scholarly journals In vitrotoxicity and efficacy of verdinexor, an exportin 1 inhibitor, on opportunistic viruses affecting immunocompromised individuals

2018 ◽  
Author(s):  
Douglas G. Widman ◽  
Savanna Gornisiewicz ◽  
Sharon Shacham ◽  
Sharon Tamir
Keyword(s):  
Small Molecules ◽  
Nuclear Export ◽  
Viral Infections ◽  
Phase 1 ◽  
Dose Range ◽  
Adaptive Immune Response ◽  
Bk Virus ◽  
Healthy Human ◽  
Barr Virus ◽  
Epstein Barr

AbstractInfection of immunocompromised individuals with normally benign opportunistic viruses is a major health burden globally. Infections with viruses such as Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), Kaposi’s sarcoma virus (KSHV), adenoviruses (AdV), BK virus (BKPyV), John Cunningham virus (JCPyV), and human papillomavirus (HPV) are significant concerns for the immunocompromised, including when these viruses exist as a co-infection with human immunodeficiency virus (HIV). These viral infections are more complicated in patients with a weakened immune system, and often manifest as malignancies resulting in significant morbidity and mortality. Vaccination is not an attractive option for these immune compromised individuals due to defects in their adaptive immune response. Verdinexor is part of a novel class of small molecules known as SINE (Selective Inhibitor of Nuclear Export) compounds. These small molecules demonstrate specificity for the nuclear export protein XPO1, to which they bind and block function, resulting in sequestration of XPO1-dependent proteins in the nucleus of the cell. In antiviral screening, verdinexor demonstrated varying levels of efficacy against all of the aforementioned viruses including previously with HIV. Studies by other labs have discussed likely mechanisms of action for verdinexor (ie. XPO-1-dependence) against each virus. GLP toxicology studies suggest that anti-viral activity can be achieved at a tolerable dose range, based on the safety profile of a previous phase 1 clinical trial of verdinexor in healthy human volunteers. Taken together, these results indicate verdinexor has the potential to be a broad spectrum antiviral for immunocompromised subjects for which vaccination is a poor option.

scholarly journals Coevolution of Sites under Immune Selection Shapes Epstein–Barr Virus Population Structure

2019 ◽  
Vol 36 (11) ◽  
pp. 2512-2521 ◽  
Author(s):  
Fanny Wegner ◽  
Florent Lassalle ◽  
Daniel P Depledge ◽  
François Balloux ◽  
Judith Breuer
Keyword(s):  
Epstein Barr Virus ◽  
Viral Infections ◽  
Genetic Recombination ◽  
Adaptive Immune Response ◽  
Immune Selection ◽  
Barr Virus ◽  
Genome Wide ◽  
Epstein Barr ◽  
Globally Distributed ◽  
Genome Wide Linkage Disequilibrium

Abstract Epstein–Barr virus (EBV) is one of the most common viral infections in humans and persists within its host for life. EBV therefore represents an extremely successful virus that has evolved complex strategies to evade the host’s innate and adaptive immune response during both initial and persistent stages of infection. Here, we conducted a comparative genomics analysis on 223 whole genome sequences of worldwide EBV strains. We recover extensive genome-wide linkage disequilibrium (LD) despite pervasive genetic recombination. This pattern is explained by the global EBV population being subdivided into three main subpopulations, one primarily found in East Asia, one in Southeast Asia and Oceania, and the third including most of the other globally distributed genomes we analyzed. Additionally, sites in LD were overrepresented in immunogenic genes. Taken together, our results suggest that host immune selection and local adaptation to different human host populations has shaped the genome-wide patterns of genetic diversity in EBV.

scholarly journals Epstein-Barr Virus and Human Adenovirus Viremia in Renal Tumors Is Associated with Histological Features of Malignancy

