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Routine detection of herpes simplex virus and varicella zoster virus by polymerase chain reaction reveals that initial herpes zoster is frequently misdiagnosed as herpes simplex.

The differential diagnosis of herpes simplex and zoster may require virological confirmation, yet virus typing is not regarded as necessary in routine dermatological assessment. In an attempt to evaluate the clinical benefits of the routine detection of herpes simplex virus (HSV) and varicella zoster virus (VZV), we analysed skin swabs from 110 patients who were diagnosed at the first clinical visit as having herpes simplex (n = 45) or zoster (n = 65). Viruses were typed using the polymerase chain reaction (PCR) with the general primer pair GPHV-RU. PCR analysis showed that at the initial clinical presentation, herpes simplex in these patients was not mistaken for zoster but that zoster was incorrectly diagnosed as herpes simplex in nine cases. Thus these results suggest that initial zoster often mimics herpes simplex, hence routine PCR diagnosis of HSV and VZV or alternative rapid diagnostic approaches may be beneficial in these cases.

Adult↗

Mapping of the herpes simplex virus DNA sequences present in herpes simplex virus type-1 thymidine kinase-transformed cells.

Analyses of the herpes simplex virus (HSV) DNA sequences which are present in three HSV thymidine kinase-transformed (HSVtk+) mouse cell lines have revealed that these cells contain relatively large and variable portions of the viral genome. Two of these cell lines do not contain the viral DNA sequences known to encode the early viral genes normally responsible for regulating tk gene expression during lytic HSV infections. This finding suggests that cell-associated viral tk gene expression may be regulated by cellular rather than viral control mechanisms. In addition, we have compared the viral DNA sequences present in one unstable HSVtk+ cell line to those present in tk- revertant and tk+ rerevertant cell lines sequentially derived from it. Our results have shown that within the limits of sensitivity of our mapping approach, these three related cell lines contain the same set of viral DNA sequences. Thus, gross changes in viral DNA content do not appear to be responsible for the different tk phenotypes of these cells.

Animals↗

Value of serum anti-herpes simplex viral IgM antibody testing in empirical antiviral treatment of herpes simplex encephalitis.

Early antiviral treatment is important for herpes simplex encephalitis. A reliable test for supporting empirical therapy with antiviral agents is urgently needed. Sixty-six children with fever, focal seizures, and consciousness disturbance had their sera examined for anti-herpes simplex viral immunoglobulin M (IgM) antibody with enzyme-linked immunosorbent assay. The result was positive in all seven patients confirmed to have herpes simplex encephalitis. Only two of the other 59 patients were positive on this test. The average period for the development of serologic positivity was 7.3 days from the onset of neurologic symptoms. Although most sera were not tested in the early stage, all were collected on admission day. Our data suggest that before further evidence indicates another diagnosis, this simple, but specific IgM antibody test could be used as a guide for deciding to continue the antiviral treatment for serologically positive cases or to discontinue antiviral treatment for serologically negative ones. Yet, we would not suggest diagnosing herpes simplex encephalitis with this test alone.

Acyclovir↗

Herpes simplex encephalitis: an autopsy case with isolation of type 1 herpes simplex virus.

An adult case of herpes simplex encephalitis was studied after autopsy. Postmortem examination revealed necrotizing encephalitis associated with Cowdry type A intranuclear inclusion bodies in glial cells. Herper simplex virus type 1 was isolated from the removed brain. Herpes simplex virus antigens were detected diffusely in wide areas of the brain by immunofluorescent test and viral particles characteristic to herpes simplex virus were demonstrated by electron microscopy. There was an apparent discrepancy between severity of histological changes and distribution of virus antigen.

Adult↗

[Difficulties in early diagnosis of Herpes simplex encephalitis].

Herpes simplex virus infection of the central nervous system is still a significant cause of morbidity and often mortality at relatively young people. Changes of central nervous system are results of primary infection or activation of latent HSV-1, HSV-2. Neurological deficits often follow encephalitis herpetica. CT, MRI and SPECT are usefull tools in early recognition of herpes encephalitis. The aplication of PCR is prompt and specific diagnosis of herpes simplex virus infections of the brain. Advances in treatment Herpes simplex encephalitis with acyclovir have improved outcome.

Antiviral Agents↗

Herpes simplex virus type 1 that exhibits herpes simplex virus type 2 sensitivity to (E)-5-(2-bromovinyl)-2'-deoxyuridine.

A clinical isolate, designated 145, of herpes simplex virus (HSV) had type 1 characteristics as determined by monoclonal antibody immunofluorescence, heat stability of viral thymidine kinase (TK), BamHI restriction endonuclease pattern, and absence of the HSV-2-specific 38-kD protein. However, instead of being sensitive to E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) like HSV-1, isolate 145 displayed a resistance pattern like HSV-2 to the drug as determined by viral replication and viral DNA synthesis. Because BVDU is activated by viral TK phosphorylation, we cloned the TK-containing DNA region from isolate 145 and compared it by restriction mapping using several endonucleases to similar regions of HSV-1 and HSV-2. In each instance, the patterns for HSV-1 and isolate 145 were identical to each other, but distinct from the patterns for the corresponding region of HSV-2, suggesting that the genome TK region of isolate 145 was HSV-1-like.

