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1.
Virol J ; 18(1): 180, 2021 09 05.
Article in English | MEDLINE | ID: covidwho-1388778

ABSTRACT

BACKGROUND: Covid-19 has the respiratory tract as the main target of infection, and patients present mainly dyspnea, pneumonia, dry cough, and fever. Nevertheless, organs outside the respiratory tract had been reported in recent studies, including the gastrointestinal tract and liver. The host innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through their pattern recognition receptor (PRRs). Toll-like receptor 7 (TLR-7) is a pattern recognition receptor recognizing ssRNA (SARS-CoV-2 is an ssRNA). Polymorphisms are characterized by two or more alternative forms of a distinct phenotype in the same population. Polymorphisms in tlrs genes can negatively influence the immune response to infectious diseases. There are several references in the literature to non-synonymous single nucleotide (rs) polymorphisms related to several genes. Some of them are important for the innate immunity, as rs 179008 (tlr-7), rs3775291 (tlr3), rs8177374 (tir domain-containing adaptor protein, tirap), rs1024611 (monocyte chemoattractant protein-1, mcp-1) and rs61942233 (2'-5'-oligoadenylate synthase-3, oas-3). CASE PRESENTATION: We identified a 5-year-old-male child with gastrointestinal symptoms and fever presenting acholic stool and jaundice, who was positive for SARS-CoV-2 IgM, IgA, and IgG and presenting the Gln11Leu rs 179008 in tlr-7. The child presented high levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, C-reactive protein, D-dimer, gamma-glutamyl transferase, alkaline phosphatase, and was negative for serological tests for hepatitis A, B, C, E, HIV 1 and 2, herpes virus, cytomegalovirus, Epstein-Barr virus, and negative for RTqPCR for Influenza A and B, RSV and SARS-CoV-2. We also investigated other SNPs in the tlr-3 (rs3775291), tirap (rs8177374), mcp-1 (rs1024611), and oas-3 (rs61942233) genes, and no mutation was detected. After an interview with the child's caregivers, any possible accidental ingestion of drugs or hepatotoxic substances was ruled out. CONCLUSION: To our knowledge, this is the first report of a SARS-CoV-2 caused hepatitis in a male child that has the tlr-7 Gln11Leu rs 179008, which could impair an efficient initial immune response. The knowledge of the patient's immune deficiency could improve the treatment to correct this deficiency with specific medications.


Subject(s)
COVID-19/genetics , COVID-19/virology , Hepatitis, Viral, Human/genetics , Hepatitis, Viral, Human/virology , Toll-Like Receptor 7/genetics , Antibodies, Viral/blood , COVID-19/immunology , Child, Preschool , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/virology , Feces/virology , Hepatitis, Viral, Human/immunology , Herpesvirus 4, Human/isolation & purification , Humans , Immunity, Innate , Influenza, Human , Male , Polymorphism, Single Nucleotide , SARS-CoV-2/isolation & purification
2.
OMICS ; 25(6): 358-371, 2021 06.
Article in English | MEDLINE | ID: covidwho-1243453

ABSTRACT

About a tenth of all cancers are caused by viruses or associated with viral infection. Recent global events including the coronavirus disease-2019 (COVID-19) pandemic means that human encounter with viruses is increased. Cancer development in individuals with viral infection can take many years after infection, demonstrating that the involvement of viruses in cancer development is a long and complex process. This complexity emanates from individual genetic heterogeneity and the many steps involved in cancer development owing to viruses. The process of tumorigenesis is driven by the complex interaction between several viral factors and host factors leading to the creation of a tumor microenvironment (TME) that is ideal and promotes tumor formation. Viruses associated with human cancers ensure their survival and proliferation through activation of several cellular processes including inflammation, migration, and invasion, resistance to apoptosis and growth suppressors. In addition, most human oncoviruses evade immune detection and can activate signaling cascades including the PI3K-Akt-mTOR, Notch and Wnt pathways associated with enhanced proliferation and angiogenesis. This expert review examines and synthesizes the multiple biological factors related to oncoviruses, and the signaling cascades activated by these viruses contributing to viral oncogenesis. In particular, I examine and review the Epstein-Barr virus, human papillomaviruses, and Kaposi's sarcoma herpes virus in a context of cancer pathogenesis. I conclude with a future outlook on therapeutic targeting of the viruses and their associated oncogenic pathways within the TME. These anticancer strategies can be in the form of, but not limited to, antibodies and inhibitors.


