On the control of late gene expression in Kaposi's sarcoma-associated herpes simplex virus (human herpes simplex virus-8).

Herpesvirus late genes require viral DNA replication for maximal expression. Although late gene expression appears to require DNA replication in cis in alphaherpes viruses, studies in Epstein-Barr virus (EBV) suggest that this cis-requirement might not pertain to the gammaherpes viruses. Based on these findings, a system was created to investigate the elements required for the regulation of Kaposi's sarcoma-associated herpes simplex virus (KSHV; human herpes simplex virus-8) late gene expression. The transcript of a classic late gene encoding the viral assembly protein was characterized and reporter genes driven by the assembly protein promoter region were constructed. Unlike the EBV case, expression of a reporter gene under the control of the assembly protein promoter did not display authentic regulation when removed from the context of the viral genome. Although reporter expression rose in cells displaying lytic replication, this expression was not diminished by specific inhibitors of viral DNA synthesis. Minimal core promoters were similarly unable to reproduce late gene regulation. These results suggest that proper KSHV late gene expression is likely to be dependent upon virus lytic replication in cis and indicate that the regulation of KSHV late genes more closely resembles that observed in herpes simplex virus than that described for EBV.

Follow-up of pregnant women at high risk of transmitting herpes simplex virus.

Prospects for neonatal herpes simplex transmission were studied in a group of pregnant Chilean women at high herpetic risk--including 59 with a history of Genital Herpes, 11 with a first genital herpes simplex episode during the observed pregnancy, and 16 whose sexual partners had a history of Genital Herpes. Each woman completed a survey questionnaire, provided serologic samples for detection of herpes simplex virus (HSV), and provided periodic samples taken with cotton swabs for HSV isolation. The 86 women who completed the study had an average age of 28 years; most (58.8%) were primiparas. Only 21 of the 86 subjects yielded HSV isolates (predominantly HSV-2) from weekly cotton swab samples taken from the 34th week of pregnancy onward. HSV-2 predominance was found both in the symptomatic cases and in the three asymptomatic ones. Of six subjects found to be shedding HSV at the time of delivery, only one exhibited asymptomatic shedding. These findings are consistent with the following conclusions derived from studies in developed countries: (1) Isolation of HSV in pregnancy does not define a greater risk of shedding HSV during childbirth. (2) In nearly all (five of six) cases, HSV shedding during childbirth involved symptomatic episodes of herpes simplex that clearly defined the steps to be taken by the physician. (3) Despite this, the finding of one asymptomatic case demonstrates that the physician should request a test for HSV isolation at the time of delivery by a woman at high herpetic risk.

Neonatal herpes simplex virus infection in the British Isles.

This study was set up to estimate the incidence of neonatal herpes simplex virus (HSV) infection in the British Isles, and to document the outcome of neonatal infection. Paediatricians reported cases of neonatal HSV through the active reporting scheme of the British Paediatric Association Surveillance Unit. Over a 5 1/2 year period (1986-91) 76 infants with neonatal HSV infection were reported, an incidence of recognised infection in the British Isles of 1.65/100000 livebirths. Twenty-five infants had HSV-1 infection, 24 HSV-2 and in 27 virus type was unknown. Twenty-seven had disseminated infection, 23 herpes simplex encephalitis and 26 localised infection. Nineteen infants (25%) died in the neonatal period, and a further 25 (33%) have subsequently died or have long-term sequelae. At least half of the infants had been discharged home before symptoms became apparent. For 21 women there was evidence of a maternal genital herpes simplex infection at some time, but this was reported or diagnosed retrospectively after neonatal HSV was suspected in 19 cases, and antenatally in only two. Neonatal HSV is rare in the British Isles and routine antenatal screening for genital herpes simplex infection during pregnancy is not justified. A high proportion of infected infants present with non-specific signs and symptoms and without mucocutaneous involvement; furthermore, there is rarely a history of maternal infection. As early diagnosis and prompt treatment is essential, there must be a high level of awareness of the serious nature of neonatal HSV infection.

UL27.5 is a novel gamma2 gene antisense to the herpes simplex virus 1 gene encoding glycoprotein B.

