The Contribution of Human Herpes Viruses to γδ T Cell Mobilisation in Co-Infections

γδ T cells are activated in viral, bacterial and parasitic infections. Among viruses that promote γδ T cell mobilisation in humans, herpes viruses (HHVs) occupy a particular place since they infect the majority of the human population and persist indefinitely in the organism in a latent state. Thus, other infections should, in most instances, be considered co-infections, and the reactivation of HHV is a serious confounding factor in attributing γδ T cell alterations to a particular pathogen in human diseases. We review here the literature data on γδ T cell mobilisation in HHV infections and co-infections, and discuss the possible contribution of HHVs to γδ alterations observed in various infectious settings. As multiple infections seemingly mobilise overlapping γδ subsets, we also address the concept of possible cross-protection.

EARLY DIAGNOSTICS OF AUTOINFLAMMATORY DISORDERS ASSOCIATED WITH POST-VIRAL CHRONIC FATIGUE SYNDROME AND COGNITIVE IMPAIRMENTS IN CHRONIC MIXED HERPES VIRAL INFECTIONS

The steady increase in the number of autoimmune diseases and immune-mediated autoinflammatory processes causes an increased interest of doctors of all specialties in this topic and makes the issue of early detection of autoimmune disorders / autoimmune syndrome (AS) extremely urgent. These disorders often develop against the backdrop of an atypical stream of chronic active viral infections caused by persistent viruses, in particular those of the Herpesviridae family, and remain undiagnosed due to polysymptomatic disease, and various “clinical masks” of the disorders caused by them. The semi-quantitative method developed by us for screening assessment of the content of autoantibodies in the blood serum of patients suffering from ACAI caused by herpes viruses using the ELISA method (Immunodot) is a highly specific screening method that can allow for an objective assessment of the dynamics of the autoimmune process, as well as control the effectiveness of the ongoing complex antiviral and immunomodulatory therapy. The detection of autoantibodies of various specificity in the blood serum of patients suffering from an atypical chronic active infection caused by herpes viruses (ACAI) is an early diagnostic marker, necessary, first of all, to identify autoimmune pathology of the nervous system, which is associated with a long course of the active mixed herpes-viral process.

Emerging Oncogenic Viruses in Head and Neck Cancers from Romanian Patients

(1) Background: Head and neck squamous cell carcinomas (HNSCCs) are some of the most frequent malignancies globally. Oncogenic viruses MCPyV, EBV and HPVs are recognized to be related to HNSCCs and skin cancers. There are no data from Romania regarding the involvement of herpes viruses and polyomaviruses in these types of cancer. We aim to evaluate the association of oncogenic viruses from Papillomaviridae, Herpesviridae, and Polyomaviridae families in HNSCCs and skin cancers. (2) Methods: A total of 26 fresh tumors (6/26 women) were tested for 67 viral agents using a multiplex PCR genotyping assay. (3) Results: A total of 23/26 (88.5%) samples were positive for one or more viruses. All the tested tumors were negative for any HPV (alpha or beta types). In total, we detected as positive samples: 16 (61.63%) EBV1, 12 (46.15%) HHV7, 8 (30.76%) MCV, 6 (23.07%) CMV and HHV6, 2 (7.69%) HHV8, 1 (3.8%) HPyV6 and EBV2. (4) Conclusions: We detected HPV-negative cases that are HPyV and HHV positive. In these fractions of HPV-negative HNSCCs cases, other oncogenic viruses may be involved, such as EBV1, MCV or CMV. Additional research is required for clarifying the natural history of these viruses in HNSCCs, as virus detection would have a decisive impact on diagnostic and decisional algorithms.

Detection and Quantification of EBV, CMV and HHV-6 DNA in Stomach Frozen Tissue of Gastritis and Gastric Cancer Patients

BackgroundHuman herpes viruses (HHVs) are among the most common infectious agents detected in the gastrointestinal tract that might be involved in oncogenesis and other gastrointestinal disorders. Although the link between the EBV and gastric cancer (GC) has been established, role of the viruses in various stomach diseases remain unknown. MethodsThe frequencies and viral copy number of EBV, CMV and HHV-6 among 50 GC tumors and 105 gastritis tissues were measured by quantitative real-time PCR.ResultsEBV, CMV and HHV-6 DNA were detected in 30 (60%), 7 (14%) and 9 (18%) of the tumor specimens, while in gastritis patients were 20 (19%), 13 (12.3%) and 16 (15.2%) respectively. The EBV frequency was significantly higher in GC compared with gastritis patients (p<0.0001). Viral load in both GC and gastritis groups was higher in either tumor or gastritis lesion compared with matched adjacent normal tissue. This study showed a clear association between GC with both EBV (p=0.0268) and CMV (p=0.0012). In addition, analyzes revealed a strong association between the EBV, CMV and HHV-6 with gastritis (p=0.0026, p <0.0001 and p=0.0405 respectively). ConclusionsOur results suggest that these three viruses might contribute to induction and development the gastritis and GC.

