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PubMed1985

Comparison of the detection of herpes simplex virus in direct clinical specimens with herpes simplex virus-specific DNA probes and monoclonal antibodies.

A comparison of two commercially available kits for rapid herpes simplex virus (HSV) detection directly in patient specimens was performed. The immunofluorescence assay (IFA) utilized monoclonal antibodies to HSV, and the DNA probe assay utilized three HSV sequences cloned into pBR322. A sample of 243 specimens received in viral transport medium were inoculated into MRC-5 tissue cultures. The remainder of the specimen was centrifuged, and the cellular pellet was examined by IFA and DNA probes. One hundred and sixty-two (66.7%) specimens were considered satisfactory for IFA and DNA probe testing, based on a criterion of observing greater than or equal to 2 intact cells per high-power field. Of the 162 specimens, 35 (21.6%) yielded HSV by culture. By IFA, the sensitivity of detecting HSV culture-positive specimens was 77.1%; specificity was 100%, positive predictive value was 100%, and negative predictive value was 93.3%. DNA probe sensitivity was 71.4%; specificity was 90.6%; positive predictive value was 67.6%; and negative predictive value was 92%. Forty-four (27.2%) of the 162 specimens exhibited nonspecific cytoplasmic staining with the DNA probe. IFA and DNA probe assays can be completed in 2 to 3 h, whereas the average time to culture positivity in this series was 2.2 days. Rapid HSV diagnosis can aid in timely and appropriate patient management.

Antibodies, Monoclonal↗
PubMed1978

Protective effect of an oral infection with herpes simplex virus type 1 against subsequent genital infection with herpes simplex virus type 2.

The problem of whether oral Herpes simplex virus type 1 (HSV-1) infection provides protection against subsequent genital infection by Herpes simplex virus type 2 (HSV-2) was investigated. Mice were used as models. Following conditions in man, both the oral and genital infections applied were noninjurious. Mice infected orally with HSV-1 were weakly protected against virus 'take' following vaginal challenge with HSV-2. Genital 'takes' were found in 67% of the immunized mice, as compared with 83% of the controls (protection rate 20%, P = 0.002). The course of genital infection in the immunized mice, however, was relatively mild: Lethality decreased from 97% in the controls to 35% in the immunized mice (protection rate 63%, P less than 0.001). Furthermore, local and neurologic symptoms occurred less frequently. Attempts to isolate the virus from homogenized brain and spinal cord of immunized mice that died after genital challenge with HSV-2 failed in most cases. Also virus could not be recovered from the liver of infected mice, irrespective of the experimental group.

Animals↗
PubMed1987

Detection of antibodies to herpes simplex virus in the cerebrospinal fluid of patients with herpes simplex encephalitis.

Cerebrospinal fluid (CSF) and serum specimens from patients with presumed herpes simplex encephalitis (HSE) were characterized for antibodies to herpes simplex virus (HSV) by immunoblot and other immunoassays. Specimens from patients proven to have HSE (biopsy-proven) were compared with those from patients with other diseases diagnosed by brain biopsy (biopsy-negative for HSV). Immunoblot of CSF demonstrated that antibodies to HSV-specific polypeptides, particularly to glycoprotein B, were present in a matched serum specimen. When purified glycoprotein B was used to detect CSF antibodies, 34 of 35 specimens from biopsy-proven patients were reactive (97% sensitivity) compared with only six of 22 specimens obtained from biopsy-negative patients (73% specificity). If leakage of antibodies to a marker virus (adenovirus) was determined and controlled, the specificity increased to 100%. These diagnostic assays provide useful tools for the retrospective assessment of CSF specimens obtained from patients with presumed HSE.

Adolescent↗
PubMed1990

Serum and cerebrospinal fluid herpes simplex virus type 1 immunoglobulin G and M titers in four cases of herpes simplex encephalitis.

