Anti-herpes Simplex Virus Antibody Research Articles

1389 Local injection with anti-herpes simplex virus antibodies protects against development of herpes simplex virus–induced sweating disturbance

1389 Local injection with anti-herpes simplex virus antibodies protects against development of herpes simplex virus–induced sweating disturbance

Herpes simplex virus-associated esophagitis in a malnutrished patient : a case report

A 61-year-old man suffered from upper abdominal discomfort and appetite loss. He had underwent surgery of pharyngeal cancer the year before at the other hospital. Endoscopic examinations of upper gastrointestinal tract and colon revealed no abnormal findings. The patient also felt lower abdominal pain and had appendectomy next year. However, discomfort and pain on upper and lower abdomen unchanged and his fecal occult blood test was positive, he visited our hospital to survey metastasis of pharynx cancer by capsule endoscopy. The patient was nutritionally depleted, but immunologically unaffected. Capsule endoscopy showed multiple erosions and ulcers on small intestine. This time, upper abdominal endoscopy demonstrated geographical ulcers and erosions on esophageal mucosa. The biopsy specimens of the esophagus showed “ground glass” nuclei and positively immunostained with anti-herpes simplex virus antibody. According to nutritional improvement, the ulcers of esophagus disappeared endoscopically, together with a relief of upper abdominal discomfort. Simultaneously, the lower abdominal pain resolved and it was speculated that small intestinal lesions were also herpes simplex virus-associated. Because herpes simplex virus could affect all gastrointestinal tract, and the ulcers on capsule endoscopy resembled those on upper gastrointestinal endoscopy, aggressive endoscopic examinations are recommended, especially with longstanding symptom in the abdomen.

Characterization of Cullin-box Sequences That Direct Recruitment of Cul2-Rbx1 and Cul5-Rbx2 Modules to Elongin BC-based Ubiquitin Ligases

The Elongin BC-box protein family includes the von Hippel-Lindau tumor suppressor and suppressor of cytokine signaling proteins, which are substrate recognition subunits of structurally related classes of E3 ubiquitin ligases composed of Elongin C-Elongin B-Cullin 2-Rbx1 (Cul2 ubiquitin ligases) or of Elongin C-Elongin B-Cullin 5-Rbx2 (Cul5 ubiquitin ligases). The Elongin BC complex acts as an adaptor that links a substrate recognition subunit to heterodimers of either Cullin 2 (Cul2) and RING finger protein Rbx1 or Cullin 5 (Cul5) and Rbx2. It has been shown ( Kamura, T., Maenaka, K., Kotoshiba, S., Matsumoto, M., Kohda, D., Conaway, R. C., Conaway, J. W., and Nakayama, K. I. (2004) Genes Dev. 18, 3055-3065 ) that interaction of BC-box proteins with their cognate Cul-Rbx module is determined by specific regions, called Cul2- or Cul5-boxes, located immediately downstream of their BC-boxes. Here, we investigate further the mechanisms governing assembly of BC-box proteins with their specific Cul-Rbx modules. Through purification and characterization of a larger collection of BC-box proteins that serve as substrate recognition subunits of Cul2 and Cul5 ubiquitin ligases and through structure-function studies, we define Cul2- and Cul5-boxes in greater detail. Although it previously appeared that there was little sequence similarity between Cul5- and Cul2-box motifs, analyses of newly identified BC-box proteins reveal that residues conserved in the Cul2-box represent a subset of those conserved in the Cul5-box. The sequence motif LPPhiP, which is conserved in most Cul5-boxes and has been suggested to specify assembly of Cul5 ligases, is compatible with Cul2 interaction. Finally, the spacing between BC- and Cullin-boxes is much more flexible than has been appreciated and can vary from as few as 3 and as many as approximately 80 amino acids. Taken together, our findings shed new light on the mechanisms by which BC-box proteins direct recruitment of Cullin-Rbx modules during reconstitution of ubiquitin ligases.

