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The equine herpes virus 4 thymidine kinase is a better suicide gene than the human herpes virus 1 thymidine kinase.

The herpes simplex virus type 1 thymidine kinase suicide gene (HSV1tk) together with ganciclovir (GCV) have been successfully used for in vivo treatment of various experimental tumors, and many clinical trials using this system have been launched. With the aim to improve this therapeutic system, we compared the potential efficacy of different herpes virus derived thymidine kinases (HSV1, varicella-zoster virus, equine herpes virus type-4 and Epstein-Barr virus) as suicide genes in association with the nucleoside analogs acyclovir, ganciclovir and bromovinyldeoxyur- idine. Using various murine and human cell lines expressing these viral tk, we show that HSV1- and EHV4tk are the more efficient suicide genes for the different nucleoside analogs tested. Moreover, EHV4tk expressing murine and human cells were three- to 12-fold more sensitive to GCV than HSV1tk expressing cells. This was correlated with the presence of five-fold higher amounts of the toxic triphosphated-GCV in EHV4- versus HSV1tk expressing cells. Altogether, these experiments underline the potential advantages of the EHV4tk as a suicide gene.

Animals↗

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↗

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↗

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↗

Herpes simplex virus specific secretory IgA in lacrimal fluid during herpes keratitis.

The correct diagnosis of herpes keratitis is very important, as the clinical manifestation can be similar to that caused by immunologic defects. The presence of herpes simplex virus (HSV) specified IgG in lacrimal fluid is not of diagnostic value in cases where the eyes are severely inflamed, because the inflammation leads to impairment of the blood vessels and allows a passive diffusion of IgG from serum into the lacrimal fluid. In the present study we have developed a method for the detection of locally produced HSV-specific antibodies of the secretory IgA class present in lacrimal fluid from patients with active herpes keratitis.

Antibodies, Viral↗

Viral folliculitis. Atypical presentations of herpes simplex, herpes zoster, and molluscum contagiosum.

BACKGROUND: Viral folliculitis is an infrequently reported entity. The patients described herein were seen over a 12-year period of practice in a referral dermatologic setting. The cases involve a variety of viral infections limited to the hair follicle. OBSERVATIONS: We describe 5 patients with a variety of viral folliculitides: 2 with herpetic sycosis caused by herpes simplex; 1 with herpex simplex folliculitis (this patient also had human immunodeficiency virus); 1 with herpes zoster without blisters; and 1 with molluscum contagiosum. CONCLUSIONS: These 5 cases demonstrate that viral folliculitis has varied causes and presentations. Clinicians should consider viral agents in the differential diagnosis of superficial infectious folliculitis, especially in cases that are refractory to antibacterial or antifungal therapy.

Adult↗

Double blind trial in the treatment of herpes simplex and herpes zoster with adenine arabinoside and idoxuridine.

In a double blind trial adenine arabinoside (Vidarabine) and Idoxuridine (IDU) were tested in herpes simplex and herpes zoster infections. Adenine arabinoside covered 19 patients with HSV and 6 with HZ while IDU 19 with HSV and 6 with HZ. From the statistical analysis it was found that Vidarabine acts shorter than IDU in HSV P less than 0.01, while in HZ no significant difference P less than 0.5 was found, possibly due to the small number of patients tested.

Adolescent↗

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↗

Detection of herpes simplex virus type 1, herpes simplex virus type 2 and varicella-zoster virus in skin lesions. Comparison of real-time PCR, nested PCR and virus isolation.

BACKGROUND: Herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and varicella-zoster virus (VZV) cause a wide range of signs and symptoms, varying from trivial mucocutaneous lesions to life-threatening infections, especially in immuno-suppressed patients. Since antiviral drugs are available, rapid and sensitive laboratory diagnosis of these virus infections is important. OBJECTIVE: To set up and evaluate HSV-1, HSV-2 and VZV qualitative real-time PCR on the Lightcycler system and to compare the results with those of the 'in-house' nested PCR and virus isolation. STUDY DESIGN: 110 consecutive samples from dermal or genital lesions from patients suspected of having HSV infections and another 110 samples from patients with suspected VZV infections were tested with real-time PCR, nested PCR and virus isolation. RESULTS: 24 samples (22%) were positive for HSV-1 by virus isolation and nested PCR, whereas 26 (24%) were positive by real-time PCR. HSV-2 was detected in 28 samples (25%) by virus isolation, in 41 (37%) by nested PCR and in 40 (36%) by real-time PCR. VZV was isolated in 15 samples (14%) and VZV DNA was detected in 51 samples (46%) by nested PCR as well as by real-time PCR. Nucleic acid amplification increased the detection rate of HSV-2 and VZV DNA in particular compared to virus isolation. No significant difference in sensitivity was found between real-time PCR and nested PCR. CONCLUSION: Real-time PCR has the advantage of rapid amplification, a reduced risk for contamination and it is a suitable method for diagnosis of VZV and HSV in specimens from skin lesions.

