Reactivation Of Herpesvirus Research Articles

Drug eruption with eosinophilia and systemic syndrome associated with reactivation of human herpesvirus 7, not human herpesvirus 6

The Journal of DermatologyVolume 39, Issue 7 p. 669-670 LETTERS TO THE EDITOR Drug eruption with eosinophilia and systemic syndrome associated with reactivation of human herpesvirus 7, not human herpesvirus 6 Hironori MORITO, Hironori MORITO Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorKana KITAMURA, Kana KITAMURA Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorTakaya FUKUMOTO, Takaya FUKUMOTO Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorNobuhiko KOBAYASHI, Nobuhiko KOBAYASHI Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorMasamitsu KUWAHARA, Masamitsu KUWAHARA Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorHideo ASADA, Hideo ASADA Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this author Hironori MORITO, Hironori MORITO Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorKana KITAMURA, Kana KITAMURA Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorTakaya FUKUMOTO, Takaya FUKUMOTO Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorNobuhiko KOBAYASHI, Nobuhiko KOBAYASHI Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorMasamitsu KUWAHARA, Masamitsu KUWAHARA Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this authorHideo ASADA, Hideo ASADA Department of Dermatology, Nara Medical University School of Medicine, Nara, JapanSearch for more papers by this author First published: 13 November 2011 https://doi.org/10.1111/j.1346-8138.2011.01365.xCitations: 8 Hironori Morito, M.D., Department of Dermatology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Email: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume39, Issue7July 2012Pages 669-670 RelatedInformation

Prospective monitoring of Epstein–Barr virus and other herpesviruses in patients with juvenile idiopathic arthritis treated with methotrexate and tocilizumab

Methotrexate (MTX) is widely used for the treatment of articular-type juvenile idiopathic arthritis (JIA), but patients receiving MTX for rheumatoid arthritis have been reported to be at increased risk of reactivation of Epstein-Barr virus (EBV) and the development of lymphoproliferative disorder. The association between MTX and reactivation of herpesviruses in pediatric patients is not yet understood. We prospectively monitored the viral load of EBV, cytomegalovirus (CMV), and herpesvirus 6 (HHV-6) in four JIA patients treated with MTX for 12-24months. Tocilizumab, an anti-interleukin 6 receptor monoclonal antibody, was added to the therapeutic regimen in three patients during the observation period. Prior to the administration of MTX, EBV and HHV-6 were detected by PCR in two patients. Significant increases in EBV and HHV-6 load were not observed following the administration of MTX or tocilizumab. In one patient, a relatively high EBV load remained detectable during 21months of observation in the absence of clinical symptoms. CMV was not detected throughout the observation period in any patient. This is the first report monitoring the longitudinal DNA loads of EBV and other herpesviruses in JIA patients. EBV and HHV-6 were often detectable, but treatment with MTX and tocilizumab did not appear to influence the viral load.

Fatigue and herpesvirus latency in women newly diagnosed with breast cancer

Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. The current study sought to determine biomarkers of fatigue that exist before cancer treatment. Relationships between the expression of latent Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and fatigue were examined in 158 women newly diagnosed with breast cancer or awaiting a positive diagnostic result. Higher CMV antibody titers, but not EBV antibody titers, were associated with a greater likelihood of being fatigued. Associations between fatigue and higher CMV antibody titers remained after controlling for alcohol use, smoking, comorbidities, depressive symptoms, age, BMI, cancer stage, and sleep problems. More sleep problems and higher levels of depressive symptoms were also associated with a greater likelihood of being fatigued. CMV antibody titers, but not EBV antibody titers, were associated with higher levels of C-reactive protein (CRP), but CRP was not associated with fatigue. When the cellular immune system is compromised, reactivation of latent herpesviruses may fuel chronic inflammatory responses. Prior work has suggested that fatigue may be related to inflammation and its associated sickness behaviors; accordingly, our findings may be tapping into this same physiological substrate.