Association of Dementia Human Leukocyte Antigen (HLA) Profile with Human Herpes Viruses 3 and 7: An in-silico Investigation

Human leukocyte antigen (HLA), the most highly polymorphic region of the human genome, is increasingly recognized as an important genetic contributor to dementia risk and resilience. HLA is involved in protection against foreign antigens including human herpes viruses (HHV), which have been widely implicated in dementia. Here we used an in silico approach1 to determine binding affinities of glycoproteins from 9 human herpes virus (HHV) strains to 113 HLA alleles, and to examine the association of a previously identified HLA-dementia risk profile2 to those affinities. We found a highly significant correlation between high binding affinities of HLA alleles to HHV 3 and 7 and the dementia risk scores of those alleles, such that the higher the estimated binding affinity, the lower the dementia risk score. These findings suggest that protection conferred by HLA alleles may be related to their ability to bind and eliminate HHV3 and HHV7 and point to the possibility that protection against these viruses may reduce dementia incidence.

ASSESSMENT OF THE PREVALENCE OF HERPETIC INFECTION IN PATIENTS WITH ISCHEMIC HEART DISEASE

Сердечно-сосудистые заболевания в настоящее время являются ведущей причиной смерти в промышленно развитых странах. В настоящее время существует большой список инфекций, которые либо связаны с развитием атеросклероза, либо повышают риск развития сердечно-сосудистых заболеваний. Большое внимание в этом списке уделяется вирусам герпеса человека. Целью исследования явилось изучение распространенности герпесвирусной инфекции у больных с различной степенью тяжести коронарного атеросклероза. Материалы и методы: всем пациентам было проведено клиническое обследование, коронарография с расчетом индекса Gensini: GS0 (0 баллов) - 52 пациента, GS1 (1-15 баллов) - 54 пациента; GS2 (> 15 баллов) - 68 пациентов. Наличие вирусов герпеса (типы 1,2,4,5,6) определяли методом ПЦР с детекцией в реальном времени. Результаты исследования: в 15% случаев в группе GS0 был обнаружен ВПГ 1-го типа и в 10% случаев - вирус герпеса 2-го типа. В группе GS1 наблюдалась аналогичная тенденция: в 14% и 17% случаев были выявлены ВПГ 1-го и 2-го типов. У пациентов из группы GS2 ВПГ 6-го типа был выявлен в 35% случаев, а смешанная инфекция (ВПГ 1-го, 2-го и 6-го типов) - в 15% случаев. Вирус Эпштейна-Барра и цитомегаловирус не были идентифицированы ни у одного пациента. Корреляционный анализ установил прямую связь между наличием ВПГ 6-го типа и индексом Gensini (r=0,496, р=0,0002). Заключение: с увеличением тяжести коронарного атеросклероза отмечалось увеличение вирусной нагрузки. Среди пациентов со значительным коронарным атеросклерозом чаще встречается ВПГ 6-го типа и выявляется смешанная герпесвирусная инфекция, что требует дальнейшего изучения Cardiovascular diseases are currently the leading cause of death in industrialized countries. Currently, there is a large list of infections that are either associated with the development of atherosclerosis, or increase the risk of developing cardiovascular diseases. Much attention in this list is paid to human herpes viruses. The aim of the study was to study the prevalence of herpesvirus infection in patients with varying degrees of severity of coronary atherosclerosis. Materials and methods: all patients underwent a clinical examination, coronary angiography with the calculation of the Gensini index: GS0 (0 points) - 52 patients, GS1 (1-15 points) - 54 patients; GS2 (>15 points) - 68 patients. The presence of herpes viruses (types 1,2,4,5,6) was determined by real-time PCR detection. Results of the study: in 15% of cases in the GS0 group, HSV type 1 was detected and in 10% of cases, herpes virus type 2 was detected. In the GS1 group, a similar trend was observed: in 14% and 17% of cases, HSV types 1 and 2 were detected. In patients from the GS2 group, HSV type 6 was detected in 35% of cases, and mixed infection (HSV types 1, 2 and 6) - in 15% of cases. Epstein-Barr virus and cytomegalovirus have not been identified in any patients. The correlation analysis established a direct relationship between the presence of HSV type 6 and the Gensini index (r=0.496, p=0.0002). Conclusion: with an increase in the severity of coronary atherosclerosis, there was an increase in the viral load. Among patients with significant coronary atherosclerosis, HSV type 6 is more common and mixed herpesvirus infection is detected, which requires further study