Subject(s)
Epstein-Barr Virus Infections/virology , Neoplasms/virology , Papillomavirus Infections/virology , Retroviridae Infections/virology , Retroviridae/physiology , Sarcoma, Kaposi/virology , Tumor Virus Infections/virology , Alphapapillomavirus/physiology , Carcinogenesis , Cell Transformation, Viral , Epstein-Barr Virus Infections/pathology , Herpesvirus 4, Human/physiology , Herpesvirus 8, Human/physiology , Humans , Molecular Targeted Therapy , Neoplasms/pathology , Neoplasms/therapy , Papillomavirus Infections/pathology , Retroviridae Infections/pathology , Sarcoma, Kaposi/pathology , Signal Transduction , Tumor Microenvironment , Tumor Virus Infections/pathology
3.
Sci Rep ; 11(1): 10902, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243311

ABSTRACT

The objective of this study was to detect the Epstein-Barr virus (EBV) coinfection in coronavirus disease 2019 (COVID-19). In this retrospective single-center study, we included 67 COVID-19 patients with onset time within 2 weeks in Renmin Hospital of Wuhan University from January 9 to February 29, 2020. Patients were divided into EBV/SARS-CoV-2 coinfection group and SARS-CoV-2 infection alone group according to the serological results of EBV, and the characteristics differences between the two groups were compared. The median age was 37 years, with 35 (52.2%) females. Among these COVID-19 patients, thirty-seven (55.2%) patients were seropositive for EBV viral capsid antigen (VCA) IgM antibody. EBV/SARS-CoV-2 coinfection patients had a 3.09-fold risk of having a fever symptom than SARS-CoV-2 infection alone patients (95% CI 1.11-8.56; P = 0.03). C-reactive protein (CRP) (P = 0.02) and the aspartate aminotransferase (AST) (P = 0.04) in EBV/SARS-CoV-2 coinfection patients were higher than that in SARS-CoV-2 infection alone patients. EBV/SARS-CoV-2 coinfection patients had a higher portion of corticosteroid use than the SARS-CoV-2 infection alone patients (P = 0.03). We find a high incidence of EBV coinfection in COVID-19 patients. EBV/SARS-CoV-2 coinfection was associated with fever and increased inflammation. EBV reactivation may associated with the severity of COVID-19.


Subject(s)
Antibodies, Viral/blood , COVID-19/pathology , Epstein-Barr Virus Infections/pathology , Herpesvirus 4, Human/isolation & purification , Adrenal Cortex Hormones/therapeutic use , Adult , Aspartate Aminotransferases/blood , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/virology , Capsid Proteins/immunology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/drug therapy , Epstein-Barr Virus Infections/virology , Female , Fever/etiology , Herpesvirus 4, Human/immunology , Herpesvirus 4, Human/metabolism , Humans , Immunoglobulin M/blood , Male , Middle Aged , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index
4.
PLoS Pathog ; 17(4): e1009041, 2021 04.
Article in English | MEDLINE | ID: covidwho-1231262

ABSTRACT

Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus with latent and lytic cycles. EBV replicates in the stratified epithelium but the nasopharynx is also composed of pseudostratified epithelium with distinct cell types. Latent infection is associated with nasopharyngeal carcinoma (NPC). Here, we show with nasopharyngeal conditionally reprogrammed cells cultured at the air-liquid interface that pseudostratified epithelial cells are susceptible to EBV infection. Donors varied in susceptibility to de novo EBV infection, but susceptible cultures also displayed differences with respect to pathogenesis. The cultures from one donor yielded lytic infection but cells from two other donors were positive for EBV-encoded EBERs and negative for other lytic infection markers. All cultures stained positive for the pseudostratified markers CK7, MUC5AC, α-tubulin in cilia, and the EBV epithelial cell receptor Ephrin receptor A2. To define EBV transcriptional programs by cell type and to elucidate latent/lytic infection-differential changes, we performed single cell RNA-sequencing on one EBV-infected culture that resulted in alignment with many EBV transcripts. EBV transcripts represented a small portion of the total transcriptome (~0.17%). All cell types in the pseudostratified epithelium had detectable EBV transcripts with suprabasal cells showing the highest number of reads aligning to many EBV genes. Several restriction factors (IRF1, MX1, STAT1, C18orf25) known to limit lytic infection were expressed at lower levels in the lytic subcluster. A third of the differentially-expressed genes in NPC tumors compared to an uninfected pseudostratified ALI culture overlapped with the differentially-expressed genes in the latent subcluster. A third of these commonly perturbed genes were specific to EBV infection and changed in the same direction. Collectively, these findings suggest that the pseudostratified epithelium could harbor EBV infection and that the pseudostratified infection model mirrors many of the transcriptional changes imposed by EBV infection in NPC.