Evidence for Antigen-Specific Immune Deviation in Patients With Acute Retinal Necrosis

Background: Because experimental acute retinal necrosis (ARN) induced by herpes simplex virus in mice develops only if mice fail to acquire virus-specific delayed hypersensitivity (DH), although they produce antiviral antibodies (ie, anterior chamber–associated immune deviation), we sought to determine whether a similar inverse correlation exists for patients with varicellazoster virus (VZV)-induced ARN. Design: Patients with acute, VZV-induced ARN and agematched control subjects were skin tested with VZV and purified protein derivative antigens to evaluate DH. Varicella-zoster virus–induced ARN was diagnosed using polymerase chain reaction and intraocular antibody quotient. Serum samples were collected and analyzed for anti-VZV and anti–herpes simplex virus antibody titers. Acute retinal necrosis activity was assessed clinically, and DH skin tests were repeated 3 months after onset when ocular recovery had taken place. Result: Whereas controls displayed intense DH when tested with VZV and purified protein derivative antigens, a subset of patients with ARN displayed absent VZV-specific DH (although their purified protein derivative responses were normal). Patients with the most severe ARN had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in patients with ARN than in controls, and antiviral titer correlated inversely with the intensity of anti-VZV DH responses. Varicella-zoster virus–specific DH responses were restored in patients who recovered from ARN. Conclusion: Varicella-zoster virus-ARN develops in a setting where DH reactivity to viral antigens is absent, implying that virus-specific DH might ameliorate the severity of ARN. Clinical Relevance: Linking virus-specific DH to vulnerability to ARN in individuals infected with VZV might reveal an underappreciated pathogenic mechanism.

A delay in CD4 cell response after initiation of highly active antiretroviral therapy is associated with the presence of anti-cytomegalovirus but not with anti-herpes simplex virus antibodies.

After the successful initiation of highly active antiretroviral therapy (HAART) in HIV-1-infected patients, the mean CD4 cell response was lower in cytomegalovirus (CMV)-seropositive patients than in CMV-seronegative patients (P < 0.05). The difference between the mean CD4 cell counts of CMV-seronegative and CMV-seropositive patients was maximal (163 x 10(6)/l) at 76 weeks after the start of HAART, and decreased gradually thereafter. No association was found between herpes simplex virus types 1 and 2 serostatus and CD4 cell response.

Identification of anti–herpes simplex virus antibody–producing B cells in a patient with an atypical RAG1 immunodeficiency

Mutations of the RAG1 or RAG2 protein that eliminate their recombination activity result in T-B-severe combined immunodeficiency (SCID), whereas mutations retaining partial recombination activity lead to Omenn syndrome, a peculiar SCID characterized by increased host T cells and absence of circulating B cells. The prognosis of this disease is fatal, unless hematopoietic stem cell transplantation is performed. This study reports a case of atypical SCID, carrying RAG1 mutations. The patient survived for 6 years without hematopoietic stem cell transplantation. The missense mutation, tested by in vivo recombination assay, revealed residual recombination activity. By the age of 5 years, the patient developed host B cells, but not T cells, possibly due to engrafted maternal T cells. In addition, the host B cells were able to produce antibodies, including anti-herpes simplex virus-antibodies. The fact that host B cells could produce antibodies in this patient could explain not only the mild phenotype observed but also, at least in part, how patients with Omenn syndrome produce immunoglobulin E and sometimes immunoglobulin M, as the same missense mutation of RAG1 gene has been reported in a patient with Omenn syndrome.

Evidence for antigen-specific immune deviation in patients with acute retinal necrosis.

