Acute Herpesvirus Infection Research Articles

Association analysis between symptomology and herpesvirus IgG antibody concentrations in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS) are two complex and multifactorial diseases whose patients experience persistent fatigue, cognitive impairment, among other shared symptoms. The onset of these diseases has also been linked to acute herpesvirus infections or their reactivations. In this work, we re-analyzed a previously-described dataset related to IgG antibody responses to 6 herpesviruses (CMV – cytomegalovirus; EBV – Epstein-Barr virus; HHV6 – human herpesvirus-6; HSV1 and HSV2 – herpes simplex virus-1 and -2, respectively; VZV – varicella-zoster virus) from the United Kingdom ME/CFS biobank. The primary goal was to report the underlying symptomology and its association with herpesvirus IgG antibodies using data from 4 disease-trigger-based subgroups of ME/CFS patients (n = 222) and patients with MS (n = 46). The secondary objective was to assess whether serological data could distinguish ME/CFS and its subgroup from MS using a SuperLearner (SL) algorithm. There was evidence for a significant negative association between temporary eye insight disturbance and CMV antibody concentrations and for a significant positive association between bladder problems and EBV antibody concentrations in the MS group. In the ME/CFS or its subgroups, the most significant antibody-symptom association was obtained for increasing HSV1 antibody concentration and brain fog, a finding in line with a negative impact of HSV1 exposure on cognitive outcomes in both healthy and disease conditions. There was also evidence for a higher number of significant antibody-symptom associations in the MS group than in the ME/CFS group. When we combined all the serological data in an SL algorithm, we could distinguish three ME/CFS subgroups (unknown disease trigger, non-infection trigger, and an infection disease trigger confirmed in the lab at the time of the event) from the MS group. However, we could not find the same for the remaining ME/CFS group (related to an unconfirmed infection disease). In conclusion, IgG antibody data explains more the symptomology of MS patients than the one of ME/CFS patients. Given the fluctuating nature of symptoms in ME/CFS patients, the clinical implication of these findings remains to be determined with a longitudinal study. This study is likely to ascertain the robustness of the associations during natural disease course.

Melatonin as an immunomodulator in combined therapy of herpesvirus skin diseases associated with HIV

Introduction. Highly active antiretroviral therapy is the current standard of care for patients with HIV/AIDS. Although antiretroviral therapy is etiotropic, quite effective in reducing viral load, recurrent opportunistic infections can lead to adverse effects in the management of such patients, and side effects may limit its effectiveness. Among opportunistic infections, a large group are herpesvirus infections, they are frequent manifestations of dermatological manifestations of HIV, which can sometimes lead to death. Melatonin (N-acetyl-5-methoxytryptamine) was thought to be of purely epiphyseal origin, but recent studies have shown that melatonin synthesis can occur in some other cells and organs of the human body. In addition, it was found that melatonin regulates circadian rhythms, has a number of important functions and areas of influence. Studying its structure and action, researches over the past decade have shown that melatonin enhances the immune response of T-helpers, stimulates the production of cytokines, has antioxidant properties. Due to these effects, and possibly other mechanisms yet to be determined, melatonin has been shown to reduce drug toxicity and have immunomodulatory effects. Objective: to study the effectiveness of melatonin as an immunomodulatory agent in herpesvirus skin diseases associated with HIV as part of combined therapy. Objectives of the study: to determine serum levels of CD4 + cells and to investigate changes in immunogram parameters in patients with herpesvirus infection associated with HIV before and after melatonin therapy and to compare them with the levels of the control group. Materials and methods. In the current study, HIV patients who had an acute herpesvirus infection caused by HSV-1, HSV-2, VZV, EBV, and HHV-8 were selected. Patients were divided into two groups: group I consisted of patients receiving antiretroviral therapy, valaciclovir in standard therapeutic doses and melatonin as immunomodulatory therapy, once daily, in the evening at a dose of 3 mg. Group II included patients who received antiretroviral therapy alone in combination with valaciclovir. Clinical and laboratory evaluation was performed before and after 30 days of therapeutic intervention. Patients were asked to report any complications. Results. The study involved forty HIV patients who had an exacerbation of herpesvirus infection; the levels of CD4 + cells averaged 311 ± 128. All patients received antiretroviral therapy for at least five years with a mean infection period of 10 years. The age of patients ranged from 32 to 60 years with a mean of 41.4 ± 17.2 years. After treatment, CD4 + cells were significantly higher in group I subjects receiving antiretroviral therapy in combination with valaciclovir and melatonin than in control subjects wo not receiving melatonin after one month of treatment. The level of CD4 + cells was 37 % higher in patients taking melatonin compared with the control group (p < 0.05). The current study showed that 60% of patients (12/20) had positive changes in the parameters of the immunogram (p < 0.05). Significant differences between groups, which were statistically validity in levels of CD4 + cells and immunogram parameters, indicate that melatonin had a positive effect on the state of the immune system. Conclusion. Our study has proven the beneficial effect of melatonin on the state of the immune system in patients herpesvirus skin diseases associated with HIV. Given the low toxicity of melatonin and its ability to reduce side effects and increase the effectiveness of therapeutic agents, its use may be important and significant in combination therapy in combination with highly active antiretroviral therapy.