Herpes simplex virus type 1 (HSV-1) IgG and IgM ELISA titers were serially determined in serum and cerebrospinal fluid (CSF) samples from 4 patients with HSV-1 encephalitis during a follow-up period of 1-26 months. In 3 out of 4 patients HSV-1 IgM titers raised in CSF during the acute phase of disease, thus allowing differentiation between primary and reactivated forms of HSV-1 encephalitis. HSV-1 IgG titers showed a sharp elevation earlier in serum than in CSF. Specific IgG index documented a large intrathecal production of HSV-1 IgG and their persistence 2 years following clinical onset. The initial trend of serum and CSF specific IgG titer represents a reliable tool for a retrospective diagnosis of HSV-1 encephalitis.

Antibodies, Viral↗
PubMed1997

Characterization of T cell responses to herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) using a TNF-beta ELISpot cytokine assay.

We examined the suitability of a TNF-beta cytokine ELISpot assay for assessing various aspects of the T cell response to herpes simplex viruses. The number of T cells responding to HSV-1 or HSV-2 was measured by TNF-beta ELISpot assay. The number of T cells producing TNF-beta in response to HSV-1 was high, ranging from 76 to 222 per 10(5). HSV-1-specific TNF-beta-secreting responder cell frequencies fluctuated over time in individual donors. Comparable fluctuations were not observed in the T cell frequencies to phytohemaglutinin (PHA). Responder cell frequencies to glycoproteins gB and gD of HSV-2 accounted for a large number of the HSV-2-specific T cells as measured using the TNF-beta ELISpot assay. Type-specific and type-common components of the T cell response to HSV-1 and HSV-2 could be estimated with this assay. Type-common responder cells typically accounted for 25-30%. Finally, CD4+ and CD8+ TNF-beta-producing T cells were stimulated by HSV-1 at a CD4:CD8 ratio of 2:1, indicating that both major subsets of T lymphocytes are activated by HSV.

Animals↗
PubMed1997

Quantitation of herpes simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis by the polymerase chain reaction.

BACKGROUND: Previous studies have shown the diagnostic utility of qualitative detection of herpes simplex virus (HSV) DNA by the polymerase chain reaction (PCR) in cerebrospinal fluid samples (CSF) from patients with herpes simplex encephalitis (HSE). OBJECTIVES: To determine whether quantitation of HSV DNA in CSF could be useful for monitoring efficacy of antiviral therapy and provide prognostic indications. STUDY DESIGN: A quantitative PCR assay using an internal control for evaluation of PCR efficiency and detection of PCR inhibitors was developed and used for retrospective testing of 98 CSF samples from 26 patients with serologically diagnosed HSE during the period 1980-1995. RESULTS: HSV DNA was detected in 36 CSF samples from 23 patients. PCR positivity was 100% for CSF samples collected within 10 days after onset, and 30.4 and 18.7% for samples collected 11-20 and 21-40 days later, respectively. The 3 PCR-negative patients had their first CSF collected 14, 16, and 28 days after onset, respectively. Three of 98 (3.1%) CSF samples were completely or partially inhibitory to PCR. Initial DNA levels were not significantly different in patients with HSE due to either primary or recurrent HSV infection. In addition, they were not related to severity of clinical symptoms nor were predictive of the outcome. A progressive decrease in viral DNA levels was observed both in patients who received acyclovir therapy and in a small number of untreated patients. CONCLUSIONS: This study: (i) confirms the high sensitivity of PCR for the diagnosis of HSE; (ii) emphasizes the need for an internal control of amplification of achieve maximal sensitivity and perform reliable quantitation of viral DNA; and (iii) suggests that CSF might not be the best specimen to investigate in studies of the natural history of HSE.

Adolescent↗
PubMed1996

Herpes simplex encephalitis.