Because experimental acute retinal necrosis (ARN) induced by herpes simplex virus in mice develops only if mice fail to acquire virus-specific delayed hypersensitivity (DH), although they produce antiviral antibodies (ie, anterior chamber-associated immune deviation), we sought to determine whether a similar inverse correlation exists for patients with varicella-zoster virus (VZV)-induced ARN. Patients with acute, VZV-induced ARN and age-matched control subjects were skin tested with VZV and purified protein derivative antigens to evaluate DH. Varicella-zoster virus-induced ARN was diagnosed using polymerase chain reaction and intraocular antibody quotient. Serum samples were collected and analyzed for anti-VZV and anti-herpes simplex virus antibody titers. Acute retinal necrosis activity was assessed clinically, and DH skin tests were repeated 3 months after onset when ocular recovery had taken place. Whereas controls displayed intense DH when tested with VZV and purified protein derivative antigens, a subset of patients with ARN displayed absent VZV-specific DH (although their purified protein derivative responses were normal). Patients with the most severe ARN had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in patients with ARN than in controls, and antiviral titer correlated inversely with the intensity of anti-VZV DH responses. Varicella-zoster virus-specific DH responses were restored in patients who recovered from ARN. Varicella-zoster virus-ARN develops in a setting where DH reactivity to viral antigens is absent, implying that virus-specific DH might ameliorate the severity of ARN. Linking virus-specific DH to vulnerability to ARN in individuals infected with VZV might reveal an underappreciated pathogenic mechanism.

Rapid strip assay for detection of anti-herpes simplex virus antibodies: application to prediction of varicella-zoster virus reactivation in patients with acute peripheral facial palsy.

Varicella-zoster virus (VZV) reactivation causes acute peripheral facial palsy in the majority (88%) of patients who lack anti-herpes simplex virus (HSV) antibodies, suggesting that an absence of anti-HSV antibodies is a reliable serological marker for the diagnosis of VZV reactivation in patients who are diagnosed initially as idiopathic peripheral facial palsy (Bell's palsy) [Furuta et al., 2000] Clinical Infectious Diseases]. A simple and rapid immunoassay for detection of anti-HSV antibodies based on HSV type 1 glycoprotein D was developed by modifying the conventional Western blot technique. The assay was evaluated by comparing the results with those of conventional Western blot. In total, 100 sera obtained from patients with acute peripheral facial palsy were tested and judged blindly by two investigators. Twenty-four of 26 HSV-seronegative sera were obtained from patients with VZV reactivation (Ramsay Hunt syndrome or zoster sine herpete). The sensitivity of the assay was over 95% and the specificity was 100%. The two investigators agreed on the diagnosis in 99 of the 100 sera. These results indicate that the rapid strip assay is applicable to prediction of VZV reactivation in patients diagnosed clinically with Bell's palsy before zoster lesions appear or PCR using saliva samples indicates VZV reactivation.

ガンシクロビルにて改善したウイルス脳炎の１例

A 57-year-old woman was admitted to our hospital with fever and lethargy. Cerebrospinal fluid (CSF) examination revealed pleocytosis and increased protein content. Immunological testing was positive for anti-herpes simplexvirus antibody and anti-cytomegalovirus antibody in each titer. Viral encephalitis was diagnosed and the patientwas initially treated with acyclovir, but was completely unresponsive to the drug. Since acyclovir was ineffective, the patient was switched to ganciclovir. This was followed by fever reduction and a decrease in CSF cell count. Theetiology of the encephalitis in this case was thought to be infection by acyclovir-resistant herpes simplex virus, ormixed infection by acyclovir-resistant herpes simplex virus and cytomegalovirus. When acyclovir is ineffective inviral encephalitis, ganciclovir may be the treatment of choice.

Relapse of Herpes Simplex Encephalitis in Children

The polymerase chain reaction method was used to diagnose herpes simplex encephalitis in children. Initial samples of cerebrospinal fluid from 15 patients with herpes simplex encephalitis were all positive for the herpes simplex virus DNA by polymerase chain reaction assay. In terms of early diagnosis, polymerase chain reaction assay became positive significantly earlier than the detection of intrathecally produced anti-herpes simplex virus antibody using the enzyme-linked immunosorbent assay (4.4 vs 8.9 days after onset; P less than .01). Serial examinations showed that the presence of virus DNA in cerebrospinal fluid continued for 3 to 18 days after the neurologic onset (mean 10.1 days). Four of the 15 patients had a relapse of encephalitis after completing acyclovir therapy. The mean duration of initial acyclovir therapy in the recurrent group was significantly shorter than that in the nonrecurrent group. In recurring cases, herpes simplex virus DNA reappeared temporarily in the cerebrospinal fluid of two patients. These results show that polymerase chain reaction assay is a useful diagnostic tool for the early and noninvasive diagnosis of herpes simplex encephalitis in children. Results also suggest that a comparatively short duration of acyclovir therapy may be related to a relapse of herpes simplex encephalitis in some children.

