Primary Herpes Simplex Research Articles

Novel Mouse Model of Recurrent Sublethal Herpes Simplex Virus Infection Recapitulates Human Antibody Responses to Primary and Chronic Infection.

Background: Herpes simplex virus (HSV) vaccine development has been impeded by the absence of predictive preclinical models and defined correlates of immune protection. Prior candidates elicited neutralizing responses greater than natural infection but no antibody-dependent cellular cytotoxicity (ADCC) and failed to protect in clinical trials. Primary HSV infection also elicits only neutralizing responses, but ADCC and an expanded antigenic repertoire emerge over time. This evolution may contribute to the decreased frequency and severity of recurrences. To test this notion, we developed a recurrent HSV infection mouse model and evaluated changes in humoral immunity with repeated challenges. Methods: Mice were repeatedly infected intranasally with clinical isolates of HSV-1 or HSV-2 for four months. HSV binding IgG, neutralizing (with or without complement) and ADCC-mediating antibodies were quantified prior to each round of infection. Viral targets were assessed by western blotting. Pooled immune serum (750 μg IgG per mouse) was passively transferred into naïve wild-type or Hvem knockout mice 24 h prior to lethal skin challenge. Results: Repeated exposure to HSV-1 or HSV-2 induced an increase in total HSV-binding IgG but did not boost neutralizing titers. In contrast, ADCC-mediating responses increased significantly from the first to the fourth viral exposure (p < 0.01). The increase was associated with an expanded antigenic repertoire. Passive transfer of fourth round immune serum provided significant protection whereas first round serum failed to protect (p < 0.01). However, protection was lost when serum was transferred into Hvem knockout mice, which are impaired in mediating ADCC killing. Conclusion: This novel model recapitulates clinical responses, highlights the importance of ADCC in protecting against recurrent infection, and provides a strategy for evaluating therapeutic vaccines.

Atypical presentation of herpes simplex virus 2 primary infection: a case report

BackgroundCervicitis, an infectious or noninfectious inflammation of the cervix, encompasses a wide range of clinical conditions, from asymptomatic infections to severe lesions, making its diagnosis difficult. Acute cervicitis may develop into pelvic inflammatory disease. In patients with cervicitis, current guidelines recommend testing for herpes simplex virus when external genital lesions are present. Here, we present the case of a patient with an atypical primary herpes simplex virus 2 infection manifesting as cervicitis without genital lesions.Case presentationA 29-year-old Caucasian woman was hospitalized for pelvic inflammatory disease. The patient complained of severe suprapubic pain, fever, and heavy vaginal discharge. The external genitalia were unremarkable, so empirical antibiotic treatment was initiated. Despite 48 hours of well-administered antibiotic therapy, her complaints persisted. Polymerase chain reaction for possible microbial causes was negative for Chlamydia trachomatis and Neisseria gonorrhoeae. There was no bacterial vaginosis. Repeat gynecological examinations with endovaginal ultrasound revealed an enlarged cervix, and pelvic magnetic resonance imaging supported a diagnosis of cervicitis. At this point, additional screening for other sexually transmitted infections and infectious disease-related etiologies of cervicitis was performed, and the polymerase chain reaction analysis of newly isolated samples was positive for herpes simplex virus 2. No antiviral treatment was initiated given the delay in diagnosing herpes simplex virus 2 infection and the slow but spontaneous abatement of symptoms.ConclusionHerpes simplex virus infection should be considered as a possible cause of cervicitis, even in the absence of typical genital lesions. Early detection of herpes simplex virus allows early treatment, helping to reduce the duration and severity of symptoms and therefore potentially reducing recurrences and improving disease control. These data and data from future cases might spur changes in the guidelines on cervicitis testing and treatment.

Centrifugal Microfluidic Cell Culture Platform for Physiologically Relevant Virus Infection Studies: A Case Study with HSV-1 Infection of Periodontal Cells.

