Reactivation Of Dormant Virus Research Articles

Reactivation of herpesvirus type 6 and IgA/IgM-mediated responses to activin-A underpin long COVID, including affective symptoms and chronic fatigue syndrome.

Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID. To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5′-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709). Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.

Vaccine Induced Herpes Zoster in An Immunocompetent Child After 3 months of 1st Dose of Vaccination

Varicella zoster virus (VZV) is an enveloped double stranded linear virus, which belongs to the herpesvirus’s family. It can cause two clinically different forms of diseases, primary infection known as chicken pox and latent infection know as herpes zoster (Shingles). Primary infection presents with diffuse vesicular rash accompanied by fever, malaise, and pharyngitis. However, latent infection results from reactivation of dormant virus in an immunocompromised patient and presents with painful localized skin rashes called as shingles. Currently, in the US, 2 doses of live attenuated varicella vaccine are available to prevent VZV infection. One of the major side effects of vaccination are the rashes. We report a unique case of vaccine induced VZV infection in a previously healthy child that presents with vesicular rashes 3 months after 1st dose of vaccination. A 16-month-old child with past medical history of premature birth at 32 weeks, presented to the pediatric outpatient clinic with complains of well-demarcated, erythematous, dry rash on both labia. Parents denied fever, cough, or any other signs and symptoms associated with rashes. patient activity level was normal and oral intake was usual. PCR testing was performed was found to be negative for Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2) and positive for VZV. Due to patient recent vaccination status, further classification of infection was needed to determine if the source of infection was wild type chicken pox or vaccine induced. A swab of one of the vesicular lesions was sent to the Ohio Department of Health, for vaccine vs wild-type strain PCR testing. The results were positive for Vaccine induced VZV infection. The patient was started on acyclovir therapy. On follow-up, the patient condition improved clinically. In pediatric populations, it is important to do extensive evaluation of rashes post vaccination as it can be occurred due to wild type, break through or it can be vaccine induced virus. Proper evaluation can significantly impact the management patients as they are maybe infectious and need to be isolated in wild type and breakthrough infection versus non-infectious in case of vaccine induced. After detailed clinical history and physical examination, it is important to investigate further through PCR testing to differentiate one category from another!

Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4 + T Lymphocytes Isolated from HIV-1-Infected Individuals Receiving Suppressive Combined Antiretroviral Therapy

The presence of latently infected cells remains a key obstacle to the development of a functional HIV-1 cure. Reactivation of dormant viruses is possible with latency-reversing agents, but the effectiveness of these compounds and the subsequent immune response require optimization if the eradication of HIV-1-infected cells is to be achieved. Here, we describe the use of a chimeric antigen receptor, comprised of T cell activation domains and a broadly neutralizing antibody, VRC01, targeting HIV-1 to treat the infected cells. T cells expressing this construct exerted specific cytotoxic activity against wild-type HIV-1-infected cells, resulting in a dramatic reduction in viral rebound in vitro, and showed persistent effectiveness against reactivated latently infected T lymphocytes from HIV-1 patients receiving combined antiretroviral therapy. The methods used in this study constitute an improvement over existing CD4-based CAR-T technology and offer a promising approach to HIV-1 immunotherapy.

Sepsis-induced immune alterations monitoring by flow cytometry as a promising tool for individualized therapy.