Chickenpox↗

Effect of herbal therapy on herpes labialis and herpes genitalis.

Administration of hot water extracts of six herbs to four patients with recurrent herpes labialis led to prompt crusting over and complete recovery within a few days. Similar treatment for one female patient who had been suffering from recurrent genital herpes resolved the associated pain dramatically. In all cases mentioned, symptoms disappeared much more quickly than with previous outbreaks when herb extracts were not administered.

Adult↗

Herpes simplex and herpes genitalis viruses in etiology of some human cancers.

The results of complement fixation tests on 202 sera from people without cancer and from patients with cancer in 29 different areas of the body indicated that only those with nine varieties of advanced cancer (lip, mouth, oropharynx, nasopharynx, kidney, urinary bladder, prostate, cervix uteri, and vulva-all of 56 tested) gave positive specific reactions with nonvirion antigens induced by the DNA herpes simplex (HSV 1) and herpes genitalis (HSV 2) viruses. None of 57 people without cancer (including 10 with current and 18 with recurrent HSV 1 or HSV 2 infections), none of 81 patients with 20 other varieties of advanced cancer (gum, tongue, tonsil, salivary gland, accessory sinus, epiglottis, lung-bronchus, stomach, colon, breast, corpus uteri, ovary, testis, liver, thyroid, Wilms' embryonal kidney, melanoma, Hodgkin's disease, acute lymphocytic leukemia, and acute myelocytic leukemia), and none of four women with early malignant changes in the cervix uteri gave positive results. The seven patients with advanced cancer of the lip or oropharynx gave positive reactions with HSV 1 but not with HSV 2 nonvirion antigens (compatible with involvement of only HSV 1), all of the 13 women with advanced cancer of the cervix uteri and the one woman with advanced cancer of the vulva gave positive reactions with both HSV 1 and HSV 2 nonvirion antigens (compatible with involvement of only HSV 2), while among the 35 other positive patients only two (one with cancer of the kidney and one with cancer of the bladder) reacted with HSV 1 and not at all with HSV 2 nonvirion antigens. Positive sera failed to react with cells harvested at different times after high-multiplicity infection with the DNA vaccinia virus. Massive absorption of positive sera with trypsinized, uninfected human embryonic kidney cells failed to remove, or lower the titer of, the HSV 1 and HSV 2 nonvirion antibodies. All of these data taken together are interpreted as indicating that HSV 1 and HSV 2 play an etiologic role in certain human cancers, because they provide the kind of evidence by which virus-free experimental cancers can be proved to have been originally induced by such DNA viruses as polyoma, Simian Virus 40, or certain types of adenovirus.

Antibodies, Viral↗

Double-blind, placebo-controlled trial of a herpes simplex virus type 2 glycoprotein vaccine in persons at high risk for genital herpes infection.

To determine the efficacy of a herpes simplex virus type 2 (HSV-2) glycoprotein subunit vaccine, vaccine (50 micrograms) or placebo was administered intramuscularly at weeks 0, 4, and 22 to 161 persons who lacked HSV-2 antibodies and were sex partners of persons with recurrent genital herpes. The annual rate of acquisition of HSV infection was similar among vaccine and placebo recipients (10.7% and 8%, respectively) but was higher in initially seronegative subjects (15.5%) than in those with HSV-1 at entry (5.9%). Eleven (79%) of the 14 HSV infections acquired during follow-up were symptomatic. Vaccination elicited ELISA antibody titers to glycoproteins gD2 and gB2 that were only 10% and 5%, respectively, of titers found in persons with recurrent genital HSV-2 infection. This vaccine failed to provide protection from acquisition of genital HSV infection. The lack of efficacy appears to be related, in part, to the poor immunogenicity of the vaccine.

Adult↗

Neonatal herpes simplex virus infection presenting as acute liver failure: prevalent role of herpes simplex virus type I.