Subject(s)
Epithelial Cells/virology , Epstein-Barr Virus Infections/virology , Host-Pathogen Interactions/immunology , Nasopharyngeal Neoplasms/virology , Carcinoma/metabolism , Carcinoma/virology , Epithelial Cells/metabolism , Epithelium/metabolism , Epithelium/virology , Epstein-Barr Virus Infections/metabolism , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/pathogenicity , Humans , Nasopharyngeal Carcinoma/virology , RNA, Viral/genetics
5.
Clin Immunol ; 227: 108727, 2021 06.
Article in English | MEDLINE | ID: covidwho-1193258

ABSTRACT

With the global spread of coronavirus disease 2019 (COVID-19), the important role of natural killer (NK) cells in the control of various viral infections attracted more interest, via non-specific activation, such as antibody-dependent cell-mediated cytotoxicity (ADCC) and activating receptors, as well as specific activation, such as memory-like NK generation. In response to different viral infections, NK cells fight viruses in different ways, and different NK subsets proliferate. For instance, cytomegalovirus (CMV) induces NKG2C + CD57 + KIR+ NK cells to expand 3-6 months after hematopoietic stem cell transplantation (HSCT), but human immunodeficiency virus (HIV) induces KIR3DS1+/KIR3DL1 NK cells to expand in the acute phase of infection. However, the similarities and differences among these processes and their molecular mechanisms have not been fully discussed. In this article, we provide a summary and comparison of antiviral mechanisms, unique subset expansion and time periods in peripheral blood and tissues under different conditions of CMV, HIV, Epstein-Barr virus (EBV), COVID-19 and hepatitis B virus (HBV) infections. Accordingly, we also discuss current clinical NK-associated antiviral applications, including cell therapy and NK-related biological agents, and we state the progress and future prospects of NK cell antiviral treatment.


Subject(s)
COVID-19/immunology , COVID-19/virology , Host Microbial Interactions/immunology , Killer Cells, Natural/immunology , Antibody-Dependent Cell Cytotoxicity , COVID-19/blood , Cytomegalovirus/immunology , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/virology , HIV/immunology , HIV Infections/blood , HIV Infections/immunology , HIV Infections/virology , Hepatitis B/blood , Hepatitis B/immunology , Hepatitis B/virology , Hepatitis B virus/immunology , Herpesvirus 4, Human/immunology , Humans , SARS-CoV-2/immunology , Toll-Like Receptors/metabolism
6.
Diagn Microbiol Infect Dis ; 100(1): 115313, 2021 May.
Article in English | MEDLINE | ID: covidwho-1065007

ABSTRACT

OBJECTIVES: To evaluate the diagnostic performances of four SARS-CoV-2 IgG antibody immunoassays. METHODS: Following immunoassays were studied: Abbott's SARS-CoV-2 IgG assay, Diasorin's Liaison SARS-CoV-2 S2/S2 IgG assay, Euroimmun's Anti-SARS-CoV-2 IgG ELISA, and Roche's Elecsys Anti-SARS-CoV-2 assay. Specificity was retrospectively evaluated with 38 samples from 2019. Sensitivity samples (n = 147) were taken from SARS-CoV-2 real-time PCR-positive patients who developed COVID-19 symptoms ten days earlier. RESULTS: Mean specificity was 96.6%. Mean sensitivity was 62.7% from ten days after onset of symptoms, 84.4% from 15 days after onset of symptoms, and 87.5% from 20 days after onset of symptoms. CONCLUSIONS: Specificity was high, while Abbott and Roche were 100% specific. Sensitivity increased over time, with Abbott and Roche having the highest sensitivity at all time points with ≥90% from 20 days after symptoms' onset. These findings may assist in selecting SARS-CoV-2 IgG antibody immunoassays for additional diagnostics, epidemiological research, and vaccine development.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , Immunoassay/methods , Adolescent , Adult , Aged , Child , Child, Preschool , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/virology , Female , Humans , Immunoglobulin G/blood , Infant , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , Sensitivity and Specificity , Young Adult
7.
Int J Infect Dis ; 104: 315-319, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-988038

ABSTRACT

OBJECTIVES: The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. METHODS: A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. RESULTS: Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p<0.05). In contrast, B cell count was significantly increased in ICU patients (p=0.0172). CONCLUSIONS: A correlation between reduced CD8+ T cells and NK counts, EBV DNA levels and COVID-19 severity was observed. Other opportunistic viral infections were not observed. The relationship between EBV load and COVID-19 severity should be further evaluated in longitudinal studies.


Subject(s)
COVID-19/complications , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/isolation & purification , SARS-CoV-2 , Viral Load , Aged , Aged, 80 and over , CD8-Positive T-Lymphocytes/virology , COVID-19/virology , DNA, Viral/analysis , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Female , Herpesvirus 4, Human/genetics , Humans , Intensive Care Units , Killer Cells, Natural/virology , Lymphocyte Count , Lymphocyte Subsets/virology , Male , Middle Aged , Opportunistic Infections , Real-Time Polymerase Chain Reaction
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