2020 ◽  
Vol 9 (10) ◽  
pp. 3195
Author(s):  
Piotr Kryst ◽  
Sławomir Poletajew ◽  
Aleksandra Wyczałkowska-Tomasik ◽  
Stefan Gonczar ◽  
Maciej Wysocki ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Viral Infections ◽  
Clinical Course ◽  
Human Adenovirus ◽  
Bk Virus ◽  
Renal Tumors ◽  
High Grade ◽  
Term Survival ◽  
Barr Virus ◽  
Epstein Barr

Background: There is growing evidence that viral infections may impact the risk and clinical course of malignancies, including solid tumors. The aim of this study was to assess the possible association of selected chronic/latent viral infections with the clinical course of renal cell carcinoma (RCC). Methods: In this prospective study we enrolled 27 patients undergoing partial or radical nephrectomy due to the histologically confirmed RCC and followed them up for one year post-operation. Isolation of the nucleic acids was performed using the NucleoSpin Tissue Kit (Macherey-Nagel, Düren, Germany) from tumor tissue and using the EZ1 Virus Mini Kit v2.0 from plasma. The number of viral copies of human adenovirus (ADV), herpes simplex virus HSV-1 and HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK virus (BKV) and John Cunningham virus (JCV) in the tissue and plasma was assessed with real-time PCR. Results: Viral infections were diagnosed in ten patients (37.0%), including three ADV cases (11.1%) and eight EBV cases (29.6%). Infected patients tended to be significantly older (71.3 vs. 57.6 years, p < 0.05), more commonly presented with chronic renal disease (OR 2.4, p < 0.05), diabetes (OR 4.2, p < 0.05) and overweight (OR 2.0, p < 0.05). Regarding oncological data, infected patients were found to have a higher rate of high-grade cancers (OR 5.0, p < 0.05) and a higher rate of papillary RCCs (OR 8.3, p < 0.05). Status of viral infections had no influence on the clinical cancer stage, surgical procedure or survival. Conclusions: EBV and ADV infections are common in renal cancer patients and increase the risk of high-grade RCC presence. While there is no significant impact on short term survival, further studies are needed to assess the relevance of these findings in a long run.

scholarly journals Epstein-Barr virus and human adenovirus viremia in renal tumors is associated with histological features of kidney cancer

2020 ◽  
Author(s):  
Piotr Kryst ◽  
Sławomir Poletajew ◽  
Aleksandra Wyczałkowska-Tomasik ◽  
Stefan Gonczar ◽  
Maciej Wysocki ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Viral Infections ◽  
Clinical Course ◽  
Human Adenovirus ◽  
Bk Virus ◽  
Renal Tumors ◽  
High Grade ◽  
Term Survival ◽  
Barr Virus ◽  
Epstein Barr

Abstract Background. There is a growing evidence that viral infections may impact the risk and clinical course of malignancies, including solid tumors. The aim of this study was to assess the possible association of selected chronic / latent viral infections with the clinical course of renal cell carcinoma (RCC).Methods. In this prospective study we enrolled 27 patients undergoing partial or radical nephrectomy due to the histologically confirmed RCC and followed them up for one year post-operation. Isolation of the nucleic acids of human adenovirus (ADV), herpes simplex virus HSV-1 and HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK virus (BKV) and John Cunningham virus (JCV) from tumor tissue was performed using the NucleoSpin Tissue Kit (Macherey-Nagel, Düren, Germany) or EZ1 Virus Mini Kit (Qiagen, Hilden, Germany). The number of viral copies in the tissue was assessed with the real-time PCR.Results. Viral infections were diagnosed in ten patients (37.0%), including three ADV cases (11.1%) and eight EBV cases (29.6%). Infected patients tended to be significantly older (71.3 vs. 57.6 years, p < 0.05), more commonly presented with chronic renal disease (OR 2.4, p < 0.05), diabetes (OR 4.2, p < 0.05) and overweight (OR 2.0, p < 0.05). Regarding oncological data, infected patients were found to have a higher rate of high-grade cancers (OR 5.0, p < 0.05) and a higher rate of papillary RCCs (OR 8.3, p < 0.05). Status of viral infections had no influence on the clinical cancer stage, surgical procedure or survival.Conclusions. EBV and ADV infections are common in renal cancer patients and increase the risk of high-grade RCC presence. While there is no significant impact on short term survival, further studies are needed to assess the relevance of these findings in a long run.Trial registration. Medical University of Warsaw KB/37/2017

scholarly journals Double-Stranded DNA (dsDNA) Viral Infections Among Allogeneic Hematopoietic Cell Transplant (HCT) Recipients in the First Year after Transplant