Herpes simplex encephalitis (HSE) is a life-threatening condition with high mortality as well as significant morbidity in survivors. In most cases herpes simplex virus type 1 (HSV-1) is responsible for the diseases, however, the type 2 virus (HSV-2) is involved in 4-6% of cases. Primary HSV infection is identified in only one-third of patients with HSE. The majority of cases are recorded in adults with recurrent HSV infection who are already seropositive for HSV at the onset of symptoms, but only 6-10% of these patients have a history of labial herpes. Acute focal, necrotizing encephalitis with inflammation and swelling of the brain tissue are consistent features of the pathology of HSE. HSV-induced cytolysis certainly damages neurones, oligodendrocytes and astrocytes, but the role of cellular and humoral immunopathology is important. A complex network of cytokines seems to be active in regulating the local immune response and inflammation during and after HSE. Brain biopsy, serological analysis of intrathecal HSV antibodies and detection of HSV-DNA in the cerebrospinal fluid (CSF) are all useful techniques to confirm the aetiology of HSE. Neurodiagnostic tests which support a presumptive diagnosis of HSE include: CSF analysis, electroencephalography, computer-assisted tomography and magnetic resonance imaging. Although aciclovir is the treatment of choice in HSE, mortality and morbidity still remain problematic. Long-term follow-up indicates that intrathecal cellular and humoral activation persist in HSE.

Acyclovir↗
PubMed1989

A case study of the cognitive and behavioral deficits of temporal lobe damage in herpes simplex encephalitis.

Herpes simplex viral encephalitis is a fairly common nonepidemic encephalitis which produces severe neurological sequelae in survivors. Most viral infections of the central nervous system produce diffuse damage, but the herpes simplex virus demonstrates a predilection for localization in the temporal and orbitofrontal regions of the brain. This case study illustrates the highly significant language difficulties, marked memory deficits, and propensity for physical aggression following temporal lobe damage brought about by herpes encephalitis, and presents the usefulness of a new diagnostic measure in delineating such a variable cognitive pattern.

Adolescent↗
PubMed1991

Seroepidemiology of herpes simplex virus and restriction endonuclease cleavages analysis of herpes simplex virus type 2 in Okinawa.

A seroepidemiologic study of herpes simplex virus (HSV) in Okinawa was performed. A total of 423 serum samples were collected from all over Okinawa, and the positivity rate of antibody against HSV was measured using a passive hemagglutination method. The sero-positive rate for HSV in age groups of over 40 years was 100%. Seven HSV type 2 (HSV 2) isolates were obtained in Okinawa, and DNA preparations from Vero cells infected with the isolates were analyzed using five restriction endonucleases: Bam HI, Hind III, Kpn I, Bgl II and Eco RI. Variations in the genomic region were demonstrated in five of the isolates. Such variations have not been reported previously in HSV 2 in mainland Japan. This is the first report of a seroepidemiologic study of HSV and restriction endonuclease cleavage analysis of HSV 2 in Okinawa, is a subtropical island where HSV is endemic.

Adolescent↗
PubMed1981

Mechanisms of expression of herpes simplex virus-common surface antigens in clonal cells of a herpes simplex virus type 2-transformed line.

Rabbit antiserum hyperimmune to herpes simplex virus type 1 was used to study the expression of herpes simplex virus type-common surface antigens (CSA) by indirect immunofluorescence tests in three representative cell clones isolated from a herpes simplex virus type 2-transformed hamster line, 155-4. These three clones showed different phenotypes with respect to CSA expression: (i) a CSA-positive type (clone (155-4-213), in which the antigens increased soon (5 h) after seeding at 37 degrees C, but not after treatment with actinomycin D; (ii) a CSA-inducible type (clone 155-4-03), in which the antigens increased after treatment with actinomycin D (2 micrograms/ml) for 20 h, but not after seeding only; and (iii) a CSA-negative type (clone 155-4-16), in which the antigens did not increase after seeding or after actinomycin D treatment. CSA expression in the CSA-positive type was inhibited by 2-deoxy-D-glucose, but not by puromycin, suggesting that the expression required glycosylation, but not active protein synthesis. CSA expression in this type was insensitive to the protease inhibitors antipain and p-nitrophenyl-p'-guanidinobenzoate. On the other hand, actinomycin D-induced CSA expression in the CSA-inducible type was inhibited by both 2-deoxy-D-glucose and puromycin, suggesting that the induced expression required both glycosylation and protein synthesis. CSA expression induced in this type was sensitive to the two protease inhibitors at concentrations having little effect on overall cellular metabolism or cell viability. These results indicate that CSA expressions in the CSA-positive type and the CSA-inducible type are enhanced by different mechanisms.