Reduced dementia incidence following varicella zoster vaccination in Wales 2013—2020

INTRODUCTION: Chronic infection with herpes viruses is a potential contributing factor to the development of dementia. The introduction of nationwide shingles (varicella zoster) vaccination in Wales might therefore be associated with reduced incident dementia. METHODS: We analyzed the association of shingles vaccination with incident dementia in Wales between 2013 and 2020 using retrospectively collected national health data. RESULTS: Vaccinated individuals were at reduced risk of dementia (adjusted hazard ratio: 0.72; 95% CI: 0.69 to 0.75). The association was not modified by a reduction in shingles diagnosis and was stronger for vascular dementia than for Alzheimers disease. Vaccination was also associated with a reduction in several other diseases and all-cause mortality. DISCUSSION: Our study shows a clear association of shingles vaccination with reduced dementia, consistent with other observational cohort studies. The association may reflect selection bias with people choosing to be vaccinated having a higher healthy life expectancy.

The Role of Herpes Viruses in Pulmonary Fibrosis

Pulmonary fibrosis (PF) is a serious lung disease which can result from known genetic or environmental exposures but is more commonly idiopathic (IPF). In familial PF (FPF), the majority of identified causal genes play key roles in the maintenance of telomeres, the protective end structures of chromosomes. Recent evidence suggests that short telomeres may also be implicated causally in a significant proportion of idiopathic cases. The possible involvement of herpes viruses in PF disease incidence and progression has been examined for many years, with some studies showing strong, statistically significant associations and others reporting no involvement. Evidence is thus polarized and remains inconclusive. Here we review the reported involvement of herpes viruses in PF in both animals and humans and present a summary of the evidence to date. We also present several possible mechanisms of action of the different herpes viruses in PF pathogenesis, including potential contributions to telomere attrition and cellular senescence. Evidence for antiviral treatment in PF is very limited but suggests a potential benefit. Further work is required to definitely answer the question of whether herpes viruses impact PF disease onset and progression and to enable the possible use of targeted antiviral treatments to improve clinical outcomes.

The Current Landscape of Oncolytic Herpes Simplex Viruses as Novel Therapies for Brain Malignancies

Despite advances in surgical resection and chemoradiation, high-grade brain tumors continue to be associated with significant morbidity/mortality. Novel therapeutic strategies and approaches are, therefore, desperately needed for patients and their families. Given the success experienced in treating multiple other forms of cancer, immunotherapy and, in particular, immunovirotherapy are at the forefront amongst novel therapeutic strategies that are currently under investigation for incurable brain tumors. Accordingly, herein, we provide a focused mini review of pertinent oncolytic herpes viruses (oHSV) that are being investigated in clinical trials.

Epidemiological Aspects of Equine Herpes Virus Infection in South Gujarat, India

Background: The equine herpes viruses (EHV) are highly infective pathogens of all members of the Equidae family worldwide. EHV-1 predominantly associated with the abortion, neonatal death, neurological diseases, whereas, EHV-4 is mostly associated with the respiratory disease, generally termed as equine rhinopneumonitis. This present investigation was planned to study sero-prevalence of EHV-1/4 infections in horses of south Gujarat, India. Methods: A total of 253 horses showing symptoms of respiratory illness or having history were screened by indirect ELISA test. While, blood samples were analysed for various haematological parameters. Effects of risk factors were studied and statistical analysis of data was done. Result: Over all prevalence of EHV-1/4 infection was 16.60% in South Gujarat, India. Effects of various risk factors (age, sex, breed, and locality) were non-significant. Means of all haematological parameters were in normal range and significant difference was not observed between sero-positive and sero-negative horses. Population of mid cells (monocytes) was found significantly higher (p less than 0.05 in sero-positive horses as compare to sero-negative horses.