Human Herpesvirus 6 Infection Research Articles

The HHV-6A Proteins U20 and U21 Target NKG2D Ligands to Escape Immune Recognition.

The coevolution of the human immune system and herpesviruses led to the emergence and diversification of both cellular danger molecules recognized by immune cells on the one hand and viral countermeasures that prevent the expression of these proteins on infected cells on the other. There are eight ligands for the activating receptor NKG2D in humans – MICA, MICB, ULBP1-6. Several of them are induced and surface-expressed on herpesvirus-infected cells to serve as danger signals to activate the immune system. Therefore, these ligands are frequently targeted for suppression by viral immune evasion mechanisms. Mechanisms to downregulate NKG2D ligands and thereby escape immune recognition have been identified in all other human herpesviruses (HHV), except for HHV-6A. In this study, we identify two HHV-6A encoded immunoevasins, U20 and U21, which suppress the expression of the NKG2D ligands ULBP1 and ULBP3, respectively, during infection. Additionally, MICB is targeted by a so far unexplored viral protein. Due to the diminished NKG2D ligand surface expression on infected cells, recognition of HHV-6A infected cells by innate immune cells is impaired. Importantly, our study indicates that immune escape mechanisms between the related herpesviruses HHV-6A and HHV-6B are evolutionary conserved as the same NKG2D ligands are targeted. Our data contribute an additional piece of evidence for the importance of the NKG2D receptor – NKG2D ligand axis during human herpesvirus infections and sheds light on immune evasion mechanisms of HHV-6A.

Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain.

Both chronic alcoholism and human herpesvirus-6 (HHV-6) infection have been identified as promoters of neuroinflammation and known to cause movement-related disorders. Substantia Nigra (SN), the dopaminergic neuron-rich region of the basal ganglia, is involved in regulating motor function and the reward system. Hence, we hypothesize the presence of possible synergism between alcoholism and HHV-6 infection in the SN region and report a comprehensive quantification and characterization of microglial functions and morphology in postmortem brain tissue from 44 healthy, age-matched alcoholics and chronic alcoholics. A decrease in the perivascular CD68+ microglia in alcoholics was noted in both the gray and white matter. Additionally, the CD68+/Iba1− microglial subpopulation was found to be the dominant type in the controls. Conversely, in alcoholics, dystrophic changes in microglia were seen with a significant increase in Iba1 expression and perivascular to diffuse migration. An increase in CD11b expression was noted in alcoholics, with the Iba1+/CD11b− subtype promoting inflammation. All the controls were found to be negative for HHV-6 whilst the alcoholics demonstrated HHV-6 positivity in both gray and white matter. Amongst HHV-6 positive alcoholics, all the above-mentioned changes were found to be heightened when compared with HHV-6 negative alcoholics, thereby highlighting the compounding relationship between alcoholism and HHV-6 infection that promotes microglia-mediated neuroinflammation.

Seroprevalence of Human Herpesvirus Infections in Newly Diagnosed HIV-Infected Key Populations in Dar es Salaam, Tanzania.

Background Human herpesvirus (HHV) infections can significantly increase the risk of human immunodeficiency virus (HIV) transmission and accelerate disease progression. In the population at high risk of HIV infection, also termed as key populations (female sex workers (FSW), men who have sex with men (MSM), and people who inject drugs (PWID)), and their sexual partners, HHV infections can potentially compromise the efforts to prevent and control HIV infection. Here, we investigated the seroprevalence of HHV infections among HIV-infected key populations in Dar es Salaam, Tanzania. Methodology. We analyzed 262 archived serum samples of HIV-infected key populations from the integrated biobehavioral surveillance (IBBS) study conducted in Dar es Salaam, Tanzania. The enzyme-linked immunosorbent assay was used to determine IgG and IgM titers for cytomegalovirus (CMV) and herpes simplex virus (HSV) types 1 and 2. Results The overall seropositivity of HHV IgG was 92% (95% CI: 87.7–95.3%). HHV IgM was not detected in any of the samples. The most seroprevalent coinfection was CMV at 69.1% (181/262), followed by HSV-2 33.2% (87/262) and HSV-1 32.1% (84/262). HSV-2 infection differed by key population groups; it accounted for FSW (46.3%) (p=0.0001) compared to PWID (21.6%) and MSM (22.7%). In contrast, seroprevalence for CMV and HSV-1 was comparable across the key population groups; whereby, CMV was 62%, 75.3%, and 75% and HSV-1 was 26.4%, 39.2%, and 31.8% for FSW, MSM, and PWID, respectively. We also observed that multiple coinfections with CMV-HSV-2 (p=0.042) and CMV-HSV-1-HSV-2 (p=0.006) were significantly associated with key population aged above 40 years. Conclusion The IgG seroprevalence of CMV, HSV-1, and HSV-2 was high among HIV-positive key populations. These findings indicate that these individuals are prone to recurrence of HHV infections and may harbor replicating viruses that subsequently may affect HIV disease progression. Therefore, this warrants concerted efforts for integrated HIV and sexually transmitted infection prevention programs targeting key populations.

