SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
BACKGROUND: Herpes simplex encephalitis is one of the most common and serious sporadic encephalitides of immunocompetent adults. Herpes simplex virus 2 (HSV-2) infections of the central nervous system usually manifest as subacute encephalitis, recurrent meningitis, myelitis, and forms resembling psychiatric syndromes. OBJECTIVES: To report and discuss magnetic resonance imaging (MRI) findings and clinical features in atypical brainstem encephalitis and facial palsy associated with HSV-2. SETTING: Neurology department of a tertiary referral center. PATIENT: A 37-year-old woman was admitted to the hospital with fever, diplopia, left hemiparesis, sensory change in the face and limbs, personality changes, frontal dysexecutive syndrome, and a stiff neck. Brain MRI showed multifocal high-signal intensities in the pons, midbrain, and frontal lobe white matter on T2-weighted and fluid-attenuated inversion recovery images. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) amplification analysis was positive for HSV-2. Acyclovir therapy was started, and the encephalitic symptoms disappeared with a negative conversion of HSV-2 PCR in the CSF. However, after the discontinuation of acyclovir therapy, peripheral facial palsy occurred on the left side. A possible relapse or delayed manifestation of the HSV-2 infection was suspected, and the acyclovir therapy was restarted. A complete remission was achieved 3 days after the treatment. She was discharged without any neurologic sequelae. CONCLUSIONS: We describe a patient who developed atypical encephalitis due to HSV-2 and peripheral facial palsy, which could also be related to the HSV-2. This case suggests that HSV-2 should be considered among the possible causes of atypical or brainstem encephalitis and that the PCR amplification method of the CSF can help reveal the possible cause of HSV-2.
Genital herpes simplex virus infections should be classified into first-episode and recurrent infections. First-episode infections include true primary infections in patients with seronegative results who have never been infected with any type of herpes and nonprimary first-episode infections in patients who have been infected before and have serum antibody and humoral immunity, an example being genital infection with type 2 in adolescence after orolabial infection with type 1 in childhood. First-episode infections show more extensive disease, more systemic symptoms, and greater viral shedding than do recurrent infections. Ten percent to 15% of patients with first-episode primary genital herpes have oropharyngeal infections with the same virus strain. Herpesvirus can be isolated from the urethra in about 30% of male patients with first-episode infections. In recurrent vulvar herpes, virus can be isolated from the cervix in 10% to 15% of patients. Many genital lesions that clinically suggest something else turn out to be herpes; herpes may be diagnosed 5% of the time clinically but cultures are positive 14% of the time. Primary genital herpes type 2 infections recur about 95% of the time whereas type 1 infections recur about 50% of the time. Recurrences are highly unpredictable from patient to patient and time to time. The role of asymptomatic shedding in the spread of herpes is a major area for future study. Antiviral treatment is probably going to change the epidemiology of herpetic infections very little.
BACKGROUND: Herpes simplex virus (HSV) can cause postpartum endometritis. The clinical diagnosis of HSV endometritis has been reported previously. The disease is responsive to acyclovir intravenously. CASE: A 22-year-old woman, gravida 2, para 1, status post primary cesarean section for a double footling breech presentation, developed a persistent postpartum fever. Simulating the febrile course of septic pelvic thrombophlebitis, the patient's condition was unresponsive to broad-spectrum antimicrobials and heparin therapy. Active herpetic lesions and a positive cervical culture for herpes simplex prompted the use of intravenous acyclovir. Rapid resolution of the fever and the similarity to previous case reports suggested the clinical diagnosis of herpes simplex endometritis. CONCLUSION: The diagnosis of postpartum herpes simplex endometritis should be considered when managing a persistent postpartum fever unresponsive to aggressive antimicrobial and heparin therapy. Immediate resolution of the fever should occur with the use of acyclovir.