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3296-3296 ◽  
Author(s):  
Vernon F Schabert ◽  
Essy Mozaffari ◽  
Yi-Chien Lee ◽  
Roman Casciano
Keyword(s):  
Viral Infection ◽  
Viral Infections ◽  
Bk Virus ◽  
First Year ◽  
Cell Transplant ◽  
Post Transplant ◽  
Allogeneic Hct ◽  
Barr Virus ◽  
Epstein Barr ◽  
One Year

Abstract Introduction: Double-stranded DNA (dsDNA) viral infections (including cytomegalovirus, adenoviruses, BK virus, and Epstein-Barr virus) can lead to significant morbidity and mortality among immunocompromised patients following allogeneic hematopoietic stem cell transplant (HCT). The lack of a broad-spectrum antiviral with the safety and tolerability to prevent viral infections poses management challenges for patients at risk of multiple dsDNA viral infections. Using a large US insurance claims database, this study describes the incidence of dsDNA viral infections and co-infections among allogeneic HCT recipients. Methods: The MarketScan Research Databases were used to identify commercial and Medicare enrollees with an ICD-9 or CPT procedure code for an allogeneic HCT between 7/1/2009 and 6/30/2014. Eligible patients were required to have 365 days of health plan enrollment prior to HCT, but no minimum enrollment was required post-HCT. Incidence of cytomegalovirus (CMV), adenovirus (AdV), BK virus, Epstein-Barr virus, herpes simplex, varicella zoster, and other dsDNA virus infection was measured from the date of the transplant until one year post-transplant. The rates of infection with two dsDNA viral infections or three or more dsDNA viral infections were assessed, and in-hospital mortality or transfer to hospice services within one year of transplant was reported by the number of observed dsDNA viral infection. Results: We identified 3,035 allogeneic HCT patients (mean age 47.3 years, 56.9% male), including 30.4% (n=924) with at least one dsDNA viral infection within the first year post-transplant. Of these, 69.2% had CMV infection (n=639), 5.4% had AdV infection (n=50), and 10.3% had BK virus infection (n=95). Among patients with a reported dsDNA viral infection, 17.6% (n=163) had more than one dsDNA viral infection, including 14.6% (n=135) with two dsDNA viral infections and 3.0% (n=28) with three or more viral infections. A statistically significant increase in the rate of in-hospital death or transfer to hospice within the first year post-transplant was observed for patients with reported dsDNA viral infection vs those without. Specifically, the rate of in-hospital mortality/transfer to hospice increased from 14.9% (315/2111) for patients without a reported dsDNA viral infection to 19.2% (146/761, p=0.0060) with one dsDNA viral infection, 23.0% (31/135, p=0.0121) for patients with two dsDNA viral infections, and 35.7% (10/28, p=0.0023) for patients with three or more dsDNA viral infections. Conclusions: A substantial proportion of allogeneic HCT recipients with a dsDNA viral infection have two or more dsDNA viral infections. Diagnoses on insurance claims may underestimate true incidence of dsDNA viral infection and co-infection. Mortality risk increases significantly with the number of dsDNA viral infections. Availability of a safe and well-tolerated broad spectrum antiviral for prevention of primary or reactivation infections could potentially reduce the morbidity and mortality associated with dsDNA viral infections and their significant sequelae. Disclosures Schabert: LASER Analytica: Employment. Mozaffari:Chimerix Inc.: Employment, Equity Ownership. Lee:LASER Analytica: Employment. Casciano:LASER Analytica: Employment.