Simultaneous detection of antibodies to cytomegalovirus and herpes simplex virus by using flow cytometry and a microsphere-based fluorescence immunoassay.

A sensitive assay for the simultaneous detection of anti-cytomegalovirus and anti-herpes simplex virus antibodies was developed. Two different sizes of polystyrene microspheres were coated with purified viral antigens. Human antiviral antibodies were detected with a biotin-streptavidin amplification procedure with phycoerythrin as the fluorescent label. Microsphere-associated fluorescence was quantitated with a flow cytometer. Sixteen percent of samples initially scored as seronegative for cytomegalovirus and 35% of samples initially scored as seronegative for herpes simplex virus by conventional assays were clearly found positive by the microsphere technique. This flow cytometric assay can simultaneously detect several specific antibodies at levels which are below the sensitivity of standard assays. The dynamic range of this assay is at least sixfold greater than that of enzyme immunoassays. This technique is amenable to numerous serologic assays and could greatly expand the clinical laboratory applications of flow cytometry.

A Retrospective Analysis of Forty-Six Cases of Herpes Simplex Encephalitis Seen in Glasgow between 1962 and 1985

The clinical features, investigative profiles and outcome of 46 patients with biopsy or autopsy-proven herpes simplex encephalitis admitted to the Institute of Neurological Sciences, Glasgow between 1962 and 1985 were analysed retrospectively. The protean presenting symptoms and signs included a history of a prodromal influenza-like illness (48 per cent), rapid onset of headache, clouding of consciousness and confusion (52 per cent), meningism (65 per cent), raised intracranial pressure (33 per cent), deep coma (35 per cent), mutism or aphasia (46 per cent), focal neurological signs (89 per cent), and seizures (61 per cent). When seizures occurred they were almost always focal. The electroencephalogram was the most useful diagnostic test being abnormal in all cases, the majority showing focal changes in one or other hemisphere. Of the neuroradiological procedures employed, computerized tomographic and isotope brain scanning most frequently demonstrated localizing abnormalities in one or both temporal and/or frontal lobes. Midline shift was seen in half the cases. The cerebrospinal fluid was abnormal in every case but was not diagnostic. Cerebral biopsy of one temporal lobe was performed in 40 cases and a positive diagnosis of acute necrotizing encephalitis was made in 37 of these. Herpes simplex virus was isolated from the brains of 29 of the 40 cases in which the procedure was attempted, but immunofluorescence assays for antigens to herpes simplex virus were only positive in 11 out of 25 cases. Serological assays showed a greater than four-fold rise in the anti-herpes simplex virus antibody titre in 13 out of 22 patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoglobulin level in donor blood reactive for antibodies to human immunodeficiency virus.

Blood samples from 98 asymptomatic volunteer blood donors, including 55 that were reactive for antibodies to human immunodeficiency virus (HIV) in Western blot (WB) assay, were tested for levels of immunoglobulin G (IgG), IgM, and titer of antibodies to HIV, cytomegalovirus, and herpes simplex virus. Levels of IgG were significantly elevated (P less than or equal to 0.001) in donors with specific anti-HIV reactivity. A total of 69% of donors with anti-HIV had IgG levels of greater than or equal to 12 mg/ml, and 44% had IgG levels of greater than or equal to 14.5 mg/ml. Levels of IgM were not significantly different among WB-reactive and nonreactive donors. The titer of anti-HIV was significantly (P less than 0.02) correlated with IgG levels among donors reactive in the WB assay. Elevation of IgG, however, was not significantly associated with the presence of anticytomegalovirus or anti-herpes simplex virus antibodies. The data show that elevation of IgG may represent an early manifestation of HIV infection before the development of clinical symptoms of acquired immunodeficiency syndrome.