Static well plates remain the gold standard to study viral infections in vitro, but they cannot accurately mimic dynamic viral infections as they occur in the human body. Therefore, we established a dynamic cell culture platform, based on centrifugal microfluidics, to study viral infections in perfusion. To do so, we used human primary periodontal dental ligament (PDL) cells and herpes simplex virus-1 (HSV-1) as a case study. By microscopy, we confirmed that the PDL cells efficiently attached and grew in the chip. Successful dynamic viral infection of perfused PDL cells was monitored using fluorescent imaging and RT-qPCR-based experiments. Remarkably, viral infection in flow resulted in a gradient of HSV-1-infected cells gradually decreasing from the cell culture chamber entrance towards its end. The perfusion of acyclovir in the chip prevented HSV-1 spreading, demonstrating the usefulness of such a platform for monitoring the effects of antiviral drugs. In addition, the innate antiviral response of PDL cells, measured by interferon gene expression, increased significantly over time in conventional static conditions compared to the perfusion model. These results provide evidence suggesting that dynamic viral infections differ from conventional static infections, which highlights the need for more physiologically relevant in vitro models to study viral infections.

Herpes Simplex Virus-1 Complicated by Postherpetic Neuralgia: A Case Report

BACKGROUND: The following case describes management of severe persistent vulvar pain from postherpetic neuralgia through a ganglion impar block. CASE REPORT: A 21-year-old female patient initially presented with genital lesions consistent with herpes simplex virus-1 (HSV-1) and antibody testing suggestive of primary HSV-1 infection. After her genital lesions resolved, she continued to have severe persistent vulvar pain and was diagnosed with postherpetic neuralgia, approximately one year after initial presentation. After unsuccessful medical management with her gynecologist and primary care physician, she was referred to a specialty pain management clinic, where a ganglion impar block was performed and provided significant pain relief. CONCLUSIONS: Genital HSV-1 is a rare cause of postherpetic neuralgia which can cause debilitating pain. Its management requires a multidisciplinary approach, including gynecology, pain management, physiatry, and if appropriate, behavioral health. KEY WORDS: Vulvar pain, postherpetic neuralgia, ganglion impar block, genital pain, case report

A comprehensive approach to oral health from the epidemiology of acute herpetic gingivostomatitis in pediatric patients

Introduction: Acute herpetic gingivostomatitis (AHGE) is the most common clinical manifestation of primary herpes simplex virus type 1, infection. It is a childhood disease, more frequent in infants and children under 6 years of age. Methods: an observational, descriptive, cross-sectional study was carried out in pediatric patients between the ages of 0 and 18 who attended with signs and symptoms of acute herpetic gingivostomatitis in the period from January 2022 to January 2023 at the dental clinic “AntonioBriones Montoto”, Pinar del Río, Cuba. The universe consisted of 156 children and the sample, obtained by simple random sampling, by 65 children according to the established inclusion and exclusion criteria. Descriptive and inferential statistics were used. The results were presented in tables and graphs to facilitate analysis and discussion. Results: there was a prevalence of acute herpetic gingivostomatitis in the ages of 2 and 6 years for 52,3 %. The most frequently detected signs and symptoms were pain in 100 %, difficulty in eating food in 87,7 %. The main risk factors were: catarrhal states with 40,0 % and febrile states 27,7 %. The level of knowledge about oral health was classified as regular with 44,6 %. Conclusions: ignorance of the causes, treatment and evolution of GEHA is the consequence of poor health education, hence the need to establish educational programs with a view to reducing the incidence and prevalence of oral diseases.

Herpes simplex virus dissemination with necrotizing hepatitis following Descemet membrane endothelial keratoplasty

BackgroundCorneal transplants are the most common type of transplant and increasing in frequency. Donor cornea tissues are a rare source of herpes simplex virus (HSV) transmission and not routinely tested for presence of HSV. Donor graft-to-recipient transmission typically causes graft failure and anterior uveitis, and extra-ocular HSV disease has not been previously reported. We present a case of HSV transmission from donor cornea tissue that nearly cost the corneal transplant recipient his life.Case reportAn elderly immunocompetent man developed an acute illness 10 days after having donor corneal tissue implanted in a Descemet membrane endothelial keratoplasty (DMEK). He was found to have HSV necrotizing hepatitis per liver biopsy, trilineage cytopenia, rhabdomyolysis, acute kidney failure, altered mental status, early-stage hemophagocytic lymphohistiocytosis (HLH), and donor corneal tissue implant infection resulting in graft failure and anterior uveitis. HSV DNA was detected in cerebral spinal fluid, peripheral blood, explanted donor corneal tissue, and anterior chamber fluid (220 million HSV DNA copies per mL). HSV-1 seroconversion denoted a primary HSV infection, and the patient had no other risk factor for HSV acquisition. Early recognition of HSV dissemination prompting treatment with intravenous acyclovir, as well as a short course of HLH-directed therapy, resolved the systemic illness. Vision was restored to near normal by replacement of the infected corneal graft with new donor DMEK tissue in conjunction with intravitreal foscarnet treatment.ConclusionAwareness of the potential risk of donor cornea tissue transmitting HSV and leading to life-threatening HSV disease is paramount to early diagnosis and treatment. The role of donor cornea tissue in HSV transmission and disease merits additional attention and investigation.