Клинико-патогенетические проявления у кошек при инфекционном ринотрахеите

Feline herpesvirus is widespread and initiates respiratory infections in representatives of the feline family, including in Moscow. The article shows that acute herpesvirus infection in cats occurs with upper respiratory tract syndrome, conjunctivitis, and fever. Sick cats of various breeds and contents were identified, but more often they get sick at the age of 2 months to a year. The virus is transmitted aerogenically and with secretions from the nose, mouth, eyes when sick animals come into contact with healthy ones. Various stress factors, colds, cause the reactivation of the virus also with release into the environment. Therefore, the disease is more often recorded in the cold season (homeless animals) and during the rainy season it lasts 7–10 days but a relapse or transition to a chronic form is possible. With the group keeping of cats (shelter), the disease can significantly spread and acquire the character of an epizootic. PCR is an objective assessment criterion for virus detection and differential diagnosis.

Seroprevalence to herpesviruses in patients with primary brain gliomas

Purpose of the study . The purpose of the study was to assess the level of seroprevalence and the frequency of detection of serological markers of acute herpesvirus infection in patients with PGBT in comparison with those in patients with chronic non-tumor diseases. Materials and methods . Before conducting antitumor therapy, the blood serum of 42 patients with PGBT (the main group) was studied. The comparison group consisted of 137 patients with chronic non-tumor diseases. Antibodies of classes M and G to herpes simplex virus types 1, 2 (HSV-1,2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus type 6 (HHV-6) were determined by ELISA using JSC Vector-Best reagent kits. Results . Among patients with PGBT, seropositive for HSV-1,2 were 95.2%, CMV — 92.9%, EBV — 100%, HHV-6-40.5% of patients. No statistically significant differences in seroprevalence and the presence of markers of acute infection (IgM) were found either in comparison with non-tumor diseases or depending on the malignancy grade. Antibodies to HSV-1,2, CMV and EBV in patients with gliomas were significantly more often found in the medium range, and in the comparison group — in the high values of coefficient of positivity (CP) for IgG. In all the studied groups, antibodies to HHV-6 were determined statistically significantly less frequently than to other herpes viruses. Conclusion . The absence of statistically significant differences in seropositivity between groups of patients and their presence between pathogens is most likely a reflection of general trends in the population, and the question of the involvement of various representatives of the Herpesviridae family in neuro-oncogenesis of primary glial brain tumors still remains open.

Different effects of the immunostimulatory drug Stimforte on infections of hepatitis C virus and herpes simplex virus type 1.

Stimforte, an immune response-stimulating preparation, is active with respect to hepatitis C virus (HCV) and herpes simplex virus type I (HSV-1). The effects of Stimforte in animals infected with either HCV or HSV-1 are fundamentally different. In mice with acute herpes virus infection, Stimforte administration leads to a higher activity of natural killer cells and cytotoxic lymphocytes, and the amount of interferon (IFN) λ grows. In mice infected with HCV, Stimforte administration results in a significant increase in IFN-β but not IFN-λ in blood and affected organs. Stimforte has been found to affect directly HCV reproduction that causes the infected cell death, but it does not affect HSV-1 reproduction in the Vero cells (V).

Universal Trichloroacetic Acid Peel Technique for Light and Dark Skin.