Neonatal herpes is a potentially devastating consequence of perinatal transmission of the herpes simplex virus (HSV), with significant morbidity and mortality. Treatment options are available, but must begin early in disease with manifestations that are often protean. Thus, preventive measures need to be optimised. Antiviral suppression in late pregnancy of women with a history of recurrent genital herpes will decrease symptomatic recurrence at delivery and appears to reduce caesarian section rates. However, primary HSV Type 2 and primary HSV Type 1 episodes have the highest neonatal transmission rates and thus, effective prevention may require the identification and suppression of the discordant partner. Significant experience has been gained with the use of acyclovir in pregnancy and it is recommended for both episodic and suppressive therapy in pregnant women. Its use has been demonstrated to be cost-effective in suppressive therapy, although issues regarding compliance and the potential for neonatal neutropenia need to be addressed. The more conveniently dosed prodrugs valacyclovir and famciclovir are being evaluated for use in pregnancy.
Herpes simplex virus (HSV) is a common sexually transmitted infection (STI) worldwide, and the prevalence of this infection has increased significantly over the last two decades in many developed countries. The objective of educational interventions is to limit HSV transmission. There are few data on the effectiveness of such interventions but much of the published data, from the UK and the USA, suggest that they may be beneficial. In the USA, Project RESPECT demonstrated that counselling those at risk may reduce HSV acquisition, a conclusion supported by data from candidate HSV vaccine trials and educational initiatives for other STIs. Patients should be counselled on the natural history of genital HSV infection, variability in recurrence and strategies to limit transmission risk, using measures such as promoting condom use and limiting the number of sexual partners. Healthcare providers should give consistent, relevant information and know where patients can access further information. Serological testing may allow an opportunity to counsel patients about genital herpes. A significant barrier to effective implementation of educational interventions is the low level of accurate knowledge among the general public regarding genital herpes, especially about asymptomatic shedding, transmission, risk reduction strategies and therapeutic options. Often there is no link between knowledge and behaviour, with success potentially depending on the character of the patients. Due to the lack of knowledge, mass education campaigns may be required, although targeted campaigns may provide a more cost-effective solution. These campaigns should target young adults who have the highest rate of HSV acquisition. Education should also be available to pregnant women, who are likely to be highly motivated to avoid acquisition from infected partners due to the possibility of neonatal herpes.
Recurrent herpes simplex labialis is associated with mild morbidity, but remains a significant problem for people with frequent and/or severe recurrences. Both topical and peroral episodic antiviral treatments of recurrences are modestly effective at reducing the duration of signs and symptoms. Recent studies with high-dose, short-course valaciclovir suggest that maximum benefit from antiviral therapy may be achieved with as little as 1 day of treatment. Topical steroids may be useful in combination with an antiviral agent, but more needs to be learnt about the appropriate strength and duration of steroid therapy before a general recommendation can be made. Selected subgroups of patients are candidates for prophylactic treatment with perorally administered nucleoside antiviral agents. Prophylaxis with topical agents is not effective.
Two herpes simplex type 1 (HSV-1) recombinant viruses carrying the hepatitis C virus (HCV) NS5A open reading frame under the control of the cytomegalovirus immediate early (IE) or a herpes simplex chimeric promoter (alpha 4 gamma 1UL19) were constructed and characterized. Expression studies showed that both HSV-NS5A recombinant viruses were able to express high levels of the NS5A protein in infected cells. Most importantly, using this system, we demonstrated that the NS5A protein interacts with the growth receptor-bound protein 2 (Grb2) and inhibits the phosphorylation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in HeLa, NIH3T3 or liver infected cells. Thus, our studies confirm the ability of the NS5A protein to perturb the extracellular signal-regulated kinase (ERK) pathway in HeLa cells by the use of an alternative system for NS5A expression and extend this observation to additional cell lines. We conclude that HSV-based viral vectors may provide a useful system for studying the expression and selected functional properties of the HCV NS5A protein.
