Nejvíce citovaný článek - PubMed ID 24214630
Seroprevalence rates of BKV, JCV, and MCPyV polyomaviruses in the general Czech Republic population
Tumors of infectious origin globally represent 13%. Oncogenic DNA viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV) are responsible for approximately 60% of these tumors. These oncoviruses are extensively studied to understand their role in cancer development, particularly through viral genome integration into the host DNA. Retroviruses require integration mediated by viral integrase for persistence, whereas DNA oncoviruses do not need integration for replication; instead, integration occurs incidentally. This process often targets fragile sites in the human genome, causing structural rearrangements that disrupt genes, activate proto-oncogenes, and increase genomic instability, all contributing to tumorigenesis. Integration near promoter regions and active genes is closely linked to carcinogenesis, highlighting its importance in developing diagnostic and therapeutic strategies. This review summarizes viral integration's role in oncogenesis, mechanisms of integration, and methods to study this process, focusing on DNA tumor viruses such as HBV, EBV, HPV, and Merkel cell polyomavirus.
- Klíčová slova
- Epstein-Barr virus, hepatitis B virus, human papillomavirus, integration, virus,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BK polyomavirus (BKPyV) often reactivates after kidney transplantation, causing BKPyV-associated nephropathy (BKPyVAN) in 1%-10% of cases with a potential detrimental effect on allograft survival. Kidney transplant recipients are regularly screened for BKPyV DNA in plasma. As this strategy may not always reduce the risk of BKPyVAN, other predictive markers are needed. To evaluate the role of pretransplant BKPyV-specific antibody, 210 kidney transplant recipients and 130 donors were screened for BKPyV DNA and BKPyV-specific antibodies. We found that the donor BKPyV immunoglobulin G (IgG) seroprevalence and antibody level were strongly associated with BKPyV-DNAemia and BKPyVAN, although multivariant analysis found the presence of anti-BKPyV-specific antibodies as a predictive factor only for BKPyV-DNAemia. The pretransplant recipient status had no effect on posttransplant BKPyV-DNAemia and BKVAN. BKPyV IgG levels remained stable in BKPyV-negative recipients during 1-year follow-up, while a considerable increase was observed in BKPyV-positive patients. The presence of anti-BKPyV-specific antibodies in kidney allograft donors is a good and reliable predictive marker for posttransplant BKPyV replication with relevance to risk stratification in transplant recipients.
- Klíčová slova
- BK polyomavirus (BKPyV), BKPyV-associated nephropathy, kidney transplantation, seroprevalence, seroreactivity,
- MeSH
- imunoglobulin G MeSH
- intersticiální nefritida * komplikace MeSH
- lidé MeSH
- polyomavirové infekce * MeSH
- séroepidemiologické studie MeSH
- transplantace ledvin * škodlivé účinky MeSH
- virus BK * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- imunoglobulin G MeSH
DNA virus infections are often lifelong and can cause serious diseases in their hosts. Their recognition by the sensors of the innate immune system represents the front line of host defence. Understanding the molecular mechanisms of innate immunity responses is an important prerequisite for the design of effective antivirotics. This review focuses on the present state of knowledge surrounding the mechanisms of viral DNA genome sensing and the main induced pathways of innate immunity responses. The studies that have been performed to date indicate that herpesviruses, adenoviruses, and polyomaviruses are sensed by various DNA sensors. In non-immune cells, STING pathways have been shown to be activated by cGAS, IFI16, DDX41, or DNA-PK. The activation of TLR9 has mainly been described in pDCs and in other immune cells. Importantly, studies on herpesviruses have unveiled novel participants (BRCA1, H2B, or DNA-PK) in the IFI16 sensing pathway. Polyomavirus studies have revealed that, in addition to viral DNA, micronuclei are released into the cytosol due to genotoxic stress. Papillomaviruses, HBV, and HIV have been shown to evade DNA sensing by sophisticated intracellular trafficking, unique cell tropism, and viral or cellular protein actions that prevent or block DNA sensing. Further research is required to fully understand the interplay between viruses and DNA sensors.
- Klíčová slova
- DNA sensing, DNA viruses, IFI16, IFN, STING, TLR9, cGAS, inflammasome, innate immunity, p204/Ifi-204,
- MeSH
- DNA virů metabolismus MeSH
- Herpesviridae * genetika metabolismus MeSH
- infekce DNA virem * MeSH
- lidé MeSH
- Polyomavirus * genetika MeSH
- přirozená imunita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- DNA virů MeSH
BK polyomavirus (BKPyV) persists lifelong in renal and urothelial cells with asymptomatic urinary shedding in healthy individuals. In some immunocompromised persons after transplantation of hematopoietic stem cells (HSCT), the BKPyV high-rate replication is associated with haemorrhagic cystitis (HC). We tested whether the status of BKPyV immunity prior to HSCT could provide evidence for the BKPyV tendency to reactivate. We have shown that measurement of pretransplant anti-BKPyV 1 and 4 IgG levels can be used to evaluate the HC risk. Patients with anti-BKPyV IgG in the range of the 1st-2nd quartile of positive values and with positive clinical risk markers have a significantly increased HC risk, in comparison to the reference group of patients with "non-reactive" anti-BKPyV IgG levels and with low clinical risk (LCR) (p = 0.0009). The predictive value of pretransplant BKPyV-specific IgG was confirmed by determination of genotypes of the shed virus. A positive predictive value was also found for pretransplant T-cell immunity to the BKPyV antigen VP1 because the magnitude of IFN-γ T-cell response inversely correlated with posttransplant DNAuria and with HC. Our novel data suggest that specific T-cells control BKPyV latency before HSCT, and in this way may influence BKPyV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of HSCT recipients at high risk of BKPyV disease.