Molecular Detection and Genotyping of Human Herpes Virus 8 in a sample of Iraqi Blood Donors

Human herpes virus-8 (HHV-8) infection has increased recently in Arabic countries. HHV-8 in healthy persons does not necessarily cause life-threatening infection, and however, it causes a more severe infection among immunocompromised patients. The distribution of HHV-8 genotypes varies according to ethnicity and depends on the geographic region prior rapid development of global travel. A cross sectional prospective study included a hundred healthy blood donor samples with a mean age of (36.60±10.381), 81% were positive for molecular detection of HHV-8 DNA. PCR results for HHV-8 were strongly related with risk factors such as the number of sexual relations, previous surgeries, blood transfusion, dental operation, and the number of blood donations. In this study, genotypes (A, B, C and D) were detected, largely associated with blood donors residences and distributed to areas of Iraq through a map. Genotype A comprised 28 (34.6%) of blood donors and for genotype C it was 16 (19.8%) and both genotypes were found to be the predominant genotypes, followed by genotype B of 7 (8.7%) and D of 2 (2.5%), the latter is included into Mixed genotypes of 8 (9.9%), whereas, 22 (27.2%) were undetermined genotypes. Efforts should focus on these findings, which may indicate that Iraq is an endemic region of HHV-8 infection.

Retrohepatic Mass: A Case of Human Herpesvirus-8 Negative Multicentric Castleman’s Disease

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder with aggressive systemic presentation and poor prognosis. Here, we present a case of MCD in a 37-year-old Asian American woman with a past medical history of the polycystic ovarian syndrome (PCOS), human papilloma virus (HPV), herpes simplex virus-1 (HSV-1), iron deficiency, and vitamin B12 deficiency-related anemia. The patient underwent surgical resection with good recovery. Hemoglobin and erythrocyte sedimentation rate (ESR) normalized after surgical resection. Although the influence of risk factors such as human immunodeficiency virus (HIV) or human herpesvirus-8 (HHV-8) infections on MCD relapse are not well understood, patient education on MCD risk factors is important, as they may place the patient at greater risk for recurrence. MCD should be considered in patients with chronic inflammation and a mass on imaging.

Hemophagocytic lymphohistiocytosis occurring after liver transplantation: A case series and review of the literature.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by excessive inflammation and tissue destruction due to a dysregulated immune response. Its secondary form is most commonly triggered by viral infection or malignancy. There have previously been 11 cases of acquired HLH described following liver transplantation in adult transplant recipients, most occurring within the first year following transplantation. Herein, we describe two cases of HLH in liver transplant recipients that both occurred remotely following transplantation. In the first case, HLH was thought to be triggered by the development of a post-transplant lymphoproliferative disorder in a patient who was initially diagnosed with recurrent autoimmune hepatitis. In the second, it was thought to be triggered by a newly acquired human herpesvirus-8 infection. In both cases, the syndrome was not recognized until treatment for the initial putative diagnoses was unsuccessful. Despite treatment, both patients unfortunately died from multiorgan failure. HLH in the post-liver transplant setting is likely under-recognized and has a high mortality; early diagnosis and intervention may lead to improved outcomes.

