Search Results (14)

We aim to investigate the role of the Herpesviridae family (HHV) in the onset and progression of prostate cancer (PCa) and to profile the local PCa immunological status. A total of 116 “tru-cut” biopsies (58 PCa and 58 benign prostatic hyperplasia [BPH]) and 49 formalin-fixed paraffin-embedded (FFPE) instances of PCa were analysed using real-time qPCR and histological examination. Infection with CMV, EBV, HHV6, and HHV7 was detected in 11.5% of the “tru-cut” biopsies (25.9% in BPH and 6.9% in the PCa group). In the formalin-fixed paraffin-embedded (FFPE) samples, infection was detected in 69.4% of the patients, with individual rates of EBV (47%), HHV6 (38%), HHV7 (41%), CMV (2.9%), HSV2 (2.9%), and VZV (5.8%). In the HHV-infected PCa cases, the histopathological landscape included intratumor lymphocyte infiltration with fibrosis and necrosis, periductal chronic inflammatory reaction and granulomatous lesions with foci of abscesses and necrosis, as well as inflammatory infiltration, chronic lymphadenitis, prostatic intraepithelial atrophy (PIA), and high-grade prostatic intraepithelial neoplasia (HGPIN). The majority of HHV-infected PCa patients were predominantly classified as grade G3/G4/G5 tumours, exhibiting perineural, perivascular, and lymphovascular invasion, seminal vesicle invasion, senile vesicle amyloidosis, and lymph node metastasis. Statistical analysis demonstrated a significant association between HHV infection and PCa (χ² ≈ 20.3, df = 1, p < 0.0001; Fisher’s exact test, p < 0.0001) with an odds ratio of 6.50 (95% CI: 2.80–15.12). These findings suggest that long-term HHV infection could contribute to a complicated and potentially altered immune PCa tumour environment due to inflammation. This may serve as a predictor of aggressive disease progression. Full article

Human herpesvirus 6 (HHV-6) is a ubiquitous virus with significant implications for immunocompromised individuals, particularly people living with HIV (PLWH). This study aimed to estimate the prevalence of HHV-6 detection in blood samples among PLWH using molecular diagnostic techniques. A systematic literature search was conducted across multiple databases until September 2024, including studies that reported HHV-6 detection in blood samples of PLWH through molecular methods. The meta-analysis calculated pooled prevalence rates using a random-effects model and assessed study quality, with additional analyses for outlier identification and influential study effects. Twelve studies met the inclusion criteria, and the random-effects model estimated the prevalence of HHV-6 detection at 11.7% (95% CI: 4.3–21.8%), with considerable heterogeneity. Influence diagnostics identified one study as influential, and after its exclusion, the recalculated pooled prevalence was 8% (95% CI: 4.4–12.4%), with reduced but still considerable heterogeneity. This meta-analysis highlights the prevalence of HHV-6 detection in PLWH, emphasizing the need for ongoing research to explore the clinical implications and factors influencing viral detection as well as the implications of this coinfection on the treatment and overall health of PLWH. Full article

Background/Objectives: Pityriasis rosea (PR) is a self-limiting exanthematous disease associated with the endogenous reactivation of human herpesviruses (HHV)-6 and HHV-7. Classically, the lesions gradually resolve, leaving no sequelae. Therefore, the best treatment is reassuring the patient and suggesting a resting period. However, atypical PR cases characterized by extensive, persistent lesions and systemic symptoms may impact the patient’s quality of life, and, therefore, a treatment can be prescribed. There is limited evidence on the comparative effectiveness of pharmacological treatments for PR; therefore, we performed a network meta-analysis to compare these interventions. Methods: Overall, 12 randomized control trials (RCTs) were identified. The outcomes were itch resolution and rash improvement. Results were expressed as risk ratio (RR) and 95% confidence interval (CI). We also calculated the relative ranking of the interventions for achieving the aforementioned outcomes as their surface under the cumulative ranking (SUCRA). Results: On network meta-analysis, only oral steroids and the combination of oral steroids+antihistamine resulted significantly superior to the placebo in terms of itch resolution (RR 0.44, CI 0.27–0.72 and RR 0.47, CI 0.22–0.99). Oral steroids resulted in the best treatment (SUCRA 0.90) for itch resolution. In terms of rash improvement, only acyclovir and erythromycin resulted significantly superior to placebo (RR 2.55, CI 1.81–3.58; and RR 1.69, CI 1.23–2.33), and acyclovir outperformed all the other tested interventions. Consequently, acyclovir ranked as the best intervention (SUCRA score 0.92). Conclusions: Acyclovir represents the best option for patients with PR that have extensive, persistent lesions or systemic symptoms. Steroids and antihistamines seemed the best treatment for itch resolution. Full article