BACKGROUND: Acute liver failure (ALF) in neonates is rare but carries a high mortality without liver transplantation. Herpes simplex virus (HSV) is one of the microbes that more commonly causes ALF and is potentially treatable; hence, early diagnosis and treatment are important to avoid progression to liver failure. PATIENTS AND RESULTS: We have analysed retrospectively the case notes of 11 patients with HSV-induced ALF. A history of possible herpes infection was elicited in 5 parents, but HSV had not been suspected clinically. All patients were asymptomatic when discharged from postnatal units and were presented with nonspecific symptoms of poor feeding and lethargy within 2 weeks from birth. Seven of the 11 patients had HSV-1 infection, 4 HSV-2. Only 2 patients who received early treatment with intravenous acyclovir survived. CONCLUSIONS: HSV-related ALF in the neonatal period carries high morbidity and mortality and needs a high index of suspicion so that life-saving treatment can be started promptly. Both HSV-1 and HSV-2 can cause severe neonatal infection. It is important to recognise HSV infection in women of childbearing age and their sexual partners.

Acyclovir↗

Production of specific antibodies by cerebrospinal fluid lymphocytes in patients with herpes zoster, mumps meningitis and herpes simplex virus encephalitis.

We applied a new method consisting of short-term culture (18 h) of lymphocytes from cerebrospinal fluid (CSF-L) and peripheral blood (PBL) in viral antigen-coated ELISA plates and subsequent measurement of IgG and IgM antibodies bound to antigen. Utilizing mumps virus, herpes simplex virus (HSV), varicella zoster virus (VZV), and measles virus as antigens, we demonstrated production by CSF-L of antibodies against the aetiological agent only in all patients with mumps meningitis and HSV encephalitis and also in all patients with herpes zoster without central nervous system (CNS) symptoms. This might be considered as direct evidence that specific antibodies are produced within the CNS in inflammatory nervous system diseases. CSF-L usually produced higher amounts of antibodies than the corresponding number of PBL. In comparison with concentrations of free antibodies determined in parallel, our method had higher specificity and sensitivity and gave more precise information about the antibody response in infections of the nervous system.

Antibodies, Viral↗

The use of betadine antiseptic paint in the treatment of Herpes simplex and Herpes Zoster.

Twenty-two patients with Herpes Simplex were treated with Betadine (povidone iodine) Antiseptic paint and seven with 5% idoxuridine in dimethyl sulphoxide, also one patient with bilateral lesions was treated with the two solutions, one on each side. The povidone iodine alcohol solution appeared to be at least as effective as the idoxuridine with minimal side-effects (some stinging in two patients). Good results were also obtained with this solution in twelve patients with Herpes Zoster.

Adolescent↗

Multicentre clinical trial with herpes simplex virus vaccine in recurrent herpes infection.

The aim of this work was to confirm our preliminary clinical and immunological evaluation of the protective effects of a herpes simplex virus (HSV) vaccine derived from killed virus in the treatment of relapsing facial or genital herpes simplex infection. A total of 142 patients were treated with the HSV vaccine and a control group of 50 were treated with intermittent oral acyclovir (ACV). The vaccine reduced annual active disease days in vaccinees to 11.59 (+/- 15.3) after treatment (65.11 +/- 31.64 before treatment) compared to 30.4 +/- 17.49 days after treatment of the control group patients (71.86 +/- 32.5 before treatment).

Acyclovir↗

[Indices of the immune status of recurrent herpes patients being treated with a herpes polyvaccine].

Patients with dermal and genital forms of recurring herpes were found to have decreased levels of leukocytes and changed balance of the peripheral blood lymphocyte populations. Treatment with herpes inactivated cultural polyvaccine produced a therapeutic effect in a significant number of patients which was accompanied by a correcting effect of the vaccine on their immune status.

Adult↗

[Herpes simplex and herpes varicella-zoster. Cytological and ultrastructural study].

Nuclear staining qualities, and cell morphology depart from normal when epithelial cells are infected by herpes virus hominis and herpes varicella-zoster (1). The cytopathic changes produced by both viruses are similar and constant enough to be considered characteristic of the infection. Since the skin vesicles are readily accessible for examination, it is easy to scrape infected cells from the floor of the exposed blister and establish the diagnosis. The simplest and most common method would be by light microscopy utilizing conventional staining. When the circumstances warrant it and the facilities are available, the virus itself can be demonstrated by electron microscopy with material obtained in the same fashion. This paper deals with two cases in which the initial diagnosis of the disease was made by cytologic examination and the presence of virus subsequently verified by electron microscopy.

Cytopathogenic Effect, Viral↗