The viral expression and immune status in human cancers and insights into novel biomarkers of immunotherapy

Abstract Background Viral infections are prevalent in human cancers and they have great diagnostic and theranostic values in clinical practice. Recently, their potential of shaping the tumor immune microenvironment (TIME) has been related to the immunotherapy of human cancers. However, the landscape of viral expressions and immune status in human cancers remains incompletely understood. Methods We developed a next-generation sequencing (NGS)-based pipeline to detect viral sequences from the whole transcriptome and used machine learning algorithms to classify different TIME subtypes. Results We revealed a pan-cancer landscape of viral expressions in human cancers where 9 types of viruses were detected in 744 tumors of 25 cancer types. Viral infections showed different tissue tendencies and expression levels. Multi-omics analyses further revealed their distinct impacts on genomic, transcriptomic and immune responses. Epstein-Barr virus (EBV)-infected stomach adenocarcinoma (STAD) and Human Papillomavirus (HPV)-infected head and neck squamous cell carcinoma (HNSC) showed decreased genomic variations, significantly altered gene expressions, and effectively triggered anti-viral immune responses. We identified three TIME subtypes, in which the “Immune-Stimulation” subtype might be the promising candidate for immunotherapy. EBV-infected STAD and HPV-infected HNSC showed a higher frequency of the “Immune-Stimulation” subtype. Finally, we constructed the eVIIS pipeline to simultaneously evaluate viral infection and immune status in external datasets. Conclusions Viral infections are prevalent in human cancers and have distinct influences on hosts. EBV and HPV infections combined with the TIME subtype could be promising biomarkers of immunotherapy in STAD and HNSC, respectively. The eVIIS pipeline could be a practical tool to facilitate clinical practice and relevant studies.

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IMMUNE STATUS OF EPSTEIN - BARR VIRUS-INFECTED CHILDREN WITH SECRETORY MIDDLE OTITIS

International Medical Journal ◽

10.37436/2308-5274-2019-3-11 ◽

2020 ◽

pp. 60-64

Author(s):

Alina Volodymyrivna Chumakova ◽

Yuliia Viktorivna Lozova

Keyword(s):

Otitis Media ◽

Epstein Barr Virus ◽

Immune Status ◽

Enzyme Analysis ◽

Comprehensive Treatment ◽

Upper Respiratory Tract ◽

Adequate Treatment ◽

Barr Virus ◽

Cell Immunity ◽

Epstein Barr

Recently the role of herpes viruses in an aggravation of inflammatory diseases of the upper respiratory tract, in particular, herpes simplex virus and Epstein − Barr virus, has become increasingly evident in otorhynolaryngology practice. To determine the extent of infection with Epstein − Barr virus and to study the immunogram of the first level for the children with secretory otitis media, 48 patients aged 3−9 years were examined for the purpose of an adequate treatment. Infection was revealed by serological diagnosis (enzyme immunoassay) with the determination of IgM to capsid complex (VCA) and IgG to early antigen (EA). Level 1 immunograms were also determined by immune enzyme analysis. Children with secretive middle otitis (22.9 %) were infected with Epstein − Barr virus, corresponding to an acute phase of the disease, as well as they had a reduce cell immunity. All children received comprehensive treatment for secretory middle otitis. It was concluded about the need for children with middle otitis to be screened for an infection with the Epstein−Barr virus and treated conservatively by an immunologist. Key words: secretory middle otitis media, etiology of Epstein − Barr virus, immune status of children, treatment.

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Acute Pharyngitis: Etiology and Diagnosis

PEDIATRICS ◽

10.1542/peds.97.6.949 ◽

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.

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

Case Reports in Nephrology and Dialysis ◽

10.1159/000493092 ◽

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.

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P.021 Native conformation and wild-type sequence of Epstein–Barr virus protein BARF1 are essential for humoral immune responses to BARF1 in nasopharyngeal carcinoma patients

Journal of Clinical Virology ◽

10.1016/s1386-6532(08)70084-2 ◽

2009 ◽

Vol 44 ◽

pp. S21

Author(s):

E.K. Hoebe ◽

S.H. Hutajulu ◽

D.K. Paramita ◽

A.E. Greijer ◽

J.M. Middeldorp

Keyword(s):

Immune Responses ◽

Epstein Barr Virus ◽

Virus Protein ◽

Wild Type ◽

Native Conformation ◽

Humoral Immune ◽

Barr Virus ◽

Humoral Immune Responses ◽

Epstein Barr ◽

Type Sequence

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Manipulation of immune responses by Epstein–Barr virus

Virus Research ◽

10.1016/s0168-1702(02)00121-1 ◽

2002 ◽

Vol 88 (1-2) ◽

pp. 71-86 ◽

Cited By ~ 27

Author(s):

Victor Levitsky ◽

Maria G Masucci

Keyword(s):

Immune Responses ◽

Epstein Barr Virus ◽

Barr Virus ◽

Epstein Barr

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

10.21203/rs.3.rs-657352/v1 ◽

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.

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

Colombia Medica ◽

10.25100/cm.v43i4.1159 ◽

2012 ◽

pp. 305-311 ◽

Cited By ~ 3

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.

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

Archives of Biological Sciences ◽

10.2298/abs1204285c ◽

2012 ◽

Vol 64 (4) ◽

pp. 1285-1296 ◽

Cited By ~ 1

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.

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

10.1101/2021.07.22.453263 ◽

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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