Herpes simplex virus type 1 (HSV1) and type 2 (HSV2) polypeptides with type-common and type-unique epitopes were identified using cross-adsorbed hyperimmune rabbit sera and Western blotting techniques. Twelve HSV1 and fourteen HSV2 polypeptides with type-specific epitopes were identified. Cross-adsorbed human sera reacted to a subset of the type-specific epitopes defined by rabbit sera. Human sera with both HSV1- and HSV2-specific antibodies were identified by their reaction to HSV1-type-specific epitopes after adsorption with HSV2, and HSV2-type-specific epitopes after adsorption with HSV1. Mixing experiments demonstrated the sensitivity of this assay for detecting HSV2-type-specific antibody in the presence of HSV1 antibody. This technique has proven useful in the study of immune response to individual HSV polypeptides during human HSV infections, while the presence of these type-unique epitopes on HSV polypeptides allows for the detection of type-specific antibodies in human sera.
Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite the availability of animal models for HSV-2 infection, little is known regarding the mechanism of immune induction within the vaginal mucosa. Here, we examined the cell types responsible for the initiation of protective Th1 immunity to HSV-2. Intravaginal inoculation of HSV-2 led to a rapid recruitment of submucosal dendritic cells (DCs) to the infected epithelium. Subsequently, CD11c(+) DCs harboring viral peptides in the context of MHC class II molecules emerged in the draining lymph nodes and were found to be responsible for the stimulation of IFNgamma secretion from HSV-specific CD4(+) T cells. Other antigen-presenting cells including B cells and macrophages did not present viral peptides to T cells in the draining lymph nodes. Next, we assessed the relative contribution to immune generation by the Langerhans cells in the vaginal epithelium, the submucosal CD11b(+) DCs, and the CD8alpha(+) lymph node DCs. Analysis of these DC populations from the draining lymph nodes revealed that only the CD11b(+) submucosal DCs, but not Langerhans cell-derived or CD8alpha(+) DCs, presented viral antigens to CD4(+) T cells and induced IFNgamma secretion. These results demonstrate a previously unanticipated role for submucosal DCs in the generation of protective Th1 immune responses to HSV-2 in the vaginal mucosa, and suggest their importance in immunity to other sexually transmitted diseases.
Herpes simplex viruses infect a variety of cells in vitro. However, not all infected cells sustain a fully productive replication of these viruses. We have shown that, in U937 monocytoid cells, herpes simplex virus 2 (HSV-2) causes a low-productive infection characterized by apoptosis as cytopathic effect at a late stage of infection. This effect was associated with a down-regulation of the Bcl-2 protein. We therefore asked whether destabilization of Bcl-2 expression could act as a limiting factor for the productive HSV-2 infection. We found that overexpression of Bcl-2 in U937 cells dramatically increased the capability of these cells to sustain a fully productive infection, while protecting against apoptosis induced by HSV-2. Overall, our data indicate that Bcl-2 expression acts as a regulator of HSV-2 replication.
Herpes simplex virus (HSV) DNA sediments homogeneously on a neutral sucrose gradient but heterogeneously on an alkaline sucrose gradient. Several factors that may influence the alkaline sedimentation pattern of HSV DNA were examined: e.g., the host cell, cell density at time of infection, multiplicity of infection, and the starting material for HSV DNA purification (whether HSV-infected cells or cell-free virus). Based on alkaline sedimentation analysis, these factors appear to play little or no role in the amount of intact single-stranded HSV DNA observed.
Recurrent herpes simplex virus (HSV) encephalitis is a rare disorder with only a few cases reported. We report a case of HSV encephalitis with documented recurrence in the same anatomic location, lending support to the theory of reactivation as the mechanism of disease.
Herpes simplex virus (HSV) infections are common and produce not only a primary infection, but also latent and recurrent infections. Therefore, the goals of a HSV vaccine are different from other vaccines. In this review, the goals of both prophylactic and therapeutic HSV vaccines are discussed and related to the immunobiology of acute and recurrent HSV infections. Next, the vaccine strategies that have been and are being evaluated for control of HSV disease are described. Current approaches take advantage of many of the modern methodologies for vaccine development. Thus, as we await final evaluations of subunit HSV glycoprotein vaccines, early phase I trails are evaluating newer vaccine approaches including DNA-based vaccines and replication-impaired viruses. The definitive HSV vaccine may await increased knowledge of the optimal viral antigen(s) and routes to induce genital tract immunity.