Animals↗
PubMed1989

Herpes simplex virus glycoprotein D mediates interference with herpes simplex virus infection.

We showed that the expression of a single protein, glycoprotein D (gD-1), specified by herpes simplex virus type 1 (HSV-1) renders cells resistant to infection by HSV but not to infection by other viruses. Mouse (LMtk-) and human (HEp-2) cell lines containing the gene for gD-1 under control of the human metallothionein promoter II expressed various levels of gD-1 constitutively and could be induced to express higher levels with heavy metal ions. Radiolabeled viruses bound equally well to gD-1-expressing and control cell lines. Adsorbed viruses were unable to penetrate cells expressing sufficient levels of gD-1, based on lack of any cytopathic effects of the challenge virus and on failure to detect either the induction of viral protein synthesis or the shutoff of host protein synthesis normally mediated by a virion-associated factor. The resistance to HSV infection conferred by gD-1 expression was not absolute and depended on several variables, including the amount of gD-1 expressed, the dosage of the challenge virus, the serotype of the challenge virus, and the properties of the cells themselves. The interference activity of gD-1 is discussed in relation to the role of gD-1 in virion infectivity and its possible role in permitting escape of progeny HSV from infected cells.

Animals↗
PubMed1980

CT in the early diagnosis of herpes simplex encephalitis.

Herpes simplex is the most common cause of sporadic viral encephalitis. The recent development of specific antiviral chemotherapeutic agents offers new optimism for patients with this disorder if therapy is begun on or before the fifth day of the disease. Eight patients with herpes simplex encephalitis were studied by CT, and a characteristic but not pathognomonic pattern was observed. In each case a low density lesion was noted in the medial portion of the temporal lobe with extension into the Island of Reil. Sparing of the lenticular nucleus was observed in all cases. Mass effect and streaky linear enhancement after contrast administration was also seen. Unfortunately, the findings may be subtle or absent before the fifth day of disease, and thus CT scans must be examined with a high index of suspicion if the correct diagnosis is to be made at a time when therapy may prove useful. Hemorrhagic areas are rarely observed on CT in this disorder despite the frequent occurrence on pathologic studies. The full extent of involvement may not be appreciated on scans obtained during the first 10 days of the disease.

Adult↗
PubMed1983

Susceptibility of recent clinical isolates of herpes simplex virus to 5-ethyl-2'-deoxyuridine: preferential inhibition of herpes simplex virus type 2.

We examined the in vitro susceptibilities of three reference strains and 41 recent clinical isolates of herpes simplex virus types 1 and 2 to 5-ethyl-2'-deoxyuridine. This thymidine analog exerts a type 2-preferential but not a type 2-specific antiviral effect. Utilizing a microtiter assay with BHK-21 cells, we found that the mean (+/- standard deviation) 50% inhibitory dose for herpes simplex virus type 1 isolates was 0.58 +/- 0.30 micrograms/ml as compared with 0.33 +/- 0.20 microgram/ml for herpes simplex virus type 2 isolates. Isolates were typed according to their susceptibilities to (E)-5-(2-bromovinyl)-2'-deoxyuridine and by an indirect fluorescent-antibody technique in which monoclonal antibody combinations were used. A cytotoxicity assay in which the incorporation of [1',2'-3H]deoxyuridine was measured revealed a 50% inhibitory dose of 37.5 micrograms/ml, suggesting a favorable therapeutic index for this compound.

Antibodies, Monoclonal↗
PubMed2004

Update on herpes simplex encephalitis.

