poxvirus
Dotaz
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- MeSH
- DNA virů biosyntéza MeSH
- kuřecí embryo MeSH
- replikace viru MeSH
- virus vakcinie MeSH
- Check Tag
- kuřecí embryo MeSH
- MeSH
- infekce vyvolané poxviry MeSH
- Poxviridae izolace a purifikace patogenita MeSH
- Geografické názvy
- střední Afrika MeSH
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
- MeSH
- barvení a značení MeSH
- buněčné inkluze virové MeSH
- časové faktory MeSH
- cytoplazma mikrobiologie MeSH
- elektronová mikroskopie MeSH
- fluorescenční protilátková technika MeSH
- králíci MeSH
- kultivované buňky MeSH
- makrofágy mikrobiologie MeSH
- plicní alveoly MeSH
- počet buněk MeSH
- replikace viru MeSH
- virus vakcinie růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
9-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPDAP) and its cyclic form were selected for further evaluation as potential drug candidates against poxvirus infections. To increase bioavailability of these compounds, synthesis of their structurally diverse ester prodrugs was carried out: alkoxyalkyl (hexadecyloxypropyl, octadecyloxyethyl, hexadecyloxyethyl), pivaloyloxymethyl (POM), 2,2,2-trifluoroethyl, butylsalicylyl, and prodrugs based on peptidomimetics. Most HPMPDAP prodrugs were synthesized in the form of monoesters as well as the corresponding cyclic phosphonate esters. The activity was evaluated not only against vaccinia virus but also against different herpes viruses. The most potent and active prodrugs against vaccinia virus were the alkoxyalkyl ester derivatives of HPMPDAP, with 50% effective concentrations 400-600-fold lower than those of the parent compound. Prodrugs based on peptidomimetics, the 2,2,2-trifluoroethyl, the POM, and the butylsalicylyl derivatives, were able to inhibit vaccinia virus replication at 50% effective concentrations that were equivalent or ∼10-fold lower than those observed for the parent compounds.
- MeSH
- adenin analogy a deriváty chemická syntéza chemie farmakologie MeSH
- antivirové látky chemická syntéza chemie farmakologie MeSH
- estery MeSH
- Herpesviridae účinky léků MeSH
- kultivované buňky MeSH
- lidé MeSH
- organofosforové sloučeniny chemická syntéza chemie farmakologie MeSH
- Poxviridae účinky léků MeSH
- prekurzory léčiv chemická syntéza chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- RNA-viry účinky léků MeSH
- stereoizomerie MeSH
- virologie metody MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- biologická kontrola škůdců MeSH
- entomologie MeSH
- lesnictví MeSH
- stromy parazitologie MeSH
- Geografické názvy
- Česká republika MeSH