Animals↗

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↗

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↗

Operculum syndrome: unusual feature of herpes simplex encephalitis.

Herpes simplex encephalitis in adults and young patients carries a high mortality and morbidity. Its presentation may be nonspecific, sometimes hampering early diagnosis. Two young children are reported with herpes simplex encephalitis in whom the operculum syndrome was an outstanding feature. This syndrome is caused by focal, bilateral cortical damage to the anterior opercular regions resulting in anarthria and impairment of mastication and swallowing. After initiation of treatment with acyclovir in the early stage of the disease, the outcomes in both patients were characterized by good general recovery with persistence of deficits of speech, mastication, and swallowing, more pronounced in the patient who was comatose during the illness. Early recognition of the operculum syndrome as a presenting feature of herpes simplex encephalitis may expedite the diagnosis and thereby improve the prognosis.

Acyclovir↗

Mapping of the herpes simplex virus DNA sequences in three herpes simplex virus thymidine kinase-transformed cell lines.

We have made use of a novel filter hybridization approach in order to map the herpes simplex virus (HSV) DNA sequences which are present in three HSV thymidine kinase (TK)-transformed cell lines. The cell line 33A+ which was produced by infection of 3T3 TK- cells with UV-irradiated HSV-2 (333) was found to contain one contiguous stretch of viral DNA sequences which maps between 0.15 and 0.57 on the HSV-2 genome. The sequences mapping from 0.31 to 0.37 were present in 3--4-fold higher abundance than the rest of the viral DNA sequences in this cell line. Cell lines 5A and 8N were produced by transfection of mouse CL1D cells with sheared HSV-1 (1023) DNA. The cell line 5A was found to contain a contiguous set of viral DNA sequences mapping between 0.26 and 0.41 on the HSV-1 genome. The cell line 8N was found to contain three non-contiguous sets of viral DNA sequences, mapping between 0.09 and 0.41, 0.53 and 0.58, and 0.94 and 1.0 on the HSV-1 genome. These results seem to indicate that many different sets of viral DNA sequences can be incorporated into the cell during HSV-mediated biochemical transformation.

Animals↗

Lymphocyte responses to herpes simplex virus isolates from patients with primary and recurrent herpes simplex genitalis.

The ability of herpes simplex (HSV) isolates from patients with herpes simplex genitalis (HSG) to induce lymphocyte transformation in cells from unrelated, healthy, seropositive donors was examined in a standard lymphocyte transformation assay. All HSV isolates were obtained, before the initiation of therapy, from patients who were enrolled in a placebo-controlled trial of acyclovir in the treatment of HSG. Isolates from patients with primary infections were used, as well as those from patients with frequent (eight or more episodes per year) or infrequent (two or fewer per year) recurrent disease. Blastogenic responses to isolates from patients with infrequent HSG recurrences were significantly less than those to isolates from patients either primary infections or frequent recurrences. No differences between the latter two groups of isolates were seen. These observations demonstrate that differences among naturally occurring HSV isolates exist as determined by this in vitro assay of host-virus interactions. Differences among strains may be important in the pathogenesis of HSV infections, particularly with respect to latency.

Adult↗

Mapping of the structural gene for the herpes simplex virus type 2 counterpart of herpes simplex virus type 1 glycoprotein C and identification of a type 2 mutant which does not express this glycoprotein.

The gene encoding glycoprotein F (gF) of herpes simplex virus type 2 (HSV-2) was mapped to the region of the viral genome from 0.62 to 0.64 map units. This region is colinear with, and partially homologous to, the region of the HSV-1 genome previously shown to encode gC. Mapping of the gF gene was done by insertion of HSV-2 DNA fragments into the thymidine kinase gene of an HSV-1 virus and screening of the resultant recombinant viruses for the expression of gF. In this way, DNA sequences necessary for the expression of gF in infected cells were also delimited. Because several plaque morphology mutants (syncytial mutants) of HSV-1 have previously been shown to be gC-, a syncytial mutant of HSV-2 (GP) was tested for the expression of gF. It was found to be gF-, indicating that gF is not essential for replication of HSV-2 in cell culture, just as gC is not essential for replication of HSV-1. This result also suggests that the gF- and gC- phenotypes are related in the same, as yet undefined, way to the expression of a syncytial marker. A proposal to change the name of HSV-2 gF to gC (gC-2) is discussed.

Animals↗

Detection of type-specific antibody to herpes simplex virus type 1 by radioimmunoassay with herpes simplex virus type 1 glycoprotein C purified with monoclonal antibody.