Herpes simplex encephalitis is the most common identified cause of sporadic viral encephalitis in the United States. Early diagnosis is critical because treatment with the antiviral drug acyclovir dramatically decreases morbidity and mortality. The use of polymerase chain reaction (PCR) techniques to amplify the genome of herpes simplex virus (HSV) from cerebrospinal fluid (CSF) has become the diagnostic procedure of choice. False-positive CSF HSV PCR results are rare when testing is performed in experienced laboratories. Negative CSF HSV PCR results should always be interpreted in the context of the timing of specimen collection and the likelihood of disease. Negative CSF HSV PCR tests can occur within the first 72 hours of illness, with subsequent tests becoming positive. Patients with HSV encephalitis will typically have a negative CSF HSV PCR after 14 days of acyclovir treatment, and a persisting positive PCR should prompt consideration of additional or revised antiviral therapy. Quantitative PCR testing provides information about HSV viral load in CSF, but the potential correlation of viral load with prognosis or other clinical features of disease remains uncertain. Although the neuroimaging abnormalities seen in HSV encephalitis are not unique, more than 90% of patients with proven HSV encephalitis will have magnetic resonance imaging (MRI) abnormalities involving the temporal lobes. Special MRI techniques, including fluid-attenuated inversion recovery and diffusion-weighted imaging, might reveal abnormalities not seen with conventional imaging sequences. Neuroimaging patterns in infants and children differ significantly from those seen in adults and include a higher frequency of extratemporal lesions.

Acyclovir↗
PubMed1996

Molecular diagnosis of herpes simplex encephalitis.

Herpes simplex virus encephalitis (HSE) is associated with significant morbidity and mortality both in neonates and adults. An early diagnosis can greatly help to reduce mortality in both groups; however, since none of the presenting symptoms is pathognomonic for HSE, a clinical diagnosis is unreliable. On the other hand, the technique of isolating herpes simplex virus (HSV) from brain biopsies, although providing an early and specific diagnosis, has never been widely accepted because of the risk of neurological complications connected with the invasiveness of the method. In addition, several studies reported that the two HSV types appear to be differently associated with specific neurological complications, indicating that it would be important to gain a differential-type diagnosis to guide both prevention strategies and antiviral therapy. Therefore, the need for noninvasive specific and sensitive techniques has given impulse to the development of assays based on the search of either specific anti-HSV antibodies or viral DNA footprints in patient serum or cerebrospinal fluid. While enzyme-linked immunosorbent assays and immunoblot assays, using HSV type-1- and 2-specific viral glycoproteins, are useful for serological typing, the polymerase chain reaction technique has proved highly effective in giving early, precise and specific HSE diagnosis, thus providing a helpful tool for the identification and treatment of this disease.

Antibodies, Viral↗
PubMed1991

Correlation of early MRI with CT scan, EEG, and CSF: analyses in a case of biopsy-proven herpes simplex encephalitis.

Herpes simplex encephalitis (HSE) carries a high mortality rate. Therefore, an early diagnosis and institution of acyclovir are essential. We report a case of biopsy-proven HSE with 2 negative cerebrospinal fluid (CSF) analyses and 2 normal CT scans. However, MRI together with EEG were abnormal early in the disease stressing their significant role in any suspected case of HSE. Although brain biopsy remains controversial, CSF herpes simplex antigen detection offers hope in providing an early or retrospective diagnosis while specific antiviral therapy with acyclovir is initiated. Overdependency on routine CSF analysis or head CT scan can result in unnecessary delays in diagnosis and treatment.

Acyclovir↗
PubMedDate not supplied

[Kluver Bucy syndrome and central diabetes insipidus: two uncommon complications of herpes simplex encephalitis].

Herpes Simplex Encephalitis (HSE) is an uncommon but severe disease with high mortality and morbidity. The major clinical manifestations are deteriorating consciousness with confusion, drowsiness or coma, altered behaviour, convulsions and a variety of neurological signs (hemiplegia, aphasia, ataxia, etc.). An uncommon complication of HSE is Kluver Bucy syndrome (KBS), characterized by hyperorality, bulimia and changes in emotional behaviour. Neuroimaging studies frequently show an involvement of the temporal lobes and limbic areas. Another uncommon complication of HSE is central diabetes insipidus as a result of herpes simplex infection of the hypothalamus. We report two pediatric cases of HSE complicated with Kluver Bucy syndrome and central diabetes insipidus.

Acyclovir↗