Human Herpes-Virus 6 Infection in Immunocompromised Patients after Chemotherapy and Autologous Stem Cell Transplantation

Introduction.The ubiquitous spreading of human herpes viruses (HHV) in nature, the variety of ways and methods of their transmission, ability of lifelong persistence in the host and pantropism lead to almost total infection of the adult population. In immunocompromised patients (pts) with blood system diseases HHV infections are characterized by severe complications and may cause death without proper diagnostics and treatment. HHV-6 is widely explored in pts after allogenic transplantation but its role in pts after chemotherapy (ChT) courses and autologous stem cell transplantation (ASCT) is not investigated enough.Aims. To determine the rate of HHV-6 reactivation in pts with hematological diseases. To investigate the role of HHV-6 infection in pts with immunodeficiency after ChT and ASCT to define treatment tactics.Methods. From January 2013 to July 2017 in hematology department of National Research Center retrospectively analyzed 273 pts with newly diagnosed hematology diseases (72-with acute lymphoblastic leukemia (ALL), 141 - acute myeloblastic leukemia (AML), 15-with high-grade B-cell lymphoma (BCL), 45 - aplastic anemia (AA). ALL was treated according to ALL 2009 protocol, AML - with standart «7+3» ChT, AA - with Antithymocyte Globulin or cyclosporine, BCLs - with R-EPOCH/R-HMA or R-EPOCH. We performed real time polymerase chain reaction (RT-PCR) for detecting HHV-6 DNA in cases of any clinical complication after ChT, in period of febrile neutropenia and post-transplant. The investigation included the samples of blood, cerebrospinal fluid, urine, feces, bone marrow, bronchoalveolar lavage (BAL), saliva, pulmonary effusion. Diagnostically significant criterion was the DNA detection of more than 500 copies/ml.Results. HHV-6 reactivation was detected in 90 pts out of 273 (32,9%): 38% in AML pts (54 out of 141), 33% - in ALL pts (24 out of 72), in group of AA - 15,5% (7 out of 45), BCL - in 5 pts (33%). Twenty-five pts (19 with ALL, 6 - BCL) underwent ASCT. HHV-6 DNA was revealed in 44% cases of pts after ASCT, but only 24% of these pts received antiviral therapy because they had clinical symptoms of HHV-6 infection. The most severe infection was encephalitis. Among AML pts after ChT, manifestations of HHV-6 infections were detected in 14 out of 141 (10%), among ALL without ASCT- in 9,4% (5 out of 53). Before stating the HHV-6 infection and starting special treatment all other reasons of complications were excluded (bacterial and fungal). All pts with clinical symptoms of viral contagion received iv ganciclovir (10mg/kg/day) with further prophylaxis of valganciclovir (900mg/day) during 2-9 weeks. Almost all clinical symptoms regressed after 3-5 days of the treatment but DNA copies in samples stayed much longer (2-6 weeks) and early stop of treatment (1-2 weeks) in some cases caused the increasing of HHV-6 copies. Interestingly, that pts with AA didn't have clinical symptoms though had reactivation of HHV-6 and nobody of them needed antiviral treatment.Conclusion. HHV-6 reactivation is quite common in immunocompromised pts (see table 1) but development of HHV- 6 infection requires treatment only in 9,5% (26 pts out of 273) of them (including pts after ASCT). The most severe complications associated with HHV-6 included encephalitis, enteropathy, urinary infection and pneumonia. More frequently HHV-6 was detected in blood samples and feces.The HHV-6 infection needs to be diagnosed when bacterial and fungal infections are excluded. In case without clinical symptoms there is no need to start specific treatment. When stated, HHV-6 infection requires continual antiviral curing until complete disappearing of DNA copies from biological liquids. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Late-onset intrauterine growth restriction and HHV-6 infection: A pilot study.

Late-onset Intrauterine growth restriction (IUGR) refers to impaired growth and development of the fetus, characterized by placental morphological abnormalities that affect the fetus's supply of nutrients. Human leukocyte antigen-G (HLA-G) is physiologically expressed during pregnancy, but decreased in normal placenta during the last weeks of gestation possibly inducing childbirth. Several viruses involved in congenital infection, such as herpesviruses, exploit HLA-G expression as an immune-escape mechanism. To date, despite different congenital herpetic infections havingbeen associated with late IUGR, no direct implication of Human herpesvirus 6 (HHV-6) infection has been reported. We evaluated HLA-G expression and HHV-6 infection in 11 placentas from late-onset IUGR newborns and 11 placentas from uncomplicated pregnancies by histopathological and immunohistochemistry analysis. We found higher levels of HLA-G expression and HHV-6 presence in IUGR placenta samples compared with control placenta samples. We report HHV-6 staining in IUGR placenta samples, characterized by high HLA-G expression. These preliminary data suggest a possible involvement of HHV-6 infection in HLA-G deregulation that might affect vessel remodeling and prevent the correct pregnancy outcome in the IUGR condition.