Human herpesvirus 6: report of emerging pathogen in five patients with HIV/AIDS and review of the literature

The reactivation of human herpesvirus 6 (HHV-6) in patients with AIDS can result in an acute and severe diffuse meningoencephalitis. We describe the epidemiological, clinical and outcome findings of five patients with diagnosis of HIV/AIDS and central nervous system involvement (CNS) due to HHV-6. Fever was present in all the patients. Meningeal compromise, seizures and encephalitis were present in some of the patients. Polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) specimens was positive for HHV-6 in all the patients. HHV-6 should be included among opportunistic and emerging pathogens that involve the CNS in patients with AIDS.

Bilateral herpetic keratitis presenting with unilateral neurotrophic keratitis in pemphigus foliaceus: a case report.

IntroductionWe report a case of bilateral herpetic keratitis developing after rapid oral corticosteroid tapering in a patient with pemphigus foliaceus, which was followed by unilateral neurotrophic keratitis that was treated with amniotic membrane transplantation.Case presentationA 71-year-old Korean man developed bilateral herpetic keratitis one week after rapid tapering of systemic corticosteroid. He had been on high-dose oral corticosteroid and azathioprine therapy for six months for treatment of pemphigus foliaceus. Topical acyclovir ointment was prescribed. A week later, our patient's right eye had healed, but his left eye showed increased stromal edema with enlarged epithelial defects. He was prescribed oral acyclovir with topical broad-spectrum antibiotics applied to his left eye. The stromal edema cleared within a week but the epithelial defect remained unchanged. An amniotic membrane transplantation was performed on our patient's left eye, and his epithelial defect had totally healed three weeks later.ConclusionsPatients with autoimmune disease or who are on immunosuppressive therapy have a higher chance of developing bilateral herpetic keratitis. Although rare, the condition may be followed by unilateral neurotrophic keratitis. Rapid corticosteroid tapering may act as a triggering factor for viral infection or reactivation of herpes.

Herpes Zoster and Multiple Sclerosis

Multiple sclerosis (MS), a demyelinating disease of the central nervous system, has been considered multifactorial, and viruses may have a role in disease pathogenesis. Evidence suggests that certain viruses may trigger autoimmune neurological processes that lead to MS in genetically susceptible individuals [1, 2]. In this issue of the Journal, Kang et al analyze a database of 349,477 patients who had herpes zoster (experimental group) as a risk factor for MS (study outcome variable) in a region of the world historically considered low risk for MS. The authors compare their data with a randomly selected control group, more than 3 times as large as the initial sample (n 5 1,262,200), of participants who did not have herpes zoster. Their results show that the herpes zoster group had a 3.96 times greater risk of developing MS than did the control group (95% confidence interval [CI], 2.22–7.07, P % .001). This Kang et al study provides clear epidemiological observations suggesting a role for herpes zoster in the development of MS [3]. Previous studies noted that certain herpes viruses may trigger proinflammatory and autoimmune cascades through particles such as the toll-like receptor 4 (TLR-4) [3, 4], and that infectious environmental factors associated with MS may also belong to the herpesviridae family [4, 5]. This study highlights the time elapsed from the event of shingles until the occurrence of MS (approximately 100 d). In addition, evidence suggests that up to 30% of relapses among MS patients are associated with an infectious process [6, 7]. A possible explanation is the reactivation of latent herpes viruses by other infectious agents, and crossrecognition of common viral antigens with antigens found in the myelin sheath, which thereby induces molecular mimicry or superantigens [8–10]. The time lag for the occurrence of MS could be explained by a series of processes required by the immune systems of genetically susceptible individuals to reach a ‘‘threshold’’ and start the disease process. The threshold may also explain, in part, the observation that some patients have higher recurrence rates of MS around certain months of the year [11]. Some viruses of the herpesviridae family cause B cells to express alpha and beta crystal, a small stress protein that is normally absent from lymphoid tissues and has been considered an immunodominant antigen in the central nervous systems of MS patients [12]. Other studies have suggested a role of varicella zoster virus in the genesis of relapse and progression of some patients with chronic-progressive forms of MS [13, 14]. The evidence provided in this study by Kang et al allows us to better understand the role of these viral factors as an MS risk among certain genetically susceptible individuals. These epidemiological findings should be corroborated in other parts of the world to further clarify the role of varicella zoster virus and other herpes viruses in the pathogenesis of multiple sclerosis.

