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.

Clinical variants of chronic gastritis in childhood

Objective. To establish the features of various clinical variants of chronic gastritis in childhood. Material and methods. 415 children aged 617 years with chronic Hp-associated gastritis were examined. The clinical and anamnestic data, the results of laboratory, endoscopic and morphological studies of gastrobioptates were analyzed. Genetic typing of Hp was carried out with the determination of 16 pathogenicity factors. The persistence of human herpes viruses of types 6 and 8 and Epstein Barr viruses in the gastric mucosa was determined. Results. The clinical heterogeneity of chronic gastritis in children with the allocation of four topical variants was established: isolated duodenitis, duodenogastritis, antrum gastritis, pangastritis. It was found that with the first two, a high frequency of giardiasis is registered, with antrumgastritis and especially pangastritis, a significant contamination of the gastric mucosa with Hp is detected, mainly of CagA and VacA-positive strains. It is proved that the persistence of the type 6 human herpes virus does not affect the severity of inflammation, while the presence of the Epstein-Barr virus increases it. Colonization of the gastric mucosa by highly pathogenic Hp strains significantly increases the severity and activity of inflammation. It is shown that atrophy of the gastric mucosa in children is uncertain, and true atrophic gastritis occurs only in 0.61 % of cases. Conclusions. Chronic gastritis in children is a heterogeneous pathology, and its individual variants differ significantly in etiological factors including infectious, pathogenetic mechanisms and features of the morphology of gastric mucosa. This should be taken into account when carrying out medical support for patients.

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.

Molecular Detection of Human Herpes Viruses in Suspected Measles Serum Samples from Senegal, 2014 to 2017

Herpesviruses are known to cause a diversity of clinical syndromes, ranging from minor cutaneous lesions to life-threatening illnesses, especially in immunocompromised hosts. Here, we investigate retrospectively the contribution of five human herpesviruses, including herpes simplex virus Cytomegalovirus (CMV), the Epstein–Barr virus (EBV), human herpesvirus 6, and varicella zoster virus (VZV) in serum samples collected from measles suspected patients with at least fever and rash. Sera specimens were first tested for serological evidence of measles and rubella virus infection by ELISA, and DNA extracted from an aliquot of each clinical specimen for molecular detection of human herpes viruses by RT-qPCR. A total of 3,358 specimens have been collected and tested for herpes viruses. Nearly half of the overall suspected cases were children younger than 5 years (49.4%). Of the 3,358 sera tested by ELISA, 227 (6.7%) were measles laboratory confirmed and 152 (4.5%) rubella laboratory confirmed. Herpes viruses were detected in 1763 (52.5%), and VZV was the most common with 44.3%, followed by EBV with 10.7%. Coinfections were found in 352 (20%) cases, and the most common co-detections were VZV/EBV or VZV/CMV (169 and 81 cases, respectively). A clear seasonal pattern of VZV, EBV, and CMV identification was observed, with the highest incidence between February and April each year. Results of this investigation provide more insights into cutaneous rash syndrome etiologies in patients sampled in the framework of measles/rubella surveillance in Senegal, which is useful for the guidance of both case definition revision and clinical practice as well as for public health policy.