Acute Pharyngitis: Etiology and Diagnosis

PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 949-954
Author(s):  
Alan L. Bisno
Keyword(s):  
Herpes Simplex ◽  
Influenza A ◽  
Epstein Barr Virus ◽  
Viral Infections ◽  
Clinical Manifestations ◽  
Acute Pharyngitis ◽  
Herpesvirus Type ◽  
Barr Virus ◽  
Epstein Barr

Acute pharyngitis may be caused by a wide variety of microbial agents (Table 1). The relative importance of each of these agents varies greatly depending on a number of epidemiologic factors, including age of the patient, season of the year, and geographic locale. Viruses Most cases of acute pharyngitis are viral in etiology and involve the pharynx as well as other portions of the respiratory tract as manifestations of the common cold, influenza, or croup. Examples include the rhinoviruses, coronaviruses, influenza A and B, and the parainfluenza viruses. Certain viral infections causing sore throat may exhibit clinical manifestations that are rather distinctive. Examples include enteroviruses (herpangina due to Coxsackie A), Epstein-Barr virus (infectious mononucleosis), cytomegalovirus (cytomegalovirus mononucleosis), adenovirus (pharyngoconjunctival fever, acute respiratory disease of military recruits), and herpes simplex virus (pharyngitis, gingivitis, and stomatitis). In many instances, however, the illnesses caused by these agents may overlap so broadly with that of streptococcal pharyngitis as to be clinically indistinguishable. Thus, Epstein-Barr virus, adenovirus, and herpes virus may all cause fever, exudative pharyngitis, and cervical adenitis. Several studies have documented the role of primary herpesvirus type 1 infection as a cause of acute pharyngitis in college students.1-4 Herpesvirus type 2 can occasionally cause a similar illness as a consequence of oral-genital sexual contact.5 Although herpesvirus infections may involve the anterior oral cavity (vesicular or ulcerative gingivostomatitis) as well as the posterior pharynx, they do not routinely do so. Only about one-fourth of students with culturally and serologically proven primary herpes simplex type 1 pharyngitis studied by Glezen et al,2 for example, had gingivostomatitis.

scholarly journals Three Severe Cases of Viral Infections with Post-Kidney Transplantation Successfully Confirmed by Polymerase Chain Reaction and Flow Cytometry

2018 ◽  
Vol 8 (3) ◽  
pp. 198-206
Author(s):  
Keita Nakanishi ◽  
Hiroshi Kaito ◽  
Miki Ogi ◽  
Denshi Takai ◽  
Junya Fujimura ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Polymerase Chain Reaction ◽  
Kidney Transplantation ◽  
Viral Infections ◽  
Specific Treatment ◽  
Epstein Barr Virus Infection ◽  
Chain Reaction ◽  
Barr Virus ◽  
Polymerase Chain ◽  
Epstein Barr

Viral infections in patients with post-kidney transplantation are often difficult to diagnose as well as treat. We herein report three cases with severe viral infections after kidney transplantation. All their causative pathogens could be detected promptly by polymerase chain reaction and flow cytometry during the early stages of infection. These examinations would also be of great use to monitor therapeutic responses and disease activity. It is indeed true that no specific treatment is available for most of the viral infections, but we should be aware that some infections, such as Epstein-Barr virus infection, can be treatable with prompt and specific treatment, such as rituximab.

scholarly journals Pancytopenia Secondary to SARS-CoV 2 Infection-A Case Reprt

2021 ◽  
Author(s):  
Neeraj Sharma ◽  
Rajat Shukla ◽  
Rachna Warrier ◽  
Kunal Kumar ◽  
Nalin Singh ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Blood Cells ◽  
Epstein Barr Virus ◽  
Viral Infections ◽  
Parvovirus B19 ◽  
Rare Complication ◽  
Elderly Male ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Epstein Barr

Abstract Pancytopenia is a condition when person has low count of all three types of blood cells causing a triage of anemia, leukopenia and thrombocytopenia. It should not be considered as a disease in itself but rather the sign of a disease that needs to be further evaluated. Among the various causes, viral infections like Human Immunodeficiency Virus, Cytomegalovirus, Epstein-Barr virus and Parvovirus B19 have been implicated. Pancytopenia is a rare complication and not commonly seen in patients with COVID 19 disease. Here, we report a case of pancytopenia in previously immunocompetent elderly male patient with SARS-CoV2 infection.