Leukocytosis in neonates can occur because of infectious, inflammatory, malignant, or physiological processes. Hyperleukocytosis is defined as a total leukocyte count (TLC) exceeding 100,000 per mm³, warranting immediate evaluation. Neonates with hyperleukocytosis are at risk of leukostasis and the associated severe complications, including respiratory distress, myocardial ischemia, hyperuricemia, acute renal failure, infarction, and hemorrhage. Differentiating leukemia and leukemoid reactions in neonates presenting with elevated TLC is challenging but critical. We present a unique case of a preterm male neonate with hyperleukocytosis, initially suspected to have an underlying malignancy. The neonate’s clinical course was complicated by respiratory distress syndrome and anemia of prematurity, necessitating neonatal intensive care unit management. Further investigation revealed high human herpesvirus 6 (HHV-6) DNA levels in the whole blood, leading to a chromosomally integrated HHV-6 (ciHHV-6) diagnosis. CiHHV-6 is characterized by HHV-6 DNA integration into the host genome. Accurate diagnosis relies on whole-blood quantitative PCR, distinguishing ciHHV-6 from an active infection. The neonate remained asymptomatic, and antiviral treatment was deemed unnecessary. This case underscores the importance of recognizing ciHHV-6 as a potential cause of hyperleukocytosis in neonates and highlights the value of whole-blood PCR for differentiation. Understanding the spectrum of HHV-6 infection in neonates is vital for appropriate management and prognostication. Full article

HHV-6B reactivation affects approximately half of all allogeneic hematopoietic cell transplant (HCT) recipients. HHV-6B is the most frequent infectious cause of encephalitis following HCT and is associated with pleiotropic manifestations in this setting, including graft-versus-host disease, myelosuppression, pneumonitis, and CMV reactivation, although the causal link is not always clear. When the virus inserts its genome in chromosomes of germ cells, the chromosomally integrated form (ciHHV6) is inherited by offspring. The condition of ciHHV6 is characterized by the persistent detection of HHV-6 DNA, often confounding diagnosis of reactivation and disease—this has also been associated with adverse outcomes. Recent changes in clinical practice in the field of cellular therapies, including a wider use of post-HCT cyclophosphamide, the advent of letermovir for CMV prophylaxis, and the rapid expansion of novel cellular therapies require contemporary epidemiological studies to determine the pathogenic role and spectrum of disease of HHV-6B in the current era. Research into the epidemiology and clinical significance of HHV-6B in chimeric antigen receptor T cell (CAR-T cell) therapy recipients is in its infancy. No controlled trials have determined the optimal treatment for HHV-6B. Treatment is reserved for end-organ disease, and the choice of antiviral agent is influenced by expected toxicities. Virus-specific T cells may provide a novel, less toxic therapeutic modality but is more logistically challenging. Preventive strategies are hindered by the high toxicity of current antivirals. Ongoing study is needed to keep up with the evolving epidemiology and impact of HHV-6 in diverse and expanding immunocompromised patient populations. Full article

Human herpes virus 6A (HHV-6A) is able to integrate into the telomeric and subtelomeric regions of human chromosomes representing chromosomally integrated HHV-6A (ciHHV-6A). The integration starts from the right direct repeat (DR_R) region. It has been shown experimentally that perfect telomeric repeats (pTMR) in the DR_R region are required for the integration, while the absence of the imperfect telomeric repeats (impTMR) only slightly reduces the frequency of HHV-6 integration cases. The aim of this study was to determine whether telomeric repeats within DR_R may define the chromosome into which the HHV-6A integrates. We analysed 66 HHV-6A genomes obtained from public databases. Insertion and deletion patterns of DR_R regions were examined. We also compared TMR within the herpes virus DR_R and human chromosome sequences retrieved from the Telomere-to-Telomere consortium. Our results show that telomeric repeats in DR_R in circulating and ciHHV-6A have an affinity for all human chromosomes studied and thus do not define a chromosome for integration. Full article