Human Herpesvirus 6 Infection and Risk of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis

Introduction: Chronic fatigue syndrome (CFS) is a neurological disease that is accompanied by excessive fatigue or tiredness. There are several reports confirming the association between human herpesvirus 6 (HHV-6) infection and CFS illness. This systematic review and meta-analysis was performed to integrate the information of published studies with regard to this association until May 2021. Methods: The literature search was based on keywords including “chronic fatigue syndrome and HHV 6,” “chronic fatigue syndrome and HHV-6,” “chronic fatigue syndrome and HHV6,” “chronic fatigue syndrome and Herpes virus 6,” and “chronic fatigue syndrome and Herpesvirus6” in MEDLINE (PubMed), Web of Science, and EMBASE. Results: The literature search identified 17 studies to be included in the systematic review and 11 studies in meta-analysis. The symmetry funnel plot and Egger’s test (p value = 0.2) identified no publication bias among studies. Moreover, the low level of I² revealed homogeneity across studies. Discussion: In conclusion, the association between the HHV-6 infection and CFS incidence was substantiated. However, the results of this study also suggest that further comprehensive studies are needed to solidify the association between HHV-6 and CFS. Future studies should consider additional factors that may have affected the significance of such a correlation.

Berberine in Human Oncogenic Herpesvirus Infections and Their Linked Cancers.

Human herpesviruses are known to induce a broad spectrum of diseases, ranging from common cold sores to cancer, and infections with some types of these viruses, known as human oncogenic herpesviruses (HOHVs), can cause cancer. Challenges with viral latency, recurrent infections, and drug resistance have generated the need for finding new drugs with the ability to overcome these barriers. Berberine (BBR), a naturally occurring alkaloid, is known for its multiple biological activities, including antiviral and anticancer effects. This paper comprehensively compiles all studies that have featured anti-HOHV properties of BBR along with promising preventive effects against the associated cancers. The mechanisms and pathways induced by BBR via targeting the herpesvirus life cycle and the pathogenesis of the linked malignancies are reviewed. Approaches to enhance the therapeutic efficacy of BBR and its use in clinical practice as an anti-herpesvirus drug are also discussed.

Hemolytic uremic syndrome related to Shiga-like toxin-producing Escherichia coli with encephalitis hiding a human herpesvirus-6 infection: a case report

BackgroundCardiac and neurological involvement in hemolytic uremic syndrome are life-threatening complications. The most frequent complications of cardiac involvement in hemolytic uremic syndrome are myocarditis and cardiac dysfunction due to fluid overload. Pericarditis remains very rare in hemolytic uremic syndrome. To our knowledge, only five cases of cardiac tamponade associated with hemolytic uremic syndrome have been described in literature.Case summaryA 27-month-old Caucasian girl presented with symptoms of nonbloody diarrhea and tonic-clonic seizures. The diagnosis of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome with central nervous system involvement was made, and stool examination revealed infection with a Shiga-like toxin-producing Escherichia coli. She did not need renal replacement therapy but had severe neurological impairment. The patient’s course was complicated by pericardial effusion. A pericardiocentesis was performed via an apical approach because the pericardial effusion was predominantly surrounding the left ventricle. Effusion analysis showed an exudate and positivity for human herpesvirus-6B on polymerase chain reaction with viremia. This finding was consistent with primary human herpesvirus-6 infection with encephalitis.ConclusionWe report this uncommon case of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome associated with a severe human herpesvirus-6 infection. Secondary isolated pericardial effusion and atypical neurological involvement are uncommon in Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome and should lead the physician to perform additional investigations.