scholarly journals Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment

2012 ◽  
pp. 305-311 ◽  
Author(s):  
María Lilia Diaz Betancourth ◽  
Julio Cesar Klinger ◽  
Victoria Eugenia Niño
Keyword(s):  
Human Immunodeficiency Virus ◽  
Epstein Barr Virus ◽  
Herpes Virus ◽  
Viral Infections ◽  
Human Herpes ◽  
Barr Virus ◽  
Human Herpes Virus ◽  
Immunodeficiency Virus ◽  
Epstein Barr ◽  
Herpès Virus

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immu­nodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lym­phocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diag­nosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings’ health.

scholarly journals The prevalence of the most important viral infections in renal transplant recipients in Serbia

2012 ◽  
Vol 64 (4) ◽  
pp. 1285-1296 ◽  
Author(s):  
Maja Cupic ◽  
Ivana Lazarevic ◽  
Vera Pravica ◽  
Ana Banko ◽  
Danijela Karalic ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Viral Infections ◽  
Opportunistic Infections ◽  
Uv Light ◽  
Molecular Testing ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Chi Square ◽  
Barr Virus ◽  
Epstein Barr

Viruses are the main cause of opportunistic infections after kidney transplantation. The aim of this study was to determine the prevalence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), B. K. virus (BKV) and John Cunningham virus (JCV) infections in renal transplant recipients (RTR). This retrospective study of 112 RTR investigated the presence of CMV, EBV and polyomaviruses DNA in plasma and/or urine by PCR. The visualization of PCR products was performed by electrophoresis on 2% agarose gel stained with ethidium bromide and photographed under a UV light. The chi-square test was used for statistical analysis. CMV DNA was detected in 14/112 (12.5%), EBV DNA in 4/49 (8.16%), BKV DNA in 10/31 (32.26%) and JCV DNA in 3/31 (9.68%) RTR. These results show that CMV infection is more often present in RTR compared to other investigated viral infections. In the light of these results, molecular testing could be useful in identifying recipients at high risk of symptomatic post-transplant viral infection.

scholarly journals Gammaherpesvirus infection licenses age-associated B cells for pathogenicity in MS and EAE

2021 ◽  
Author(s):  
Isobel C. Mouat ◽  
Jessica R. Allanach ◽  
Vina Fan ◽  
Anna M. Girard ◽  
Iryna Shanina ◽  
...  
Keyword(s):  
B Cells ◽  
Viral Infection ◽  
Viral Infections ◽  
Autoimmune Encephalomyelitis ◽  
Barr Virus ◽  
Ebv Infection ◽  
Latent Viral Infection ◽  
Epstein Barr ◽  
Gammaherpesvirus 68 ◽  
Experimental Autoimmune

While age-associated B cells (ABCs) are known to expand and persist following viral infection and during autoimmunity, their interactions are yet to be studied together in these contexts. Epstein-Barr virus (EBV) infection has long been implicated in multiple sclerosis (MS), and it is not known whether ABCs could play a role in mediating viral contribution to autoimmunity. Here, we show that the circulating ABC population is expanded in people with MS and that EBV infection and MS status differentially impact the circulating ABC phenotype. We then directly compared ABCs during viral infection and autoimmunity using mouse models of EBV, gammaherpesvirus 68 (γHV68), and MS, experimental autoimmune encephalomyelitis (EAE). We observed that splenic ABCs are expanded in a sex-biased manner during both latent virus infection and EAE, and each event drives the ABC population to opposing phenotypes. We have previously shown that latent γHV68 infection exacerbates EAE and here we show that mice lacking ABCs fail to display γHV68-enhanced disease. Collectively, these findings indicate that latent viral infection and central nervous system autoimmunity differentially impact the ABC population and suggests that viral infections such as EBV prime ABCs to contribute pathogenically in MS.

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