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The herpes simplex viruses consist of the strains, HSV-1 and HSV-2, which are prevalent worldwide and lack a definitive cure. We aimed to explore the specific characteristics of HSV 1 and 2 infections, such as differences between gender assigned at birth, age at infection, site of infection, comorbidities, and effect of pregnancy, through a data analysis. Between 2011 and 2018, the Israeli Central Virology Laboratory diagnosed 9189 samples using multiplexed real-time PCR. In addition, we extracted all of the medical data for 287 females hospitalized at the Sheba Medical Center with HSV-1 (161) or HSV-2 (126) genital infections. HSV-2 was almost absent in the orofacial samples from both genders, while in other lesion sites, HSV-2 was significantly more abundant in females than in males (p < 0.05,). HSV-2 was initially detected at puberty. In the hospitalized females' malignancies, both HSV-1 and HSV-2 were found with a non-significant difference. Simultaneously, pregnancies were more common in females who were HSV-2-positive compared with those who were HSV-1-positive (27.8% vs. 12.4%, respectively, p < 0.01). Primary infections occur more with HSV-1 than with HSV-2 (15.6% vs. 3.2%, respectively). Our findings demonstrate that genital HSV-2 infection episodes are more frequent during pregnancy, suggesting that pregnancy may serve as a risk factor for HSV-2 reactivation or infection. [ABSTRACT FROM AUTHOR]

Herpes Simplex Virus (HSV) type 1 (HSV‐1) and type 2 (HSV‐2) are among the most common human viral pathogens, affecting several billion people worldwide. Although in healthy patients clinical signs and symptoms of HSV infection are usually mild and self‐limiting, HSV‐infections in immunocompromised patients are frequently more aggressive, persistent, and even life‐threatening. Acyclovir and its derivatives are the gold standard antiviral drugs for the prevention and treatment of HSV infections. Although the development of acyclovir resistance is a rather uncommon condition, it may be associated with serious complications, especially in immunocompromised patients. In this review, we aim to address the problem of drug resistant HSV infection and discuss the available alternative therapeutic interventions. All relative studies concerning alternative treatment modalities of acyclovir resistant HSV infection published in PubMed between 1989 to 2022 were reviewed. Long‐term treatment and prophylaxis with antiviral agents predisposes to drug resistance, especially in immunocompromised patients. Cidofovir and foscarnet could serve as alternative treatments in these cases. Although rare, acyclovir resistance may be associated with severe complications. Hopefully, in the future, novel antiviral drugs and vaccines will be available in order to avoid the existing drug resistance. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris is a rare autoimmune skin disease. Although herpes simplex virus has been associated with autoimmune diseases, evidence regarding its association with pemphigus vulgaris exacerbations is scarce. This retrospective cohort study aimed to characterize the epidemiological and clinical features of patients with pemphigus vulgaris who were herpes simplex-positive, compared with those who were herpes simplex-negative, during disease onset. Of 62 patients with pemphigus vulgaris who underwent PCR testing for herpes simplex virus, 25 (40.3%) were positive, with a mean age of 56.1 ± 15.5 years; 35.5% were male. The herpes-positive group had significantly elevated levels of C-reactive protein, Pemphigus Disease Activity Index score, and shorter time to relapse. The time to remission, number of exacerbations per year, and remission status were non-significantly elevated in the herpes-positive group. Thus, routine testing lesions from patients with pemphigus for herpes simplex virus should be performed. If positive, antiviral treatment should be initiated; and preventive antiviral treatment should be considered in severe cases. [ABSTRACT FROM AUTHOR]

Background: In recent years, liver transplantation (LT) has become a well‐accepted therapeutic modality for children with end‐stage liver disease, with transplantation surgery being performed at a younger age. Human herpes virus 6 (HHV‐6) infection occurs in most children within the first 2 years of life, therefore, data on primary HHV‐6 infection in pediatric liver transplant recipients is scarce. Objective: To describe the course of primary HHV‐6 infection after pediatric LT. Methods: Medical files, between the years 2015‐2016, of post‐LT pediatric patients with suspected primary HHV‐6 infection were reviewed. Clinical and laboratory data for enrolled cases were evaluated. Primary infection was defined as DNAemia in children who were seronegative prior to transplantation or seroconversion from negative to positive IgG posttransplantation. Results: Four cases of primary HHV‐6 (type B) infection were identified among the 26 children who had undergone LT at our center during the study period. All patients were <1 year old and presented with fever, hepatitis, and elevated inflammatory markers, most (75%) within a short‐period posttransplantation. All were initially treated with empiric antibiotics for a suspected bacterial infection and three underwent liver biopsy, one showing signs of rejection. Three were treated with antiviral therapy with a gradual resolution of symptoms. Discussion: Primary HHV‐6 should be taken into account in young children shortly after LT, especially when presenting with fever and elevated liver enzymes. Treatment with antiviral therapy should be considered. Conclusions: In young infants post‐LT, a high index of suspicion may promote early detection of HHV‐6 primary infection and prevent serious complications. [ABSTRACT FROM AUTHOR]

Abstract: Malignant melanoma is a highly aggressive tumor which frequently resists chemotherapy, therefore, the search for new agents for its treatment is of great importance. In this study, we purified the sesquiterpene lactones (SLs), Tomentosin and Inuviscolide from Inula viscosa (Compositae) leaves and studied their anti-cancer potency against human melanoma cell lines in order to develop new agents for melanoma treatment. SLs inhibited the proliferation of three human melanoma cell lines: SK-28, 624mel and 1363mel in a dose-dependent manner. We further investigated SLs mechanism of action using SK-28 as a representative cell line model. SLs caused cell-cycle arrest at G2/M, accompanied by the appearance of a sub-G0 fraction, indicative of apoptotic cell death. Induction of apoptosis was further confirmed by changes in membrane phospholipids, changes in mitochondrial membrane potential (ΔΨ) and by detection of Caspase-3 activity. Rapid inhibitory phosphorylation of Cdc2 (Thr14 and Tyr15) was seen early after treatment, followed by a later decrease in the expression level of both Cyclin b1 and Cdc2. Induction of p53 and p21waf1 proteins and phosphorylation of p53 at Ser15 were also detected early after treatment. The anti-apoptotic proteins, p65 subunit of nuclear factor κB (NF-κB), and Survivin were reduced in a dose-dependent manner. Taken together, these changes partially explain the ability of the SLs to induce G2/M arrest and apoptosis. Induction of apoptosis by Tomentosin and Inuviscolide in human aggressive melanoma cell lines has high pharmacological value and implies that SLs might be developed as new agents for melanoma treatment. [Copyright &y& Elsevier]

TPA (12-O-tetradecanoylphorbol-13-acetate), a well-known activator of protein kinase C (PKC), can experimentally induce reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) in certain latently infected cells. We selectively blocked the activity of PKC isoforms by using GF 109203X or rottlerin and demonstrated that this inhibition largely decreased lytic KSHV reactivation by TPA. Translocation of the PKCdelta isoform was evident shortly after TPA stimulation. Overexpression of the dominant-negative PKCdelta mutant supported an essential role for the PKCdelta isoform in virus reactivation, yet overexpression of PKCdelta alone was not sufficient to induce lytic reactivation of KSHV, suggesting that additional signaling molecules participate in this pathway., (Copyright 2004 American Society for Microbiology)