Febbre e gengivostomatite: non è sempre solo herpes simplex

Gingivostomatitis is a clinical condition frequently diagnosed by the family paediatrician and it generally shows a viral aetiology. In particular, primary herpes simplex infection is the most frequent cause of gingivostomatitis in toddlers and it typically presents with fever and gingival/oral inflammation and ulcerations. Besides, gingivostomatitis and fever can be present at the onset of acute myeloid leukaemia (AML), a rare type of childhood cancer with an incidence of 7 cases per 1 million children &lt; 15 years. This paper describes the case of a 3-year-old boy who presented with fever and gingivostomatitis initially misdiagnosed as a primary herpetic infection, while it turned out to be a clinical onset of an AML with hyperleukocytosis, a condition at high-risk of mortality.

Clinical progress note: Evaluation and management of neonatal herpes simplex virus disease.

Clinical progress note: Evaluation and management of neonatal herpes simplex virus disease.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Herpes Simplex Virus Seroprevalence among Pregnant Finnish Women and Their Spouses-A Six-Year Follow-Up Cohort Study.

The aim was to evaluate the herpes simplex virus (HSV) seroprevalence and seroconversion among 285 pregnant women and their 120 male spouses in Finland during a six-year follow-up (FU) between 1998–2008. We also studied the effect of sexual habits, pregnancy, and other demographic factors on the acquisition of HSV infection. Combined HSV-1 and HSV-2-IgG antibodies were assessed in the first baseline serum samples with an indirect enzyme immunoassay method. The individuals with seronegative or borderline HSV serology at baseline were additionally tested using their latest FU serum sample available. The overall HSV seroprevalence during the FU was 58.9% (168/285) among the women and 53.3% (64/120) among their spouses. The seroconversion rate was 11.4% (15/132) and 12.5% (8/64) among women and their spouses, respectively. Both spouses were HSV seropositive in 39.2% (47/120). To determine the HSV-2 seroprevalence, we also tested all HSV-seropositive participants using HSV-2-specific antigen. HSV-2 seropositivity was detected in 10.9% (44/405) of the participants. The age (p = 0.006) and history of genital warts (p = 0.006) of the women were associated with combined HSV-1 and/or HSV-2 seropositivity, while a younger age was related to HSV seroconversion (p = 0.023). Among the male spouses, HSV seropositivity was associated with the practice of oral sex (p = 0.033). To conclude, women of childbearing age acquire primary HSV infections and the presence of HSV in oral epithelium is common among HSV-seropositive individuals.

Infecciones por el virus del grupo herpes

The Herpesviridae family includes nine subtypes that are pathogenic in human beings. They belong to three subfamilies: α-herpesvirus (herpes simplex 1 and 2, varicella zoster, and herpes B virus); β-herpesvirus (cytomegalovirus, human herpesvirus 6, and human herpesvirus 7), and γ-herpesvirus (Epstein-Barr virus and human herpesvirus 8). All herpesviruses have in common the ability to establish latency and reactive in situations of immunosuppression. Primary herpes simplex 1 and 2 infection remains latent in regional nerve ganglions and has periodic reactivations. It has a lower morbidity than the original infection. The primary varicella zoster virus infection is responsible for varicella whereas the reactivations manifest as shingles. Herpesvirus type 6A gives rise to encephalitis in adults and herpesvirus type 6B gives rise to sudden exanthem in children. Herpesvirus type 8 is associated with Kaposi's sarcoma, multicentric Castleman disease, and body cavity lymphoma.