Human herpesvirus 8 (HHV-8), the causative agent of Kaposi’s sarcoma, multicentric Castleman’s disease and primary effusion lymphoma, predominantly manifests in immunocompromised individuals. However, infection in immunocompetent individuals does occur. The prevalence of HHV-8 exposure in blood donors from non-endemic countries ranges between 1.2% and 7.3%. Nothing was known about the prevalence in Australian blood donors. Therefore, this study investigated the active and cumulative exposure of HHV-8 in this cohort. Plasma samples (n = 480) were collected from eastern Australian blood donors and were tested for HHV-8 DNA by qPCR, and for HHV-8 antibodies by two different ELISAs. Samples initially positive on either ELISA were retested in duplicate on both, and on a mock-coated ELISA. Any samples positive two or three out of the three times tested on at least one ELISA, and repeat negative on the mock-coated ELISA, were assigned as repeat positive. None of the 480 samples tested contained HHV-8 DNA. Serological testing revealed 28 samples (5.83%; 95% CI: 3.74–7.93%) had antibodies to HHV-8. There was no difference (p > 0.05) in seropositivity between sex or with increasing age. This is the first study to show serological evidence of cumulative HHV-8 exposure and no HHV-8 DNAemia within a select blood donor population in Australia. Our molecular and serological data is consistent with published results for blood donors residing in HHV-8 non-endemic countries, which shows the prevalence to be very low. Full article

Enterovirus infection is a known risk factor for type 1 diabetes (T1DM). Whether infection with other viruses induces T1DM remains undetermined. This study investigated the association between human herpesvirus (HHV) infection and the development of T1DM, using the data from Taiwan’s National Health Insurance Research Database. Patients with T1DM and age- and sex-matched controls were included. Subjects with HHV infection were subgrouped into those with histories of varicella-zoster virus, herpes simplex virus (HSV), Epstein-Barr virus, and human cytomegalovirus infections. The odds ratio of the risk of T1DM was calculated using a multivariable conditional logistic regression model. Atopic diseases, autoimmune thyroid diseases, and history of enterovirus infection served as adjusted comorbidities. Our findings suggested a significant association between HSV infection and the risk of T1DM (adjusted odds ratio: 1.21; 95% CI: 1.01–1.47, p = 0.048), while infection with other HHVs was not. The result of HSV infection remained significant when subjects were restricted to age ≤ 18 years (adjusted odds ratio: 1.35; 95% CI: 1.08–1.70, p = 0.010). We found a history of HSV infection might be an independent predictive risk factor for T1DM. This could be potentially helpful to the practice in public health. Full article

Inherited chromosomally integrated (ici) human herpes virus 6 (HHV-6) is estimated to occur in 0.6–2.7% of people worldwide. HHV-6 comprises two distinct species: HHV-6A and HHV-6B. Both HHV-6A and HHV-6B integration have been reported. Several drugs are capable of activating iciHHV-6 in tissues, the consequences of which are poorly understood. We report herein a case of a woman with iciHHV-6A+ and iciHHV-6B+, who developed ulipristal acetate (a selective progesterone receptor modulator)-induced fulminant hepatic failure that required liver transplantation. We confirmed the presence of ~one copy per cell of both HHV-6A and HHV-6B DNA in her hair follicles using multiplex HHV-6A/B real-time PCR and demonstrated the Mendelian inheritance of both iciHHV-6A and iciHHV-6B in her family members over three generations. Because of the rarity of this presentation, we discuss herein the possible links between reactivated HHV-6 from iciHHV-6A and/or iciHHV-6B and adverse drug reactions, suggesting that iciHHV-6 could be screened before the introduction of any hepatotoxic drugs to exclude HHV-6 active disease or combined idiosyncratic drug-induced liver injury in these patients. Full article

Our aim was to investigate the usefulness of 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in the diagnosis, treatment response evaluation, and follow-up of human herpesvirus-8 (HHV-8)-associated multicentric Castleman’s disease (MCD). Fifteen patients with histologically diagnosis of HHV-8-associated MCD were retrospectively included. For all patients, a ¹⁸F-FDG PET/CT scan was performed before any treatment for diagnosis and PET/CT scans after Rituximab (4 cycles) for the evaluation of treatment response; moreover, 22 PET/CT were performed during the follow-up to check disease status. To evaluate treatment response, we applied Deauville criteria. PET/CT findings were compared with other conventional imaging (CI) findings. At diagnosis, ¹⁸F-FDG PET/CT showed an increased FDG-uptake in all cases corresponding to lymph nodes and confirming the MCD. The average SUVmax of the FDG avid lesions were 8.75, average lesion-to-liver SUVmax ratio was 3.6, and average lesion-to-blood pool SUVmax ratio was 3.9. After first-line therapy, ¹⁸F-FDG PET/CT resulted negative (Deauville score < 4) in seven patients and positive in the remaining eight (Deauville score 4–5). A negative restaging PET/CT was associated with a lower risk of relapse. During follow-up, PET/CT detected the presence of relapse or progression in 5 (23%) cases with an accuracy higher than CI. ¹⁸F-FDG PET/CT seems to be an useful tool in studying HHV-8-associated MCD both at diagnosis and during follow-up. Full article