An antibody made against the herpes simplex virus 1 US5 gene predicted to encode glycoprotein J was found to react strongly with two proteins, one with an apparent Mr of 23,000 and mapping in the S component and one with a herpes simplex virus protein with an apparent Mr of 43,000. The antibody also reacted with herpes simplex virus type 2 proteins forming several bands with apparent Mrs ranging from 43,000 to 50,000. Mapping studies based on intertypic recombinants, analyses of deletion mutants, and ultimately, reaction of the antibody with a chimeric protein expressed by in-frame fusion of the glutathione S-transferase gene to an open reading frame antisense to the gene encoding glycoprotein B led to the definitive identification of the new open reading frame, designated UL27.5. Sequence analyses indicate the conservation of a short amino acid sequence common to US5 and UL27.5. The coding sequence of the herpes simplex virus UL27.5 open reading frame is strongly homologous to the sequence encoding the carboxyl terminus of the herpes simplex virus 2 UL27.5 sequence. However, both open reading frames could encode proteins predicted to be significantly larger than the mature UL27.5 proteins accumulating in the infected cells, indicating that these are either processed posttranslationally or synthesized from alternate, nonmethionine-initiating codons. The UL27.5 gene expression is blocked by phosphonoacetate, indicating that it is a gamma2 gene. The product accumulated predominantly in the cytoplasm. UL27.5 is the third open reading frame found to map totally antisense to another gene and suggests that additional genes mapping antisense to known genes may exist.

The significance of herpes simplex for school nurses.

Herpes Simplex is a common recurrent viral infection caused by the herpes simplex virus. The two closely related but distinct viruses that cause herpes simplex infections are herpes simplex 1 (HSV-1) and herpes simplex 2 (HSV-2). HSV-1 is commonly associated with infections around the oral mucosa and is the cause of Herpes Labialis, often referred to as a fever blister or cold sore. HSV-2 infections are usually acquired sexually. Genital herpes simplex is a sexually transmitted disease with the highest prevalence among adolescents and young adults. Knowledge of viral activity, disease management, and community resources will assist the school nurse in developing and implementing strategies to prevent and manage this chronic disease.

High cumulative incidence of genital herpes simplex amongst HIV-1 seropositive heterosexuals in south London.

The cumulative incidence of sexually transmitted diseases (STD) in a cohort of 51 (35 female, 16 male) HIV-1 seropositive STD clinic attenders who had acquired HIV-1 infection via heterosexual transmission was investigated through a retrospective review of the case notes. The women were followed up for a mean 11.6 months and the men for 18 months. Thirty-one (88%) of the women and 13 (81%) of the men were of sub-Saharan African origin. Approximately half of the subjects were first diagnosed as HIV-1 positive with CD4 counts < 200 x 10(6)/1 and a quarter with CD4 counts < 50 x 10(6)/1. STDs detected in women were: genital herpes simplex 15 (43%), candida 12 (34%), bacterial vaginosis 9 (25%), and in men: genital herpes simplex 6 (38%), non-gonococcal urethritis 4 (25%). No cases of gonorrhoea were detected. At the time of first diagnosis of genital herpes simplex at the clinic, the mean CD4 count in women was 275 x 10(6)/1 and in men 285 x 10(6)/1. Genital herpes simplex was the AIDS defining diagnosis in 3 of the women. The recognized risk of HIV transmission via genital lesions should be stressed in HIV-1 positive subjects with Genital Herpes. The incidence of other STD was low--both knowledge of HIV status and safer sex counselling may limit unsafe sexual behaviour and should be evaluated further as a strategy for limiting the spread of HIV-1 infection.

Herpes labialis and genitalis in general medicine

OBJECTIVE: The purpose of this study was to determine the respective importance of Herpes Labialis and genitalis in patients consulting general practitioners and ascertain their knowledge and opinions concerning Herpes Labialis and genitalis in order to analyze patient behavior in case of flare-ups. PATIENTS AND METHOD: A questionnaire was proposed to a representative sample of patients aged 15 years and older seen at consultation by 49 general practitioners participating in the General Medicine Observatory of the French Society of General Practitioners. RESULTS: Among the 4,403 patients who responded, a known history of Herpes Labialis was reported by 39. 9 p.100 and of herpes simplex genitalis by 2.5 p.100. Their answers to the questions demonstrated insufficient knowledge of avoidable risks of herpes simplex as a sexually transmitted disease, with very significant misunderstanding by men. Among the 1,711 patients who had experienced Herpes Labialis, 62.9 p.100 initiated self-medication, 29 p.100 preferred to wait and see and 7.5 p.100 sought medical assistance. Among the 108 patients who had experienced herpes simplex genitalis, at the last flare-up 40 p.100 initiated self-medication, 7.5 p.100 preferred to wait and see and 52 p.100 sought medical assistance. The general practitioner was the first physician consulted for both types of herpes. DISCUSSION: This study illustrates the importance of herpes simplex infections in the general medicine patients. It also confirms that new interventional strategies are needed both for health care and for health education.

Cell surface heparan sulfate is a receptor for human herpes simplex virus 8 and interacts with envelope glycoprotein K8.1.