Primary herpes simplex virus type 1 infection with acute liver failure in solid organ transplantation: Report of three cases and review

Herpes virus infections is not uncommon in solid organ transplantation patients. We report 3 cases with primary Herpes simplex virus type-1 (HSV1) infection with acute liver failure (ALF). This is a rare and potentially fatal entity that could be a donor-derived infection. Although the initial clinical presentation is non-specific, it should be considered as a differential diagnosis in HSV-negative serology patients with liver failure and empirical treatment must be started in combination with a drastic reduction of immunosuppression. A strategy of HSV prophylaxis for pre-transplant HSV seronegative patients must be stablished in order to reduce the risk of clinical disease.

Primary herpetic oropharyngitis in adults: Differences in clinical features between Herpes simplex virus type 1 and type 2. A retrospective study.

This is the first report on the differences between adult primary herpetic oropharyngitis caused by the two types of the herpes simplex virus (HSV). Forty-one (25 type 1 and 16 type 2) HSV specific antigen positive cases among 68 immunoserologically confirmed adult primary HSV infection cases were investigated. A significantly low incidence of oral lesions and high incidence of nausea were seen in HSV type 2 oropharyngitis cases, which potentially indicates an association between the vagus nerve and HSV type 2 infection. Significantly increased white blood cell count and elevated C-reactive protein level were observed in HSV type 2 oropharyngitis cases. HSV type 2 possibly causes more severe symptoms and inflammatory reactions than HSV type 1.

When obstetrics\u2013gynecology specialists need to call an ophthalmologist urgently: a case report

BackgroundWe report here a case of a healthy 23-year-old female patient who was assessed at the gynecology emergency department for genital ulcers, fever, and blurred vision. After suspicion of herpes simplex virus-2 lesions, the diagnosis of Behçet’s disease was made. We report this case with the aim of including Behçet’s disease in the differential diagnosis of genital ulcers, and emphasize the emergency of the vision loss that can be irreversible.Case presentationA healthy 23-year-old European female patient was assessed by gynecology in the emergency department for genital lesions associated with fever and blurred vision. At first, these lesions were suspected to be primary herpes simplex virus-2 infection One day later, she experienced decreased visual acuity in both eyes. After 4 days of worsening genital ulcers and persistent blurred vision, the patient was referred to the ophthalmology department. Fundoscopic examination showed retinal hemorrhages that were consistent with the first presentation of Behçet’s disease.ConclusionsThis case demonstrates that genital ulcers can be the very initial symptom of this ophthalmologic emergency. The differential diagnosis of genital ulcers is challenging. Behçet’s disease should be included, especially when associated with systemic or ocular manifestations, and should be considered an emergency for the gynecologist to prevent long-term vision loss.

Primary Herpes Simplex viral infection of bilateral nipples and areolae with reactive arthritis: An uncommon presentation of a common disease

Herpes Simplex Viruses (HSV) are members of the Herpesvirales, subfamily Alphaherpesvirinae. They are linear double standard DNA viruses. Skin manifestations caused by HSV is one of the commonest cutaneous infectious diseases encountered during dermatology practice. It affects most people on one or more occasions during their lives. Cutaneous presentations are characterized by painful localized grouped vesicles. Type 1 HSV is mainly associated with orofacial involvement. Type 2 HSV is mainly associated with anorectal involvement. However, HSV infection can occur almost any area of skin or mucous membrane.

Cell-to-cell transmission of HSV1 in human keratinocytes in the absence of the major entry receptor, nectin1.

Herpes simplex virus 1 (HSV1) infects the stratified epithelia of the epidermis, oral or genital mucosa, where the main cell type is the keratinocyte. Here we have used nTERT human keratinocytes to generate a CRISPR-Cas9 knockout (KO) of the primary candidate HSV1 receptor, nectin1, resulting in a cell line that is refractory to HSV1 entry. Nonetheless, a small population of KO cells was able to support infection which was not blocked by a nectin1 antibody and hence was not a consequence of residual nectin1 expression. Strikingly at later times, the population of cells originally resistant to HSV1 infection had also become infected. Appearance of this later population was blocked by inhibition of virus genome replication, or infection with a ΔUL34 virus defective in capsid export to the cytoplasm. Moreover, newly formed GFP-tagged capsids were detected in cells surrounding the initial infected cell, suggesting that virus was spreading following replication in the original susceptible cells. Additional siRNA depletion of the second major HSV1 receptor HVEM, or PTP1B, a cellular factor shown elsewhere to be involved in cell-to-cell transmission, had no effect on virus spread in the absence of nectin1. Neutralizing human serum also failed to block virus transmission in nectin1 KO cells, which was dependent on the receptor binding protein glycoprotein D and the cell-to-cell spread glycoproteins gI and gE, indicating that virus was spreading by direct cell-to-cell transmission. In line with these results, both HSV1 and HSV2 formed plaques on nectin1 KO cells, albeit at a reduced titre, confirming that once the original cell population was infected, the virus could spread into all other cells in the monolayer. We conclude that although nectin1 is required for extracellular entry in to the majority of human keratinocytes, it is dispensable for direct cell-to-cell transmission.

