of the humoral immune response in herpes simplex encephalitis (HSE) is largely unknown. The finding that herpes simplex virus type 1 (HSV 1) induced IgG Fc receptor binds to all IgG subclasses except IgG 3 prompted an investigation of anti-HSV activity in IgG subclasses from serum and cerebrospinal fluid (CSF) in ten patients with proven or highly probable HSE by means of a monoclonal antibody IgG subclass-specific solid-phase radioimmunoassay (SPRIA). In contrast to serum, CSF contained no or low anti-HSV IgG titres during the first 2 weeks of disease in five of seven patients tested. The IgG titres rose thereafter for at least 4 weeks after the start of illness and remained high in both serum and CSF up to 393 days. The anti-HSV IgG subclass distribution in serum was IgG 1 (ten of ten), IgG 2 (two of ten), IgG 3 (six of ten), and IgG 4 (six of ten). Two patients had a simultaneous anti-HSV IgG 3 and IgG 4 response. With the exception of one patient lacking anti-HSV IgG 4 and two patients lacking anti-HSV IgG 2, the subclass distribution in CSF was the same as in serum. The anti-HSV subclass distribution in sera from ten seropositive patients without evidence of recent herpes infection did not differ from that of the HSE patients, except that five of ten patients had simultaneous anti-HSV IgG 3 and IgG 4 responses. Thus we could not correlate the anti-HSV subclass response in patients with HSE with the subclass preference of the HSV-induced Fc receptor.

Adult↗