Vaccinia virus (VACV) is an enveloped DNA virus from the Orthopoxvirus family, various strains of which were used in the successful eradication campaign against smallpox. Both original and newer VACV-based replicating vaccines reveal a risk of serious complications in atopic individuals. VACV encodes various factors interfering with host immune responses at multiple levels. In atopic skin, the production of type I interferon is compromised, while VACV specifically inhibits the phosphorylation of the Interferon Regulatory Factor 3 (IRF-3) and expression of interferons. To overcome this block, we generated a recombinant VACV-expressing murine IRF-3 (WR-IRF3) and characterized its effects on virus growth, cytokine expression and apoptosis in tissue cultures and in spontaneously atopic Nc/Nga and control Balb/c mice. Further, we explored the induction of protective immune responses against a lethal dose of wild-type WR, the surrogate of smallpox. We demonstrate that the overexpression of IRF-3 by WR-IRF3 increases the expression of type I interferon, modulates the expression of several cytokines and induces superior protective immune responses against a lethal poxvirus challenge in both Nc/Nga and Balb/c mice. Additionally, the results may be informative for design of other virus-based vaccines or for therapy of different viral infections.
- MeSH
- exprese genu genetika MeSH
- imunita imunologie MeSH
- infekce vyvolané poxviry imunologie prevence a kontrola MeSH
- interferon typ I metabolismus MeSH
- interferonový regulační faktor 3 genetika imunologie MeSH
- interleukin-1beta imunologie MeSH
- kůže imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- Poxviridae patogenita MeSH
- regulace exprese virových genů genetika MeSH
- replikace viru imunologie MeSH
- vakcínie virologie MeSH
- virové vakcíny imunologie MeSH
- virus vakcinie genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.
- MeSH
- adaptivní imunita genetika MeSH
- bronchy cytologie fyziologie MeSH
- cilie fyziologie MeSH
- COVID-19 genetika imunologie virologie MeSH
- genetická predispozice k nemoci MeSH
- interakce mikroorganismu a hostitele genetika imunologie MeSH
- koronavirové infekce genetika imunologie přenos virologie MeSH
- koronavirus MERS imunologie izolace a purifikace patogenita MeSH
- lidé MeSH
- objevující se infekční nemoci genetika imunologie přenos virologie MeSH
- přirozená imunita genetika MeSH
- protilátky virové MeSH
- replikace viru genetika imunologie MeSH
- respirační sliznice cytologie fyziologie MeSH
- SARS-CoV-2 imunologie patogenita MeSH
- velbloudi genetika imunologie virologie MeSH
- zdroje nemoci virologie MeSH
- zoonózy genetika imunologie přenos virologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Spojené arabské emiráty MeSH
Recent studies have shown a significant level of T cell immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in convalescent coronavirus disease 2019 (COVID-19) patients and unexposed healthy individuals. Also, SARS-CoV-2-reactive T memory cells occur in unexposed healthy individuals from endemic coronaviruses that cause the 'common cold.' The finding of the expression of adaptive SARS-CoV-2-reactive T memory cells in unexposed healthy individuals may be due to multiple cross-reactive viral protein targets following previous exposure to endemic human coronavirus infections. The opinion of the authors is that determination of protein sequence homologies across seemingly disparate viral protein libraries may provide epitope-matching data that link SARS-CoV-2-reactive T memory cell signatures to prior administration of cross-reacting vaccines to common viral pathogens. Exposure to SARS-CoV-2 initiates diverse cellular immune responses, including the associated 'cytokine storm'. Therefore, it is possible that the intact virus possesses a required degree of conformational matching, or stereoselectivity, to effectively target its receptor on multiple cell types. Therefore, conformational matching may be viewed as an evolving mechanism of viral infection and viral replication by an evolutionary modification of the angiotensin-converting enzyme 2 (ACE2) receptor required for SARS-CoV-2 binding and host cell entry. The authors propose that convalescent memory T cell immunity in individuals with mild or asymptomatic SARS-CoV-2 infection may result from an evolutionarily adapted immune response to coronavirus and the 'common cold'.