Evaluation of reactivation of HSV1, HHV6, CMV and EBV in a population of patients undergoing allogeneic bone marrow transplantation

Herpes viruses are recognized as important pathogens as a result of viral reactivation in immunocompromised hosts, especially in patients undergoing bone marrow transplantation. Objectives of this study were the assessment of the reactivation of herpes virus HSV1, HHV6, CMV and EBV and the correlation between viral reactivation and progression of transplantation in a population of patients undergoing allogeneic bone marrow transplantation at Fondazione IRCCS Ospedale Maggiore Ca’ Granda Policlinico, Milan. Viral DNA was detected and quantified by Real Time PCR in a population of 35 patients undergoing allogeneic bone marrow transplantation. The viral reactivation was observed in 7 patients for HSV1 (20%), 6 patients for HHV6 (17.1%), 11 patients for CMV (31.4%) and 4 patients for EBV (11.4%). Difference in the incidence of aGVDH between patients with viral reactivation versus those for which there was no reactivation was statistically significant. These data confirm the importance of monitoring viral load for the management of antiviral therapy in order to prevent CMV disease and complications related to herpes viruses reactivation.

Control of Kaposi's Sarcoma-Associated Herpesvirus Reactivation Induced by Multiple Signals

The ability to control cellular functions can bring about many developments in basic biological research and its applications. The presence of multiple signals, internal as well as externally imposed, introduces several challenges for controlling cellular functions. Additionally the lack of clear understanding of the cellular signaling network limits our ability to infer the responses to a number of signals. This work investigates the control of Kaposi's sarcoma-associated herpesvirus reactivation upon treatment with a combination of multiple signals. We utilize mathematical model-based as well as experiment-based approaches to achieve the desired goals of maximizing virus reactivation. The results show that appropriately selected control signals can induce virus lytic gene expression about ten folds higher than a single drug; these results were validated by comparing the results of the two approaches, and experimentally using multiple assays. Additionally, we have quantitatively analyzed potential interactions between the used combinations of drugs. Some of these interactions were consistent with existing literature, and new interactions emerged and warrant further studies. The work presents a general method that can be used to quantitatively and systematically study multi-signal induced responses. It enables optimization of combinations to achieve desired responses. It also allows identifying critical nodes mediating the multi-signal induced responses. The concept and the approach used in this work will be directly applicable to other diseases such as AIDS and cancer.

Neuraxial Morphine and Oral Herpes Reactivation in the Obstetric Population

Survey of Anesthesiology: June 2011 - Volume 55 - Issue 3 - p 134-136 doi: 10.1097/01.SA.0000396289.06471.17

Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein–Barr positive epithelial cells

Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein–Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.

Reactive Oxygen Species Hydrogen Peroxide Mediates Kaposi's Sarcoma-Associated Herpesvirus Reactivation from Latency

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the host following an acute infection. Reactivation from latency contributes to the development of KSHV-induced malignancies, which include Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients, primary effusion lymphoma and multicentric Castleman's disease. However, the physiological cues that trigger KSHV reactivation remain unclear. Here, we show that the reactive oxygen species (ROS) hydrogen peroxide (H2O2) induces KSHV reactivation from latency through both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic replication, and KSHV reactivation from latency induced by oxidative stress, hypoxia, and proinflammatory and proangiogenic cytokines are mediated by H2O2. Mechanistically, H2O2 induction of KSHV reactivation depends on the activation of mitogen-activated protein kinase ERK1/2, JNK, and p38 pathways. Significantly, H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase and glutathione inhibit KSHV lytic replication in culture. In a mouse model of KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and significantly prolongs the lifespan of the mice. These results directly relate KSHV reactivation to oxidative stress and inflammation, which are physiological hallmarks of KS patients. The discovery of this novel mechanism of KSHV reactivation indicates that antioxidants and anti-inflammation drugs could be promising preventive and therapeutic agents for effectively targeting KSHV replication and KSHV-related malignancies.