Herpes simplex virus type 1 (HSV-1) and HSV-2 specify at least four glycoproteins designated gA/gB, gC, gD, and gE. Previous studies have shown that gC produced by HSV-1 is antigenically distinct from the corresponding HSV-2 glycoprotein. With the exception of gC, the glycoproteins of both serotypes share antigenic sites. Standard serological assays fail to differentiate the antibody to the shared antigenic determinants from the type-specific antibody. In this paper, we describe a procedure for purifying gC from HSV-1-infected cell extracts with an immunoadsorbent prepared with an HCL monoclonal antibody. When used in a solid-phase radioimmunoassay, gC proved to be a type-specific antigen for quantitation of antibody to HSV-1. Among individuals who had no antibody to HSV at the onset of infection, all of those with primary HSV-1 infection developed antibody to gC. Subjects with primary HSV-2 infection failed to develop antibody reactive with gC of HSV-1 (P less than 0.01). Both immunoglobulin G and M antibodies against gC were detected in sera from subjects with either primary or recurrent HSV-1 infection. Higher antibody titers to gC were found in sera from individuals with recurrent infection than in sera from those with primary HSV-1 infection.

Antibodies, Monoclonal↗

Management of genital herpes simplex infection.

Herpes simplex infection of the genitals is a common condition, more often due to herpes simplex virus (HSV) type 2 than to type 1 virus. There is a severe first attack followed by mild recurrences which are more common and more frequent after HSV-2 than after HSV-1 genital infection. Clinical features with prodrome, vesicles and erosions may be characteristic allowing rapid clinical diagnosis. When possible laboratory confirmation should be attempted. General management includes simple hygiene, avoidance of sexual transmission, use of condoms, and notifying partners. Oral acyclovir (Zovirax, Wellcome) is the drug of choice for initial attacks and should be considered for all women with this diagnosis. Intravenous acyclovir may be used for very severe attacks. Men with initial attacks may be treated with oral acyclovir but mild disease affecting only skin may be treated with 5% acyclovir cream. Recurrences are short so acyclovir has less effect. Frequent recurrences can be troublesome and may be suppressed by continuous oral acyclovir, or individual attacks may be aborted with intermittent therapy. Various systemic complications may occur; an important but rare problem is primary herpes in late pregnancy. Acyclovir is effective in the treatment of the troublesome herpes simplex disease associated with human immunodeficiency infection. Acyclovir is one of the more expensive treatments for sexually transmitted diseases. At present in many countries costs are being examined, and application of the principles outlined here should help to minimize cost and maximize care.

Acyclovir↗

Infection of human NT2 cells and differentiated NT-neurons with herpes simplex virus and replication-incompetent herpes simplex virus vectors.

The human embryonal carcinoma cell line NT2 differentiates irreversibly into postmitotic neuron-like cells following treatment with retinoic acid. These differentiated NT-neurons resemble central nervous system (CNS) neurons and are characterized by development of dendrites and axons and the expression of neuron-specific markers. Because of their unique biological characteristics, NT-neurons were investigated for their utility as a system for studying the replication of herpes simplex virus (HSV) in the neuron and for evaluating characteristics of HSV vectors designed for gene delivery to the neuron. Virus replication in differentiated NT-neurons was significantly reduced and delayed relative to replication in undifferentiated NT2 cells. Replication of thymidine-kinase (tk) deficient HSV was further impaired in NT-neurons, reflecting the behavior of tk-negative virus in primary neurons in vitro and ganglia in vivo. Furthermore, replication-incompetent HSV vectors were capable of infecting NT-neurons, expressing a foreign gene, and persisting in a recoverable state for at least 2 weeks following delivery. These results suggest that differentiated NT-neurons can provide a continuous source of human, post-mitotic neurons-like cells for the study of HSV biology and HSV vector development.

Cell Differentiation↗

[Herpes simplex encephalitis].

Herpes simplex virus infection of the central nervous system is still a significant cause of morbidity and often mortality. Changes of central nervous system are results of primary infection or activation of latent HSV-1, HSV-2. Neurological deficits often follow encephalitis herpetica. The application of PCR is prompt and specific diagnosis of herpes simplex virus infections of the brain. Advances in treatment herpes simplex encephalitis with acyclovir have improved outcome.

Acyclovir↗

Nutritional requirements for the production of herpes simplex virus. I. Influence of glucose and glutamine of herpes simplex virus production by HeLa cells.

Lewis, Vester J., Jr. (University of Oklahoma School of Medicine, Oklahoma City) and L. Vernon Scott. Nutritional requirements for the production of herpes simplex virus. I. Influence of glucose and glutamine on herpes simplex virus production by HeLa cells. J. Bacteriol. 83:475-482. 1962.-The importance of glucose and glutamine in herpes simplex virus production by HeLa cells was evaluated by variation of the composition of Eagle's basal medium. Simultaneous omission of glucose and glutamine from the serum-containing medium resulted in marked curtailment of viral synthesis. The effect was attributable neither to decreased survival time of infectious particles or of cells, nor to decreased rate of viral adsorption or penetration in the presence of the deficient medium. Therefore, the effect was probably on intracellular viral replication.When the requirements for glucose and glutamine were determined separately, it was found that viral production was reduced in glucose-deficient medium. In contrast, a medium which was complete except for restriction of the glutamine content to that occurring naturally in the serum component supported significantly greater viral multiplication than did the complete medium. Limited viral replication occurred with medium which lacked both glutamine and serum. Viral multiplication in the presence of serum-free medium was stimulated by the addition of glutamine.

Carbohydrate Metabolism↗