- MeSH
- angiotensin-konvertující enzym 2 genetika MeSH
- asymptomatické infekce * MeSH
- buněčná imunita genetika MeSH
- COVID-19 krev diagnóza imunologie virologie MeSH
- epitopy T-lymfocytární genetika imunologie MeSH
- imunogenicita vakcíny MeSH
- imunologická paměť genetika MeSH
- internalizace viru MeSH
- lidé MeSH
- molekulární evoluce MeSH
- nachlazení imunologie prevence a kontrola virologie MeSH
- protilátky virové MeSH
- replikace viru genetika imunologie MeSH
- Rhinovirus genetika imunologie MeSH
- SARS-CoV-2 imunologie patogenita MeSH
- sekvenční homologie MeSH
- stupeň závažnosti nemoci MeSH
- T-lymfocyty - podskupiny imunologie MeSH
- T-lymfocyty imunologie MeSH
- virové proteiny genetika imunologie MeSH
- virové vakcíny aplikace a dávkování imunologie MeSH
- zkřížené reakce genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- imunopatogeneze,
- MeSH
- Cytomegalovirus imunologie patogenita MeSH
- Herpesviridae imunologie klasifikace patogenita MeSH
- imunitní únik fyziologie imunologie MeSH
- lidé MeSH
- lidský herpesvirus 1 imunologie patogenita MeSH
- přirozená imunita MeSH
- replikace viru fyziologie imunologie MeSH
- virové nemoci imunologie patofyziologie MeSH
- virus Epsteinův-Barrové imunologie patogenita MeSH
- virus spalniček imunologie patogenita MeSH
- viry hepatitidy imunologie patogenita MeSH
- viry * imunologie klasifikace patogenita MeSH
- zánět * etiologie imunologie patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Klíčová slova
- imunopatogeneze,
- MeSH
- AIDS imunologie patofyziologie terapie MeSH
- HIV infekce * dějiny diagnóza epidemiologie imunologie patofyziologie terapie MeSH
- HIV-1 fyziologie genetika imunologie patogenita ultrastruktura MeSH
- koitus MeSH
- lidé MeSH
- replikace viru imunologie MeSH
- syndromy imunologické nedostatečnosti * dějiny imunologie patofyziologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- antivirové látky aplikace a dávkování klasifikace škodlivé účinky MeSH
- cytomegalovirové infekce * diagnóza etiologie farmakoterapie imunologie MeSH
- Cytomegalovirus imunologie patogenita ultrastruktura MeSH
- lidé MeSH
- replikace viru imunologie MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The relationship between Epstein-Barr virus (EBV) and the germinal centre (GC) of the asymptomatic host remains an enigma. The occasional appearance of EBV-positive germinal centres in some patients, particularly those with a history of immunosuppression, suggests that EBV numbers in the GC are subject to immune control. The relationship, if any, between lymphoid hyperplasia with EBV-positive germinal centres and subsequent or concurrent lymphomagenesis remains to be clarified. As far as the development of EBV-associated Hodgkin's lymphoma is concerned, the suppression of virus replication, mediated by LMP1 on the one hand, and the loss of B-cell receptor signalling on the other, appears to be an important pathogenic mechanism. A further important emerging concept is that alterations in the microenvironment of the EBV-infected B-cell may be important for lymphomagenesis.
- MeSH
- B-lymfocyty imunologie virologie MeSH
- buněčná diferenciace imunologie MeSH
- dospělí MeSH
- Hodgkinova nemoc imunologie virologie MeSH
- infekce virem Epsteina-Barrové virologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- proteiny virové matrix MeSH
- pseudolymfom virologie MeSH
- receptory antigenů B-buněk imunologie MeSH
- replikace viru imunologie MeSH
- virus Epsteinův-Barrové imunologie MeSH
- zárodečné centrum lymfatické uzliny imunologie virologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
We constructed recombinant vaccinia viruses (VACVs) coexpressing the insulin-like growth factor-binding protein-3 (IGFBP-3) gene and the fusion gene encoding the SigE7Lamp antigen. The expression of the IGFBP-3 transgene was regulated either by the early H5 promoter or by the synthetic early/late (E/L) promoter. We have shown that IGFBP-3 expression regulated by the H5 promoter yielded higher amount of IGFBP-3 protein when compared with the E/L promoter. The immunization with P13-SigE7Lamp-H5-IGFBP-3 virus was more effective in inhibiting the growth of TC-1 tumors in mice and elicited higher T-cell response against VACV-encoded antigen than the P13-SigE7Lamp-TK(-) control virus. We found that high-level production of IGFBP-3 enhanced virus replication both in vitro and in vivo, resulting in more profound antigen stimulation. Production of IGFBP-3 was associated with a higher adsorption rate of P13-SigE7Lamp-H5-IGFBP-3 to CV-1 cells when compared with P13-SigE7Lamp-TK(-). Intracellular mature virions (IMVs) of the IGFBP-3-expressing virus P13-SigE7Lamp-H5-IGFBP-3 have two structural differences: they incorporate the IGFBP-3 protein and they have elevated phosphatidylserine (PS) exposure on outer membrane that could result in increased uptake of IMVs by macropinocytosis. The IMV PS content was measured by flow cytometry using microbeads covered with immobilized purified VACV virions.
- MeSH
- antigeny virové imunologie MeSH
- IGFBP-3 genetika imunologie MeSH
- imunizace metody MeSH
- lidský papilomavirus 16 genetika imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- Papillomavirus E7 - proteiny genetika imunologie MeSH
- promotorové oblasti (genetika) MeSH
- replikace viru imunologie MeSH
- T-lymfocyty imunologie MeSH
- tvorba protilátek MeSH
- vakcinace metody MeSH
- virové vakcíny imunologie farmakologie MeSH
- virus vakcinie genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Práce se zabývá virovými hepatitidami typu A–E z pohledu posudkového lékaře s klinickou praxí infekcionisty. Uvádí epidemiologická, klinická a diferenciálně diagnostická hlediska i jejich dopad na práci posudkového lékaře, zejména při posuzování pracovní neschopnosti (PN) a invalidity.
The paper deals with types A-E viral hepatitis from the perspective of the physician reviewer with the clinical practice of an infectionist. It presents epidemiological, clinical and differential diagnostic aspects and their impact on the work of the physician reviewer, especially at assessing working disability and invalidity.
- MeSH
- biologické markery krev moč MeSH
- chronická hepatitida diagnóza klasifikace terapie MeSH
- diagnostické techniky a postupy využití MeSH
- hepatocelulární karcinom diagnóza terapie MeSH
- klinický obraz nemoci MeSH
- lidé MeSH
- posuzování zdravotní způsobilosti MeSH
- pracovní neschopnost MeSH
- replikace viru genetika imunologie účinky léků MeSH
- sérum imunologie účinky léků MeSH
- virová hepatitida u lidí diagnóza klasifikace terapie MeSH
- Check Tag
- lidé MeSH