Le DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)

Drug-induced hypersensitivity syndrome or DRESS is an uncommon but potentially severe cutaneous adverse drug reaction. This cutaneous drug adverse reaction has some particular characteristics: a small number of culprit drugs, long delay (three to six weeks) for development after the first drug intake, responsibility of some viruses, especially Human Herpesvirus 6 (HHV6). The awareness of this cutaneous adverse reaction has increased during the last years with a better knowledge including the relationship between some drugs and reactivation of Herpesviruses, antiviral immune response, and genetic background. The identification of DRESS is important for rheumatologist who is often using drugs at risk for DRESS (allopurinol, salazopyrine, antiépileptiques…). This recognition enables a rapid diagnosis and a proper management of this syndrome.

Herpes viruses and tumours in kidney transplant recipients. The role of immunosuppression

Herpes virus infections are frequent in renal transplant recipients. Some herpes viruses are not only responsible for life-threatening infections and renal graft injury but can also increase the risk of malignancy. Three herpes viruses, namely cytomegalovirus (CMV) or human herpes virus 5, Epstein-Barr virus (EBV) or herpes virus 4 and human herpes virus 8 (HHV8), may play an oncogenic role. The oncogenic role of CMV is controversial. However, there is growing evidence showing that CMV can infect cancer cells and favour their resistance to the immune system and chemotherapy. B cells infected by EBV can have uncontrolled proliferation eventually resulting in polyclonal polymorphic or monomorphic post-transplant lymphoproliferative diseases (PTLD), which are particularly frequent in children and in EBV-negative recipients. In some ethnicities, the carriers of HHV8 are susceptible to develop Kaposi's sarcoma after transplantation. The intensity of immunosuppression therapy plays a critical role in mediating infections from oncogenic herpes viruses. However, the type of immunosuppressive drugs can also influence the risk of virus-mediated neoplasias. An aggressive induction therapy aimed at depleting lymphocytes may favour the reactivation and dissemination of oncogenic herpes viruses, while anti-CD25 monoclonal antibodies have little impact on virus reactivation. Calcineurin inhibitors can increase the risk of viral infections and malignancy. Mycofenolate salts may perhaps protect from EBV-related PTLD. Finally, the inhibitors of the mammalian target of rapamycine may reduce the risk of viral disease by inhibiting the cascade of kinases that govern the proliferation and replication of oncogenic herpes viruses.

Thyroïdite auto-immune et syndrome d’hypersensibilité médicamenteuse (DRESS) associés à une réactivation virale HHV6

DRESS syndrome is a severe adverse drug reaction with visceral involvement. Its physiopathology includes immunological disorders associated with human herpes virus (HHV) reactivation. We report two cases of auto-immune thyroiditis occurring in the context of DRESS syndrome associated with HHV-6 reactivation. Case 1 : A 39-year-old woman presented DRESS syndrome with HHV-6 reactivation, cutaneous, lymph node, hepatic and renal disorders treated with systemic corticosteroids for 10 months. Following discontinuation of the corticosteroids, she developed Graves's disease, which was stabilized with carbimazole and a beta-blocker. CASE 2: A 31-year-old woman was hospitalized for DRESS syndrome with delayed HHV-6 reactivation and severe hepatic involvement. She was successfully treated by topical steroids. Six weeks later, she presented De Quervain thyroiditis associated with moderate relapsing DRESS, which were treated by sodium levothyroxine and topical steroids. There is currently debate about the implication of viral reactivation, in particular HHV-6, in chronic DRESS, relapse and development of auto-immune diseases. These observations highlight the potential risk of patients developing auto-immune diseases and underline the need for prolonged clinical and laboratory follow-up of patients with DRESS.

Role of the cellular transcription factor YY1 in the latent-lytic switch of Kaposi's sarcoma-associated herpesvirus

Lytic cycle reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) is initiated by expression of the ORF50 gene. Here we show that YY1 protein specifically binds to the ORF50 promoter (ORF50p) region in vitro and in vivo. After treatment with chemical inducers, including sodium butyrate (SB) and TPA, the levels of YY1 protein are inversely correlated with the lytic induction of KSHV in cells. Overexpression of YY1 completely blocks the ORF50p activation in transient reporter assays, while mutation at the YY1 site in the ORF50p or knockdown of YY1 protein confers an enhancement of the ORF50p activation induced by SB and TPA. YY1 overexpression in a stable cell clone HH-B2(Dox-YY1) also inhibits expression of the ORF50 and its downstream lytic genes. On the other hand, a chimeric YY1 construct that links to its coactivator E1A can disrupt viral latency. These results imply that YY1 is involved in the regulation of KSHV reactivation.