Defective production of anti-herpes simplex virus antibody by neonatal mice. Reconstitution with Ia+ macrophages and T helper lymphocytes from nonimmune adult syngeneic mice.

Both neonatal humans and mice are exquisitely susceptible to severe HSV infection. We have now documented a profound defect in the ability of neonatal C57BL/6 mice to produce anti-HSV ADCC antibody. This ability is acquired over the first 2 to 4 wk of life. Reconstitution of neonatal mice by i.p. injection of peritoneal cells from adult nonimmune syngeneic mice both affords dose-dependent protection against lethal HSV infection and reconstitutes the antibody-production defect. By cell-separation techniques (adherence, nylon wool column purification, B cell panning) and cell ablation techniques (silica treatment, irradiation, anti-T cell, anti-Ia, anti-Lyt-1.2 and anti-Lyt-2.2 monoclonal antibodies plus complement treatment) the subpopulations involved in the antibody production reconstitution of neonatal mice by adult cells were identified. These include both an Ia+, radioresistant, adherent, silica-sensitive macrophage population and a nylon wool column-purified, radiosensitive, anti-T, anti-Lyt-1.2-sensitive helper T cell population. The latter cell may be substituted for by concanavalin A-stimulated lymphokine-containing spleen cell supernatants or human recombinant IL 2. In addition to reconstitution of ADCC antibody production, the same cell populations, or cells plus lymphokine-containing supernatants or IL 2, protected the newborn mice from lethal HSV infection. Further characterization of this system and of soluble replacement factors has implications for therapy or immunoprophylaxis of human neonates with, or at risk of, HSV infection.

Acute follicular conjunctivitis and keratoconjunctivitis due to herpes simplex virus in London.

During the 18 months January 1975 to June 1976, 25 cases of acute herpetic follicular conjunctivitis and keratoconjunctivitis resembling adenovirus ocular infection presented in the External Eye Disease Clinic, Moorfields Eye Hospital, City Road, London. Herpes simplex virus was isolated in HEp2 cells in 22 patients, and the remaining 3 patients were identified by a minimum 4-fold rise in the level of antiherpes simplex virus antibody in their blood. No adenovirus was isolated from these patients, but complement fixation test for adenovirus was positive in 1 patient with cultural test positive for herpes simplex virus. Most patients were between 20 and 35 years old and the ratio of males to females was 12 to 13. At the initial visit the clinical features of disease were moderate to severe conjunctival papillary and follicular reasons with epithelial and subepithelial punctate keratitis but little systemic disease. In the absence of typical herpetic lesions of face, lids, or cornea the disease resembled adenovirus types 8 or 19 keratoconjunctivitis. Of these 25 patients 5 subsequently developed typical herpetic lesions of lids or cornea. In the remaining 20 cases the correct diagnosis could be made only by cultural or serological tests. Virological diagnosis provides a rational basis for antiherpetic chemotherapy, which appears to shorten the course of infection.

Effect of rheumatoid factor and anti-immunoglobulin G antibodies on complement-mediated lysis of herpes simplex virus-infected human fibroblasts

The effect of various anti-immunoglobulin G (IgG) antibodies on the complement-mediated lysis of herpes simplex virus-infected human fibroblasts was determined. IgM rheumatoid factor, a naturally occurring anti-human Fc, inhibited lysis, whereas rabbit anti-human IgG serum potentiated immune cytolysis. We attempted to explain this disparity by determining the effect various classess of anti-IgG's with differing specificities had on complement-mediated lysis. Inhibition of cytolysis occurred with IgM anti-Fc and all of the IgG antiglobulins (anti-IgG, Fab, and Fc). In contrast, IgM anti-Fab enhanced lysis. IgM anti-IgG suppressed immune cytolysis when high concentrations of antiviral serum were incubated with the virus-infected cell, but augmented lysis when low concentrations of anti-herpes simplex virus antibody were exposed to the fibroblasts. The experiments indicated that whether a particular antiglobulin potentiates or inhibits lysis depends on the concentration of antibody bound to the target cells as well as the class and specificity of the antiglobulin exposed to the antibody-coated cell.