Human herpes virus type 8 (HHV-8) is the causative agent of Kaposi’s sarcoma (KS). We systematically reviewed literature published between 1998 and 2017, according to the PRISMA guidelines, to understand the distribution of HHV-8 infection in Africa. More than two-thirds (64%) of studies reported on seroprevalence and 29.3% on genotypes; 9.5% were on both seroprevalence and genotypes. About 45% of African countries had data on HHV-8 seroprevalence exclusively, and more than half (53%) had data on either seroprevalence or genotypes. Almost half (47%) of the countries had no data on HHV-8 infection. There was high heterogeneity in the types of tests and interpretation algorithms used in determining HHV-8 seropositivity across the different studies. Generally, seroprevalence ranged from 2.0% in a group of young children in Eritrea to 100% in a small group of individuals with KS in Central African Republic, and in a larger group of individuals with KS in Morocco. Approximately 16% of studies reported on children. Difference in seroprevalence across the African regions was not significant (95% CI, χ² = 0.86; p = 0.35), although specifically a relatively significant level of infection was observed in HIV-infected children. About 38% of the countries had data on K1 genotypes. K1 genotypes A, A5, B, C, F and Z occurred at frequencies of 5.3%, 26.3%, 42.1%, 18.4%, 5.3% and 2.6%, respectively. Twenty-three percent of the countries had data for K15 genotypes, and genotypes P, M and N occurred at frequencies of 52.2%, 39.1%, and 8.7%, respectively. Data on HHV-8 inter-genotype recombinants in Africa are scanty. HHV-8 may be endemic in the entire Africa continent but there is need for a harmonized testing protocol for a better understanding of HHV-8 seropositivity. K1 genotypes A5 and B, and K15 genotypes P and M, from Africa, should be considered in vaccine design efforts. Full article

Human herpesvirus 6A and 6B, alongside some other herpesviruses, have the striking capacity to integrate into telomeres, the terminal repeated regions of chromosomes. The chromosomally integrated forms, ciHHV-6A and ciHHV-6B, are proposed to be a state of latency and it has been shown that they can both be inherited if integration occurs in the germ line. The first step in full viral reactivation must be the release of the integrated viral genome from the telomere and here we propose various models of this release involving transcription of the viral genome, replication fork collapse, and t-circle mediated release. In this review, we also discuss the relationship between ciHHV-6 and the telomere carrying the insertion, particularly how the presence and subsequent partial or complete release of the ciHHV-6 genome may affect telomere dynamics and the risk of disease. Full article

Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated “CiHHV-6A/B”. These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections. Full article

To elucidate and compare the seroprevalence of human herpesvirus 8 (HHV8) and hepatitis C virus (HCV) among Chinese drug users, a cross-sectional study of 441 participants, was conducted in Shanghai, China, from 2012 through 2013. Seventy-seven (17.5%) participants were found to be positive for HHV8 antibodies, while 271 (61.5%) participants were positive for HCV. No significant association between HHV8 seropositivity and drug use characteristics, sexual behaviors, HCV, or syphilis was observed. In contrast, a statistically significant association between HCV seropositivity and injected drug history (OR, 2.18, 95% CI 1.41–3.37) was detected, whereas no statistically significant association between HCV seropositivity and syphilis infection (OR, 7.56, 95% CI 0.94–60.57) were observed. Pairwise comparisons showed no significant differences between latent and lytic antibodies regarding HCV and HHV8 serostatus. The study demonstrated a moderate but elevated prevalence of HHV8 infection among drug users. The discordance between HHV8 and HCV infections suggests that blood borne transmission of HHV8 might not be the predominant mode of transmission in this population, which is in contrast to HCV. Full article