POS1353 SERUM PROTEOMICS REVEALS INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS-1 AS BIOMARKERS FOR IDIOPATHIC MULTICENTRIC CASTLEMAN’S DISEASE

Background:Castleman’s disease (CD) is a lymphoproliferative disorder1 and presents as two distinct clinical entities: the localized form, unicentric CD (UCD) and the multicentric form, multicentric CD (MCD)2. MCD without human herpesvirus-8 (HHV-8) infection is defined idiopathic MCD (iMCD)3 and most MCDs in Japan are iMCDs. TAFRO syndrome is a group of disease that present with T: thrombocytopenia, A: anasarca, F: fever, R: reticulin fibrosis/renal dysfunction, O: organomegaly4. iMCD-TAFRO is present in the TAFRO syndrome and it is thought that pathology of lymph node biopsy shows an MCD-like appearance, and some clinical features overlap with MCD5. That do not belong to any of the above categories is classified as iMCD-not otherwise specified (iMCD-NOS). No biomarkers stratifying iMCD-NOS and iMCD-TAFRO have been identified, and no biomarkers defining treatment response have been identified for iMCD.Objectives:We will identify biomarkers that discriminate iMCD-NOS and iMCD-TAFRO or predict the treatment responsiveness.Methods:We performed a comprehensive analysis of serum proteins using the L-Series Human Antibody Array L-507 on the 4 iMCD-NOS and 2 iMCD-TAFRO patients from which pre- and post-tocilizumab treatment samples were obtained. An analysis by L-507 identified insulin-like growth factor binding proteins-1 (IGFBP-1) as a protein with a high rate of reduction post treatment. Sera from 28 healthy controls, 8 patients with iMCD-NOS, and 6 patients with iMCD-TAFRO were used to validate IGFBP-1 by ELISA. The mean ages of healthy controls, iMCD-NOS, and iMCD-TAFRO used in the validation ELISA were 50, 56, and 47 years, respectively, with no significant differences among the groups. The ratio of male to female was almost 1:1.Results:The 4 patients who responded well to treatment with tocilizumab all had a high rate of IGFBP-1 reduction by L-507 serum protein arrays. In ELISA, serum IGFBP-1 was significantly higher (p=0.0016) before the introduction of treatment in iMCD patients than healthy controls. In addition, serum IGFBP-1 level of iMCD-TAFRO was significantly higher than iMCD-NOS (p=0.024). Furthermore, post-treatment serum IGFBP-1 was decreased in many cases.Conclusion:Serum IGFBP-1 may play a particularly important role in the pathogenesis of iMCD-TAFRO and may be useful in discriminating between iMCD-NOS and iMCD-TAFRO. In the future, we will accumulate more cases, compare it with other inflammatory diseases, and examine the difference in response to treatment.

Cox4i2 Triggers an Increase in Reactive Oxygen Species, Leading to Ferroptosis and Apoptosis in HHV7 Infected Schwann Cells.

Emerging evidence suggests that reactive oxygen species (ROS) play a significant role in the pathogenesis of peripheral nerve damage. Our previous study indicated that human herpesvirus 7 (HHV7) induces Bell’s palsy. However, the specific mechanism underlying the effects of ROS in HHV7 infection-induced facial nerve damage is unknown. In this study, we established a rat FN model by inoculating an HHV7 virus solution. The facial grading score and LuxolFastBlue (LFB) staining were used to assess the success of the model. Using mRNA-sequencing analysis, we found that the expression of Complex IV Subunit 4 Isoform 2 (Cox4i2) increased in infected Schwann cells (SCs). Cox4i2 was suggested to increase COX activity, thereby promoting ROS production. The changes in the endogenous oxidant and antioxidant system were assessed, and the results showed that oxidative stress increased after HHV7 infection in vivo and in vitro. However, we found that oxidative injury was relieved after the transfection of shCox4i2 in HHV7-treated SCs by evaluating cell death, cell proliferation, and the ROS level as well as the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Furthermore, we hypothesised that Cox4i2 loss would attenuate HHV7-induced ferroptosis and apoptosis, which are closely related to ROS in SCs. Our research illustrated that the knockdown of Cox4i2 suppresses HHV7-induced RSC96 cell ferroptosis as well as apoptosis via the ERK signalling pathway. Overall, several in vitro and in vivo methods were adopted in this study to reveal the new mechanism of ROS-induced and Cox4i2-mediated apoptosis and ferroptosis in HHV7 infected SCs.