Unsuitability of exhaled breath condensate for the detection of Herpesviruses DNA in the respiratory tract

Exhaled breath condensate is a non-invasive method for detecting a wide number of molecules as well as genomic DNA in the airways. No study investigated the detection of viral DNA in exhaled breath condensate, while only one study excluded its usefulness for detection of influenza virus RNA. In this study, the suitability of exhaled breath condensate for detecting herpesviruses infection or reactivation in the respiratory tract of lung transplant recipients was evaluated.Twenty-four matched samples (exhaled breath condensate, bronchoalveolar lavage, whole blood, transbronchial biopsy) were evaluated for the detection of human cytomegalovirus (HCMV), human herpesvirus (HHV-6 and -7), Epstein-Barr virus (EBV) DNA by real-time PCR.Eighteen bronchoalveolar lavages (75%), six whole blood samples (25%), and two transbronchial biopsies (8.3%) were positive for at least one herpesvirus. Only one exhaled breath condensate specimen was positive for HCMV DNA (and positive also in the bronchoalveolar lavage, with low viral load in both specimens); while no other patient, irrespective of the viral load in any specimen or the presence of clinical symptoms and signs, had a positive exhaled breath condensate.These findings seem to exclude the suitability of exhaled breath condensate for non-invasive detection of viral DNA in the respiratory tract of lung transplant recipients.

Case of drug rash with eosinophilia and systemic symptoms induced by zonisamide and reactivation of human herpes virus 7

Case of drug rash with eosinophilia and systemic symptoms induced by zonisamide and reactivation of human herpes virus 7

Herpes simplex virus reactivation as a complication of photodynamic therapy

We report the case of an 81-year-old male patient who developed a reactivation of herpes simplex virus localized to the right forehead, where photodynamic therapy (PDT) for actinic keratosis was performed. Considering the wide use of PDT, herpes virus infection or reactivation as well as other infections seem to be a very rare but potentially serious complication that has to be distinguished from common inflammatory reactions after PDT. Further applications of PDT under antiviral prophylaxis were well tolerated by our patient, with no further herpetic reactivation and successful treatment of actinic keratoses.

Fatigue in Medical Residents Leads to Reactivation of Herpes Virus Latency

The main objective of this study was to detect fatigue-induced clinical symptoms of immune suppression in medical residents. Samples were collected from the subjects at rest, following the first night (low-stress), and the last night (high-stress) of night float. Computerized reaction tests, Epworth Sleepiness Scale, and Wellness Profile questionnaires were used to quantify fatigue level. DNA of human herpes viruses HSV-1, VZV, EBV, as well as cortisol and melatonin concentrations, were measured in saliva. Residents at the high-stress interval reported being sleepier compared to the rest interval. EBV DNA level increased significantly at both stress intervals, while VZV DNA level increased only at low-stress. DNA levels of HSV-1 decreased at low-stress but increased at high-stress. Combined assessment of the viral DNA showed significant effect of stress on herpes virus reactivation at both stress intervals. Cortisol concentrations at both stress intervals were significantly higher than those at rest.

Complications of Corneal Collagen Cross-Linking

Cross-linking of corneal collagen (CXL) is a promising approach for the treatment of keratoconus and secondary ectasia. Several long-term and short-term complications of CXL have been studied and documented. The possibility of a secondary infection after the procedure exists because the patient is subjected to epithelial debridement and the application of a soft contact lens. Formation of temporary corneal haze, permanent scars, endothelial damage, treatment failure, sterile infiltrates, and herpes reactivation are the other reported complications of this procedure. Cross-linking is a low-invasive procedure with low complication and failure rate but it may have direct or primary complications due to incorrect technique application or incorrect patient's inclusion and indirect or secondary complications related to therapeutic soft contact lens, patient's poor hygiene, and undiagnosed concomitant ocular surface diseases.