Salivary DNA loads for human herpes viruses 6 and 7 are correlated with disease phenotype in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex chronic condition affecting multiple body systems, with unknown cause, unclear pathogenesis mechanisms, and fluctuating symptoms which may lead to severe debilitation. It is frequently reported to have been triggered by an infection, particularly with herpes virus family members; however, there are no clear differences in exposure to, or seroprevalence of, any herpes virus in people with ME/CFS and healthy individuals. Herpes viruses exist in lytic and latent forms, and it is possible that ME/CFS is associated with viral reactivation, which has not been detectable previously due to insensitive testing methods.Saliva samples were collected from 30 people living with ME/CFS at monthly intervals for six months and at times when they experienced symptom exacerbation, as well as from 14 healthy control individuals. The viral DNA load of the nine human herpes viruses was determined by digital droplet PCR. Symptoms were assessed by questionnaire at each time point.Human herpes virus (HHV) 6B, HHV-7, herpes simplex virus 1 and Epstein Barr virus were detectable within the saliva samples, with higher HHV-6B and HHV-7 viral loads detected in people with ME/CFS than in healthy controls. Participants with ME/CFS could be broadly separated into two groups: one group displayed fluctuating patterns of herpes viruses detectable across the six months while the second group displayed more stable viral presentation. In the first group, there was positive correlation between HHV-6B and HHV-7 viral load and severity of symptom scores, including pain, neurocognition and autonomic dysfunction.The results indicate that fluctuating viral load, related to herpesvirus reactivation state, may play a role in ME/CFS pathogenesis, or might be a consequence of dysregulated immune function. The sampling strategy and molecular tools developed permit large-scale epidemiological investigations.Contribution to the FieldThe cause of ME/CFS and the mechanisms underlying disease pathogenesis are not known, although symptoms are often triggered by infection. Human herpes virus (HHV) family members have been implicated, although there is no difference in the seroprevalence of any HHV in people with ME/CFS and healthy controls, showing there is similar prior infection rate. HHVs exist in either latent or active, lytic, phases in the human host, and it is possible that ME/CFS symptoms and their severity is related to HHV reactivation from a latent state. We have used droplet digital PCR, a sensitive and specific method, to measure the prevalence and DNA concentration of HHVs in the saliva of people with ME/CFS and controls, and analysed the correlation with disease over a six-month timecourse. We found that two HHVs, HHV-7 and HHV-6B, were elevated in saliva from people with ME/CFS, and that in people who were severely affected by ME/CFS, the concentration HHV DNA correlated with symptom severity over time in a subgroup of patients with fluctuating salivary HHV repertoire. Our study demonstrates the feasibility of measuring HHV concentration in readily acquired samples, enabling future large-scale studies aimed at testing the causal role of HHV reactivation in ME/CFS disease.

Herpesvirus and inflammatory bowel disease

Aim. Conduct a review of studies characterizing the role of herpesvirus infections in the pathogenesis of inflammatory bowel disease (IBD).Introduction. The study of the role of herpes virus infections in the pathogenesis of inflammatory bowel disease (IBD) is currently of considerable interest to researchers from different countries.Result. The results of studies on the significance of human herpes viruses (HHV) in inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD), their effect on the course of these diseases, and refractory treatment of UC and CD in the presence of HHV are presented.It is shown that most researchers unanimously conclude that the main attention should be paid to Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpes simplex virus type 6 (HHV-6), which are found in the mucous membrane of the colon in patients with IBD and affect both the course of the disease and the effectiveness of the treatment. Attention is focused on the fact that it is necessary to differentiate colitis due to HHV and IBD, proceeding against the background of HHV reactivation, since approaches to the treatment of these conditions are different.Conclusion. Requires targeted research on the role of human herpes viruses in the pathogenesis of IBD.

Herpes Infections in Suspected Cases of Yellow Fever in the Democratic Republic of the Congo

In the battle to quickly identify potential yellow fever arbovirus outbreaks in the Democratic Republic of the Congo, active surveillance of acute febrile jaundice patients across the country is a powerful tool. However, patients who test negative for yellow fever virus infection are too often left without a diagnosis. By retroactively screening samples for other potential viral infections, we can both try to find sources of patient disease and also gain information on how commonly they circulate in the population. Here, we assessed the prevalence of human herpes viruses (HHVs) in these acute febrile jaundice disease samples. We found 22.6% had active HHV replication, and that over half were characterized by co-infection either among HHVs or between HHVs and other viral infections previously identified. Our results show that the role of HHV primary infection or reactivation in contributing to acute febrile jaundice disease should be further investigated.

Kissing, Saliva and Human Papilloma Virus: Principles, Practices, and Prophylaxis

Introduction: Kissing is a globally practiced form of communication, yet saliva is often deemed a harmless bodily fluid. Many viruses thrive in salivary and oro-pharyngeal lymphoid cells. These viruses include Human Papilloma Virus (HPV), Human Herpes Viruses, Epstein –Barr, HIV, Polio and others, and are transmitted between people when kissing. Aim: This appraisal (1)assesses socially sanctioned kissing habits, (2) examines the presence of Human Papilloma Virus [HPV] in saliva and salivary tests for HPV, (3) reviews protection from HPV vaccines, (4)deconstructs attitudes and behavior, and critiques the oncogenic potential of HPV morbidity from peri-osculation practices. Materials and Methods: Clinical- tests for putative HPV viruses in oro-pharyngeal cancers use saliva to detect HPV oncogenic types; these re-affirm presence of HPV’s in saliva, and their causal relationship to the majority of head and neck cancers. Conclusion: Although frequency of new infections from kissing is unknown, this critique suggests caution against random kissing, encourages use of HPV vaccination for prophylaxis, and indicates that this may moderate HPV and viral transmission, with consequent reduction of HPV morbidity and mortality.