Modulation of microRNome by Human Cytomegalovirus and Human Herpesvirus 6 Infection in Human Dermal Fibroblasts: Possible Significance in the Induction of Fibrosis in Systemic Sclerosis.

Human cytomegalovirus (HCMV) and Human herpesvirus 6 (HHV-6) have been reportedly suggested as triggers of the onset and/or progression of systemic sclerosis (SSc), a severe autoimmune disorder characterized by multi-organ fibrosis. The etiology and pathogenesis of SSc are still largely unknown but virological and immunological observations support a role for these beta-herpesviruses, and we recently observed a direct impact of HCMV and HHV-6 infection on the expression of cell factors associated with fibrosis at the cell level. Since miRNA expression has been found profoundly deregulated at the tissue level, here we aimed to investigate the impact on cell microRNome (miRNome) of HCMV and HHV-6 infection in in vitro infected primary human dermal fibroblasts, which represent one of the main SSc target cells. The analysis, performed by Taqman arrays detecting and quantifying 754 microRNAs (miRNAs), showed that both herpesviruses significantly modulated miRNA expression in infected cells, with evident early and late effects and deep modulation (>10 fold) of >40 miRNAs at each time post infection, including those previously recognized for their key function in fibrosis. The correlation between these in vitro results with in vivo observations is strongly suggestive of a role of HCMV and/or HHV-6 in the multistep pathogenesis of fibrosis in SSc and in the induction of fibrosis-signaling pathways finally leading to tissue fibrosis. The identification of specific miRNAs may open the way to their use as biomarkers for SSc diagnosis, assessment of disease progression and possible antifibrotic therapies.

Symmetric blaschkoid pityriasis rosea in a child.

Pityriasis rosea (PR) is a common papulosquamous disorder that may be related to primary infection or endogenous reactivation of human herpesvirus 7 and 6. Based on morphology, distribution, and size of lesions, several atypical variants of PR have been described. PR following the lines of Blaschko represents an atypical variant that has seldom been described in the literature. Here, we describe a child with diabetes who developed PR in a symmetrical, blaschkolinear configuration.

Structures and Divergent Mechanisms in Capsid Maturation and Stabilization Following Genome Packaging of Human Cytomegalovirus and Herpesviruses.

Herpesviruses are the causative agents of several diseases. Infections are generally mild or asymptomatic in immunocompetent individuals. In contrast, herpesvirus infections continue to contribute to significant morbidity and mortality in immunocompromised patients. Few drugs are available for the treatment of human herpesvirus infections, mainly targeting the viral DNA polymerase. Moreover, no successful therapeutic options are available for the Epstein–Barr virus or human herpesvirus 8. Most licensed drugs share the same mechanism of action of targeting the viral polymerase and thus blocking DNA polymerization. Resistances to antiviral drugs have been observed for human cytomegalovirus, herpes simplex virus and varicella-zoster virus. A new terminase inhibitor, letermovir, recently proved effective against human cytomegalovirus. However, the letermovir has no significant activity against other herpesviruses. New antivirals targeting other replication steps, such as capsid maturation or DNA packaging, and inducing fewer adverse effects are therefore needed. Targeting capsid assembly or DNA packaging provides additional options for the development of new drugs. In this review, we summarize recent findings on capsid assembly and DNA packaging. We also described what is known about the structure and function of capsid and terminase proteins to identify novels targets for the development of new therapeutic options.

Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways.

Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechanisms of action might be an effective way to defeat challenges that hurdle the progress of anti-herpesvirus drug development, including the problems with drug resistance and recurrent infections. Therefore, in this review, we aim to hunt down all investigations that feature the curative properties of curcumin, a principal bioactive phenolic compound of the spice turmeric, in regard to various human and animal herpesvirus infections and inflammation connected with these diseases. Curcumin was explored with potent antiherpetic actions against herpes simplex virus type 1 and type 2, human cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus, Epstein–Barr virus, bovine herpesvirus 1, and pseudorabies virus. The mechanisms and pathways by which curcumin inhibits anti-herpesvirus activities by targeting multiple steps in herpesvirus life/infectious cycle are emphasized. Improved strategies to overcome bioavailability challenges that limit its use in clinical practice, along with approaches and new directions to enhance the anti-herpesvirus efficacy of this compound, are also reviewed. According to the reviewed studies, this paper presents curcumin as a promising natural drug for the prevention and treatment of herpesvirus infections and their associated inflammatory diseases.