Herpes simplex keratitis (HSK) remains a common cause of unilateral corneal disease. Despite intense research over three decades, the mainstay of therapy continues to be topical and, more recently, systemic acyclovir plus topical corticosteroid in some cases. There is increasing recognition that HSK after keratoplasty can occur not only as a result of recurrence in patients with HSK, but also in patients with other primary diagnoses as a result of activation of HSV in the host, or by transmission of virus in the donor tissue.
BACKGROUND: Herpes simplex virus (HSV-1) stromal keratitis is an immune-mediated disease. Recently, it has been shown that infection of cells with HSV-1 induces apoptosis. In this study we investigated the presence of apoptotic cell death in keratectomy specimens from patients with HSV-1 stromal keratitis. PATIENTS AND METHODS: Keratectomy specimens from six patients with HSV-1 non-necrotizing stromal keratitis were chosen and compared to healthy corneas. Paraffin sections were analyzed histologically and cryosections were studied by the immunoperoxidase technique for the presence of HSV-1, Fas and FasLigand (FasL) antigens. Apoptosis was assessed by TUNEL assay (TdT-mediated dUTP nick-end labeling). RESULTS: In healthy corneas, Fas was detected in the epithelium, keratocytes and endothelium; FasL was present in the epithelium and endothelium; TUNEL-positive cells were only found in the superficial epithelial cells. In contrast, inflammatory cells and scars were found in all HSV-diseased corneas; HSV-1 antigen was detected in only one specimen. Cells within inflammatory infiltrations and epithelium were apoptotic. Fas was detected in all corneal cell layers and inflammatory cells. FasL was restricted to areas of inflammation. CONCLUSIONS: The data suggest that apoptosis plays a role in the pathogenesis of HSV keratitis. The Fas-FasL system appears to be involved in the induction of apoptosis. Apoptosis could be involved in the depletion of inflammatory cells in the cornea and may limit the extension of viral replication to the eye.
Herpes simplex virus 1 (HSV-1) infection induces transcription of the chloramphenicol acetyltransferase (CAT) gene directed by the long terminal repeat (LTR) of human immunodeficiency virus (HIV) in both transiently and permanently transfected cells containing the HIV-LTR/CAT hybrid gene. To define the mechanism by which HSV-1 stimulates the HIV LTR, we examined the effects of isolated regulatory genes from HSV-1. The results of cotransfection assays with the immediate-early (IE) genes of HSV-1, IE110 (ICP0) and IE175 (ICP4), showed that the IE110 protein, either alone or in combination with the IE175 protein, can activate the HIV LTR. Cotransfection with the IE175 gene alone or with the Vmw65 gene (coding for a virion transcription factor) alone did not lead to HIV-LTR activation. The lack of requirement for the IE175 or Vmw65 gene products in transient-expression assays was confirmed in permanent cell lines containing the HIV-LTR/CAT hybrid gene by using temperature-sensitive mutants defective in the IE175 gene product or in uncoating functions. By deletion analysis, we localized a 73-bp-long region (positions -104 to -32) from the HIV LTR that responded to HSV-1 activation; when this region, which is distinct from the previously identified trans-activating responsive (TAR) region, was ligated to a heterologous, HSV-1-nonresponsive gene (alpha 4-interferon/CAT), it conferred inducibility by both HSV-1 infection and IE110/175 cotransfection. Both simian and human cytomegalovirus also induced the HIV-LTR/CAT hybrid gene. However, we failed to detect specific upstream sequence requirements for induction by cytomegalovirus. Our results indicate that infection with unrelated viruses can alter the expression of HIV in an infected cell.
Herpes simplex virus 1 encodes a protein that binds specifically to a viral DNA replication origin (oriS). This origin-binding protein has been purified to homogeneity by means of sequence-specific DNA affinity chromatography. The purified origin-binding protein, which has a molecular weight of 83,000, interacts with both parts of the oriS dyad; however, the affinity for the two sites differs by an order of magnitude. The sequence TTCGCA occurs as a nearly perfect direct repeat within the two sites and may constitute the recognition sequence for the origin-binding protein.