An immunodominant envelope glycoprotein is encoded by the human herpes simplex virus 8 (HHV-8) (also termed Kaposi's sarcoma-associated herpes simplex virus) K8.1 gene. The functional role of glycoprotein K8.1 is unknown, and recognizable sequence homology to K8.1 is not detectable in the genomes of most other closely related gammaherpes viruses, such as herpes simplex virus saimiri or Epstein-Barr virus. In search for a possible function for K8.1, we expressed the ectodomain of K8.1 fused to the Fc part of human immunoglobulin G1 (K8.1DeltaTMFc). K8.1DeltaTMFc specifically bound to the surface of cells expressing glycosaminoglycans but not to mutant cell lines negative for the expression of heparan sulfate proteoglycans. Binding of K8.1DeltaTMFc to mammalian cells could be blocked by heparin. Interestingly, the infection of primary human endothelial cells by HHV-8 could also be blocked by similar concentrations of heparin. The specificity and affinity of these interactions were then determined by surface plasmon resonance measurements using immobilized heparin and soluble K8.1. This revealed that K8.1 binds to heparin with an affinity comparable to that of glycoproteins B and C of herpes simplex virus, which are known to be involved in target cell recognition by binding to cell surface proteoglycans, especially heparan sulfate. We conclude that cell surface glycosaminoglycans play a crucial role in HHV-8 target cell recognition and that HHV-8 envelope protein K8.1 is at least one of the proteins involved.

Effects of topical unoprostone and latanoprost on acute and recurrent herpetic keratitis in the rabbit.

PURPOSE: To determine the effect of the topical ocular hypotensive drug, isopropyl unoprostone, a docosanoid molecule with very weak prostaglandin activity, on herpes simplex keratitis in the rabbit eye. METHODS: For acute disease, rabbit corneas inoculated with the corticosteroid-sensitive F(MP)E strain of herpes simplex virus type 1 were treated with various combinations of 0.12% isopropyl unoprostone, latanoprost, trifluridine, benzalkonium chloride 0.02%, dexamethasone sodium phosphate, ketorolac tromethamine, or saline solution beginning 1 day after infection. Severity of keratitis was evaluated in a masked manner. For recurrent disease, rabbit corneas infected with McKrae strain herpes simplex virus type 1 were treated with unoprostone or saline solution on postinfection days 25 to 42, and the presence or absence of lesions was recorded. RESULTS: Eyes treated with unoprostone showed significantly less severe disease than saline-treated or latanoprost-treated eyes during acute infection. Unoprostone-treated and saline-treated eyes showed no significant difference in the frequency of recurrent lesions. Eyes treated with latanoprost and/or dexamethasone, separately or in combination, showed increased severity of acute herpes simplex virus keratitis, whereas benzalkonium chloride 0.02%--treated eyes showed no significant difference, compared with saline treatment. Trifluridine resulted in rapid healing. CONCLUSIONS: Unoprostone did not increase the severity or recurrence rate of herpes simplex virus keratitis. Unoprostone requires twice-a-day administration, compared with once-a-day for latanoprost, and unoprostone lowers intraocular pressure less than latanoprost. Nevertheless, unoprostone's superior safety profile may make its use advantageous. Benzalkonium chloride alone did not make the keratitis worse.

Detection of varicella-zoster virus (VZV) DNA in throat swabs and peripheral blood mononuclear cells of immunocompromised patients with herpes zoster by polymerase chain reaction.

BACKGROUND: Varicella-zoster virus (VZV) is rarely isolated from throat swabs and peripheral blood leukocytes from patients with herpes zoster by conventional virus isolation methods. The polymerase chain reaction (PCR) is a highly sensitive method to detect VZV genomes. It has been reported that VZV DNA was detected in the cerebrospinal fluid (Puchhammerstockl et al., 1991) and peripheral blood mononuclear cells (PBMC) of patients with VZV-associated neurological symptoms (Gilden et al., 1992) by PCR. OBJECTIVES: We used the nested double PCR to detect VZV DNA in patients with herpes zoster. STUDY DESIGN: Sixteen patients with herpes zoster, ten immunocompromised and six immunocompetent patients, were studied. Throat swabs and PBMC were collected weekly and examined for VZV DNA by the nested double PCR. RESULTS: VZV DNA was detected in 60% (6/10) of throat swabs and in 60% (6/10) of PBMC of immunocompromised patients, and in 16.7% (1/6) of throat swabs and in 33% (2/6) of PBMC of immunocompetent patients within two weeks after the onset of skin rash. VZV DNA was detected in throat swabs or PBMC of two patients 5 and 7 days after cessation of Acyclovir. CONCLUSION: VZV DNA was detected in throat swabs and PBMC-associated viremia exist in patients with herpes zoster. It is suggested that VZV spread from sensory ganglia to the skin or pharyngeal area along the nerve fiber or hematogenously and local cutaneous replication of VZV can lead to viremia with subsequent hematogenous dissemination in patients with herpes zoster.