COVID-19 and Herpes Simplex Virus Infection: A Cross-Sectional Study.

BackgroundDespite being variable and poorly characterized, the reported cutaneous manifestations of coronavirus disease 2019 (COVID-19) are of increasing concern.MethodologyThis study aimed to determine the prevalence and possible association between COVID-19 and herpes simplex virus (HSV) infection. A nine-item questionnaire was sent to 120 polymerase chain reaction-confirmed COVID-19 patients with a response rate of 66.67%. This cross-sectional observational study included 80 patients with mild-to-moderate COVID-19 infection who did not require hospitalization or steroid therapy.ResultsOne or more HSV infections were observed in 28 patients (35%) with COVID-19 infection, including 10 (35.7%) males and 18 (64.29%) females. Of the 28 patients, fever was reported in 17 (75%) during COVID-19. Most of the respondents (78%) described a single HSV reactivation, 14.29% had two attacks, and 7.14% experienced three attacks. Compared to previous non-COVID-19-related HSV reactivation, the COVID-19-related attacks were more severe in 12 (42.85%) patients, equally severe in five (17.85%) patients, and less severe in one (3.57%) patient. Interestingly, 10 (35.71%) patients developed an initial symptomatic HSV attack during COVID-19 infection.ConclusionsThis study demonstrated a possible association between COVID-19 infection and primary HSV infection or reactivation. COVID-19 direct neuronal effect in addition to COVID-19-related psychological stress, fever, and immunological dysregulation could play a potential role in HSV reactivation or primary infection during COVID-19.

MANAGEMENT OF HSV-1 AND HSV-2 PRIMARY INFECTION IN ADULT PATIENT: A CASE REPORT

ABSTRACT Infection of Herpes Simplex Virus (HSV) type 1 and 2 causes medical problems throughout the world. HSV-1 infection often affects the oral regions and HSV-2 infection is the most prevalent cause of genital ulcerations. It is possible for HSV-2 to cause oro-labial herpes and HSV-1 to cause genital herpes. Primary HSV infection usually affects children or adolescent, whereas adults usually experience infection more frequently due to viral reactivation. Objective: To discuss the management of Primary HSV-1 and HSV-2 Infection which appears simultaneously in adults. Case report: a 33yearold female patient came to hospital with multiple painful ulcers in her tongue, buccal and labial mucosa, preceded by prodrome, followed with eruption and outbreak of vesicles on her skin. The first laboratory examination confirmed a high titer of reactive Immunoglobulin M (IgM) of anti-HSV-1 and Immunoglobulin M (IgM) anti-HSV-2. She was diagnosed to have Primary HSV-1 and HSV-2 Infection and treated with oral Acyclovir and Chlorine dioxide mouthwash with good healing. The clinical presentation, differential diagnosis and management of primary herpetic stomatitis are discussed. Conclusion: Correct diagnosis and treatment can restore well-being, avoid secondary problems for patients, and prevent the use of inappropriate drugs.Keywords : Herpes Simplex Virus, HSV-1, HSV-2, Management, Primary Herpes Infection

Primary herpes simplex virus type 2 hepatitis diagnosed during laparoscopy

Primary herpes simplex virus type 2 hepatitis diagnosed during laparoscopy

Primary Herpes Simplex Virus Type 2 Infection Associated With Monoarthritis of the Knee

Abstract Monoarthritis associated with herpes virus infection is rare and previously only described in herpes simplex type 1, varicella zoster, and Epstein-Barr virus infections. Here, we report a case of monoarthritis of the knee associated with primary herpes simplex virus type 2 (HSV-2) infection in an immunocompetent 50-year-old woman. Herpes simplex virus type 2 DNA was detected in plasma and in the joint fluid. The patient had only mild symptoms of herpes simplex virus type 2, suggesting that virus-associated monoarthritis may be underrecognized and underreported.