Despite their great potential, medium and deep trichloroacetic acid peels are underused in light-skinned patients and are rarely used in darker-skinned patients because of the widespread fear of pigmentary complications and scarring. This concern has led many physicians to opt for the use of lighter types of peels (glycolic acid peel, Jessner peel, etc) and different lasers and intense light technologies. Trichloroacetic acid peels have been described in numerous publications. However, no study to date has described the precise technique and the practical pearls of a successful trichloroacetic acid peel approach in a clear, detailed, and reproducible manner. To clarify a practical approach to a universal trichloroacetic acid peel and to offer novice and experienced facial plastic surgeons an organized, easy, and safe technique for medium and deep trichloroacetic acid peels. This study was a case series of universal trichloroacetic acid peels in an academic setting. The study dates were January 1, 1996, to November 1, 2015. This article discusses the preoperative evaluation for a chemical peel, a previously published genetico-racial skin classification, and the trichloroacetic acid peel technique, which aims at standardizing and controlling the application of the acid to improve results and lessen complications. The "strip" technique is described, which increases the physician's control over the peel depth. A total of 923 trichloroacetic acid peels in 803 female patients (87.0%) and 120 male patients (13.0%) were reviewed (mean age, 41.59 years). The follow-up period ranged from 6 months to 13 years (mean, 13 months). This case series revealed a low incidence of complications, including 54 patients (5.9%) with persistent hyperpigmentation, 3 patients (0.3%) with mild telangiectasia, 2 patients (0.2%) with acute herpesvirus infection, 2 patients (0.2%) with bacterial Staphylococcus infection, and 1 patient (0.1%) with hypopigmentation. When properly applied, trichloroacetic acid peels are efficient and safe for light and dark skin. The technique can be an easily implementable addition to a physician's cosmetic practice. 4.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Herpesvirus Infections and Childhood Arterial Ischemic Stroke: Results of the VIPS Study.

Epidemiological studies demonstrate that childhood infections, including varicella zoster virus, are associated with an increased risk of arterial ischemic stroke (AIS). Other herpesviruses have been linked to childhood AIS in case reports. We sought to determine whether herpesvirus infections, which are potentially treatable, increase the risk of childhood AIS. We enrolled 326 centrally confirmed cases of AIS and 115 stroke-free controls with trauma (29 days to 18 years of age) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7-28 days later) when feasible. Samples were tested by commercial enzyme-linked immunosorbent assay kits for immunoglobulin M/immunoglobulin G antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus. An algorithm developed a priori classified serological evidence of past and acute herpesvirus infection as dichotomous variables. The median (quartiles) age was 7.7 (3.1-14.3) years for cases and 10.7 (6.9-13.2) years for controls (P=0.03). Serological evidence of past infection did not differ between cases and controls. However, serological evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socioeconomic status (odds ratio, 2.2; 95% confidence interval, 1.2-4.0; P=0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection; herpes simplex virus 1 was found most often. Most infections were asymptomatic. Herpesviruses may act as a trigger for childhood AIS, even if the infection is subclinical. Antivirals like acyclovir might have a role in the prevention of recurrent stroke if further studies confirm a causal relationship.

IL-22 driven neutrophils afford critical protection from acute murine cytomegalovirus infection (P6310)

Abstract Pathogenic herpesviruses including cytomegalovirus target numerous host organs during infection, but the immunological mechanisms that afford antiviral protection in different tissue microenvironments require a better understanding. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that neutrophils are critical antiviral effector cells that counter acute herpesvirus infection. Depletion of Ly6G+ neutrophils exacerbated virus-induced weight loss and elevated virus load in a tissue-restricted manner. Neutrophils profoundly and directly inhibited virus replication in vitro. MCMV-elicited neutrophil responses were orchestrated by interleukin-22 (IL-22), which was expressed by conventional NK cells and induced neutrophil-attractant chemokines in MCMV-infected peripheral organs. These data demonstrate that IL-22 affords anti-herpesvirus infection in peripheral tissue and highlights a previously unappreciated and critical role for neutrophils in countering cytomegalovirus infection.

Naturally transmitted herpesvirus papio-2 infection in a black and white colobus monkey

A 6.5-year-old female eastern black and white colobus monkey (Colobus guereza) was evaluated after acute onset of ataxia and inappetence. The monkey was ataxic and lethargic, but no other abnormalities were detected via physical examination, radiography, or clinicopathologic analyses. During the next 2 days, the monkey's clinical condition deteriorated, and its WBC count decreased dramatically. Cytologic examination of a CSF sample revealed marked lymphohistiocytic inflammation. Despite supportive care, the monkey became apneic; after 20 hours of mechanical ventilation, fatal cardiac arrest occurred. At necropsy, numerous petechiae were detected within the white matter tracts of the brain; microscopic lesions of multifocal necrosis and hemorrhage with intranuclear inclusions identified in the brain and adrenal glands were consistent with an acute herpesvirus infection. A specific diagnosis of herpesvirus papio-2 (HVP-2) infection was made on the basis of results of serologic testing; PCR assay of tissue specimens; live virus isolation from the lungs; and immunohistochemical identification of the virus within brain, spinal cord, and adrenal gland lesions. Via phylogenetic tree analysis, the colobus HVP-2 isolate was grouped with neuroinvasive strains of the virus. The virus was most likely transmitted to the colobus monkey through toys shared with a nearby colony of baboons (the natural host of HVP-2). To the authors' knowledge, this is the first reported case of natural transmission of HVP-2 to a nonhost species. Infection with HVP-2 should be a differential diagnosis for acute encephalopathy in primate monkeys and humans, particularly following exposure to baboons.