Septic syndromes remain a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units. While sepsis has, for long, been solely described as inducing a tremendous systemic inflammatory response, novel findings indicate that sepsis indeed initiates a more complex immunologic response that varies over time, with the concomitant occurrence of both pro- and anti-inflammatory mechanisms. As a resultant, after a short proinflammatory phase, septic patients enter a stage of protracted immunosuppression. This is illustrated in those patients by reactivation of dormant viruses (CMV or HSV) or infections due to pathogens, including fungi, which are normally pathogenic solely in immunocompromised hosts. Although mechanisms are not totally understood, these alterations might be directly responsible for worsening outcome in patients who survived initial resuscitation as nearly all immune functions are deeply compromised. Indeed, the magnitude and persistence over time of these dysfunctions have been associated with increased mortality and health-care associated infection rate. Consequently, new promising therapeutic avenues are currently emerging from those recent findings such as adjunctive immunostimulation (IFN-γ, GM-CSF, IL-7, anti-PD1/L1 antibodies) for the most immunosuppressed patients. Nevertheless, as there is no clinical sign of immune dysfunctions, the prerequisite for such therapeutic intervention relies on our capacity in identifying the patients who could benefit from immunostimulation. To date, the most robust biomarkers of sepsis-induced immunosuppression are measured by flow cytometry. Of them, the decreased expression of monocyte HLA-DR appears as a "gold standard." This review reports on the mechanisms sustaining sepsis-induced immunosuppression and its related biomarkers measurable by flow cytometry. The objective is to integrate the most recent facts in an up-to-date account of clinical results, flow cytometry aspects as well as issues in results standardization for multicenter studies. © 2015 International Clinical Cytometry Society.

Delayed Facial Paralysis following Uneventful KTP Laser Stapedotomy: Two Case Reports and a Review of the Literature.

Facial palsy that occurs immediately after middle ear surgery (stapedectomy, stapedotomy, and tympanoplasty) can be a consequence of the local anesthetics and it regresses completely within a few hours. In the case of delayed facial palsy, the alarming symptom occurs several days or even weeks after uneventful surgery. The mechanism of the neural dysfunction is not readily defined. Surgical stress, intraoperative trauma, or laceration of the chorda tympani nerve with a resultant retrograde facial nerve edema can all be provoking etiological factors. A dehiscent bony facial canal or a multiple microporotic fallopian canal (microtrauma or laser effect) can also contribute to the development of this rare phenomenon. The most popular theory related to the explanation of delayed facial palsy at present is the reactivation of dormant viruses. Both the thermal effect of the laser and the elevation of the tympanomeatal flap can reactivate viruses resting inside the ganglion geniculi, facial nerve, or facial nuclei. The authors report the case histories of a 55-year-old female, and a 45-year-old male who presented with a delayed facial palsy following laser stapedotomy. The clinical characteristics, the therapeutic options, and the possibility of prevention are discussed.

ICU-acquired immunosuppression and the risk for secondary fungal infections

Sepsis and related infectious syndromes, including nosocomial infections, represent a major but largely under recognized healthcare problem worldwide, accounting for thousands of deaths every year. After a short pro-inflammatory phase, severely injured ICU patients enter a stage of protracted immunosuppression illustrated by reactivation of dormant viruses or infections due to microorganisms, including fungi, which are normally pathogenic solely in immunocompromised hosts. This brief review will focus on immune dysfunctions described so far in ICU patients regarding monocytes and T lymphocytes (as examples for innate and adaptive immune cells) and on their potential use as biomarkers for identification of patients at risk of secondary nosocomial infections and for guidance of immunotherapy. Finally, we will more specifically focus on the risk for fungal infections in ICU patients, and on the potential beneficial effects of adjunctive therapy not only to prevent these infections, but also to reinforce immune responses once they are already diagnosed.

Recommandation de bonne pratiqueB: Les stratégies thérapeutiques médicamenteuses et non médicamenteuses de l'aide à l'arrêt du tabac

Introduction of cART in 1996 has drastically increased the life expectancy of people living with HIV-1. However, this treatment has not allowed cure as cessation of cART is associated with a rapid viral rebound. The main barrier to the eradication of the virus is related to the persistence of latent HIV reservoirs. Evidence is now accumulating that purging the HIV-1 reservoir might lead to a cure or a remission. The most studied strategy is the so called “shock and kill” therapy. This strategy is based on reactivation of dormant viruses from the latently-infected reservoirs (the shock) followed by the eradication of the reservoirs (the kill). This review focuses mainly on the recent advances made in the “shock and kill” therapy. We believe that a cure or a remission will come from combinatorial approaches i.e. combination of drugs to reactivate the dormant virus from all the reservoirs including the one located in sanctuaries, and combination of strategies boosting the immune system. Alternative strategies based on cell and gene therapy or based in inducing deep latency, which are evoked in this review reinforce the idea that at least a remission is attainable.