Molecular Detection of Human Herpes Virus-8 in Prostatic Adenocarcinoma and Benign Prostatic Hyperplasia Tissues by DNA -In Situ Hybridization

Human Herpes Virus-8 (HHV-8) is a sexually transmitted viral infection that can infect the prostate epithelium in immunocompromised adults. Recently, HHV-8 was related to the development and progression of several human malignancies like prostatic adenocarcinoma. This retrospective research was designed to analyze the distribution and possible impact of HHV-8 infection on prostatic adenocarcinogenesis. A total number of one hundred formalin-fixed prostatic tissues were enrolled in this research; forty Prostate Adenocarcinoma (PAC) biopsies, forty biopsies from Benign Prostatic Hyperplasia (BPH), and twenty Apparently Normal Prostatic Tissues (ANPT) as a control group. Detection of HHV -8 DNA was achieved by a highly-sensitive variant of Chromogenic In Situ Hybridization (CISH) technique. In the mean age of PAC patients was 64.08±7.54years. Detection of CISH reactions for HHV 8- DNA was observed in tissues of 70% (28 out of 40) of PAC patients and 30% (12 out of 40) of BPH tissues, whereas no positive reactions were detected in the ANPT group. Detection of CISH reactions for HHV 8- DNA was observed in 55.6% of tissues of PAC patients with well grade histopathological examination, 87.5% of moderate grade, and 69.6% of poorly differentiated grade. It can be concluded that HHV-8 infection might contribute in prostate oncogenesis, together with other essential oncogenic viruses.

Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts.

ObjectiveThe aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing.MethodsWe performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompetent and immunocompromised hosts.ResultsOf the 926 patients tested for HHV-6 during the period of interest, 45 met the study criteria. Among immunocompetent hosts (n = 17), HHV-6 encephalitis was diagnosed to 4 infants or children presenting with seizures or mild encephalopathy during primary HHV-6 infection (CSF/blood replication ratio <<1 in all cases). Among immunocompromised hosts (n = 28), HHV-6 encephalitis was diagnosed to 7 adolescents/adults with hematologic conditions presenting with altered mental status (7/7), seizures (3/7), vigilance impairment (3/7), behavioral changes (2/7), hyponatremia (2/7), and anterograde amnesia (1/7). Initial brain MRI was altered only in 2 patients, but 6 of the 7 had a CSF/blood replication ratio >1.ConclusionsThe detection of a CSF/blood replication ratio >1 represented a specific feature of immunocompromised patients with HHV-6 encephalitis and could be of special help to establish a diagnosis of HHV-6 encephalitis in hematopoietic stem cell transplant recipients lacking radiologic evidence of limbic involvement.

Meningite causada por herpesvírus humano tipo 6: um relato de caso

Virus are a common cause of aseptic meningitis. In most cases (90%) the etiological agent is enterovirus, followed by arbovirus, HIV, adenovirus, influenza and the viruses of the Herpesviridae family. These include herpes simplex, which causes approximately 0.5% to 3% of aseptic meningitis, with herpes simplex 1 being the most frequent in this group. Human herpesvirus-6 (HHV-6), in rare cases, may also be associated with meningitis in combination with exanthema subitum. This report aims to present a rare case of meningoencephalitis caused by HHV-6 in an infant. In the present case, we have a male infant, 1 year and 2 months old, with a previous history of seizure and delayed neuropsychomotor development, referred to a tertiary hospital after a prompt evaluation with complaint of fever, irritability, somnolence and vomit-ing with 7 days of evolution. Analysis of cerebrospinal fluid with PCR positive for HHV-6. He was discharged in good general condition after 14 days of correct drug treatment. HHV-6 infection is often underdiagnosed because it has few specific symptoms. The etiologic identification is rec-ommended in children with atypical manifestations or immunodeficiency, allowing adequate treatment in an early manner, in order to avoid complications and mainly neurological sequelae.