Herpes simplex virus interferes with amyloid precursor protein processing.

BackgroundThe early events underlying Alzheimer's disease (AD) remain uncertain, although environmental factors may be involved. Work in this laboratory has shown that the combination of herpes simplex virus type 1 (HSV1) in brain and carriage of the APOE-ε4 allele of the APOE gene strongly increases the risk of developing AD. The development of AD is thought to involve abnormal aggregation or deposition of a 39–43 amino acid protein – β amyloid (Aβ) – within the brain. This is cleaved from the much larger transmembranal protein 'amyloid precursor protein' (APP). Any agent able to interfere directly with Aβ or APP metabolism may therefore have the capacity to contribute towards AD. One recent report showed that certain HSV1 glycoprotein peptides may aggregate like Aβ; a second study described a role for APP in transport of virus in squid axons. However to date the effects of acute herpesvirus infection on metabolism of APP in human neuronal-type cells have not been investigated. In order to find if HSV1 directly affects APP and its degradation, we have examined this protein from human neuroblastoma cells (normal and transfected with APP 695) infected with the virus, using Western blotting.ResultsWe have found that acute HSV1 (and also HSV2) infection rapidly reduces full length APP levels – as might be expected – yet surprisingly markedly increases levels of a novel C-terminal fragment of APP of about 55 kDa. This band was not increased in cells treated with the protein synthesis inhibitor cycloheximideConclusionHerpes virus infection leads to rapid loss of full length APP from cells, yet also causes increased levels of a novel 55 kDa C-terminal APP fragment. These data suggest that infection can directly alter the processing of a transmembranal protein intimately linked to the aetiology of AD.

Herpes simplex virus helicase-primase inhibitors are active in animal models of human disease.

Herpes simplex virus infections are the cause of significant morbidity, and currently used therapeutics are largely based on modified nucleoside analogs that inhibit viral DNA polymerase function. To target this disease in a new way, we have identified and optimized selective thiazolylphenyl-containing inhibitors of the herpes simplex virus (HSV) helicase-primase enzyme. The most potent compounds inhibited the helicase, the primase and the DNA-dependent ATPase activities of the enzyme with IC50 (50% inhibitory concentration) values less than 100 nM. Inhibition of the enzymatic activities was through stabilization of the interaction between the helicase-primase and DNA substrates, preventing the progression through helicase or primase catalytic cycles. Helicase-primase inhibitors also prevented viral replication as demonstrated in viral growth assays. One compound, BILS 179 BS, displayed an EC50 (effective concentration inhibiting viral growth by 50%) of 27 nM against viral growth with a selectivity index greater than 2,000. Antiviral activity was also demonstrated for multiple strains of HSV, including strains resistant to nucleoside-based therapies. Most importantly, BILS 179 BS was orally active against HSV infections in murine models of HSV-1 and HSV-2 disease and more effective than acyclovir when the treatment frequency per day was reduced or when initiation of treatment was delayed up to 65 hours after infection. These studies validate the use of helicase-primase inhibitors for the treatment of acute herpesvirus infections and provide new lead compounds for optimization and design of superior anti-HSV agents.

Recommended procedures for the diagnosis of persistent active herpesvirus infections

While reliable tests are available to diagnose acute herpesvirus infections, this does not apply equally well to the identification of chronic active or recurrent infections. Common serology in most cases is not very reliable, unless the antibody response is carefully dissected to determine the response to some early antigens related to viral replication, such as against EA complex in Epstein-Barr virus infections. There are a number of techniques that hold some promise for the future: antigen demonstration by monoclonal antibodies such as in the shell vial assay or in tissue culture cells exposed to body fluids; in situ hybridization for viral DNA and polymerase chain reaction; and antigen assays by combined blotting/monoclonal antibody techniques. In developing meaningful parameters for defining persistent active or reactivated herpesvirus infections, techniques for quantitating virus and/or antigen should be helpful.