HSV-1 Dotaz Zobrazit nápovědu
Devítiměsíční dítě bylo přijato k hospitalizaci na Kliniku dětí a dorostu FNKV pro impetiginizovanou blefaritidu pravého oka. Z tekutiny jedné z eflorescencí byla v naší laboratoři izolována NK a vyšetřena metodou real time PCR pomocí detekčního kitu HSV1/2 (Roche). Rozlišení mezi typy HSV I a 2 se v tomto testu provádí na základě odlišné teploty tání amplifikované dvouvláknové NK (hodnota Tm), která je pro HSV-l 54 °C ± 2,5 °C a pro HSV-2 66,5 °C ± 2,5 °C. Amplifikovaný vzorek NK se vyznačoval atypickou hodnotouTm, která byla 59 °C. Proto jsme izolovanou NK vyšetřili ještě další metodou, nested PCK Touto druhou PCR byla potvrzena přítomnost HSV-l NK. Přestože amplifikovaná NK vykazovala atypickou hodnotu Tm, onemocnění dobře reagovalo na Acyklovir a po nasazení Herpesinu (i.v. po dobu 5 dnů) se infekce víček oka zcela zhojila.
A 9-month-old boy with impetigious blepharitis of the right eye was admitted to the Department of children and adolescents of the Královske Vinohrady University Hospital. NA isolated from lesion fluid was screened using real-time PCR based HSV 1/2 detection kit (Roche). Differentiation between HSV types 1 and 2 in this assay is based on variation of double-stranded DNA melting temperature (Tm), being 54 °C + 2,5 °C for HSV-l and 66,5 °C ± 2, 2,5 °C for HSV-2. Since the amplified NA from the sample showed an atypical Tm of 59 °C, nested PCR was used for futher analysis: the presence of HSV-l NA was confirmed by the latter. In spite of the atypical Tm value, the eyelid infection was responsive to acyclovir and resolved after intravenous Herpesin given for 5 days.
- MeSH
- blefaritida diagnóza etiologie farmakoterapie MeSH
- dítě MeSH
- elektroforéza v agarovém gelu MeSH
- lidé MeSH
- lidský herpesvirus 1 genetika MeSH
- mutace MeSH
- polymerázová řetězová reakce metody MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Infekce způsobené herpetickými viry jsou jednou z nejčastějších virových komplikací u imunokompromitovaných nemocných, obzvláště pacientů s hematoonkologickými onemocněními. Mnoho víme o infekcích způsobených HSV-1 a HSV-2 a máme dobře popsané algoritmy profylaxe. Naopak u reaktivací či nemocí způsobených HHV-6 a HHV-8 nám stále chybí jednoznačná příčinná korelace a význam těchto virů u hematoonkologických nemocných není zcela jasný.
HSV-1, HSV-2, HHV-6, HHV-8, in haematooncological patients Herpesvirus infections are the main cause of viral complications in immunocompromised patients, especially in patients with haematooncological malignancies. HSV-1 and HSV-2 are well known pathogens in these types of patients. There is a good algorithm for prevention and treatment of these viral infections. On the other hand, we do not have good correlation between HHV-6 and HHV-8 reactivation and disease in haematooncological patients.
- MeSH
- antivirové látky * aplikace a dávkování škodlivé účinky MeSH
- chemoprofylaxe * metody MeSH
- hematologické nádory imunologie komplikace MeSH
- herpetické infekce * epidemiologie farmakoterapie krev prevence a kontrola MeSH
- hostitel s imunodeficiencí * imunologie účinky léků MeSH
- kvantitativní polymerázová řetězová reakce metody MeSH
- lidé MeSH
- lidský herpesvirus 1 imunologie izolace a purifikace patogenita účinky léků MeSH
- lidský herpesvirus 2 imunologie izolace a purifikace patogenita účinky léků MeSH
- lidský herpesvirus 6 imunologie izolace a purifikace patogenita účinky léků MeSH
- lidský herpesvirus 8 imunologie izolace a purifikace patogenita účinky léků MeSH
- transplantace hematopoetických kmenových buněk metody škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- MeSH
- cyklofosfamid MeSH
- herpes simplex MeSH
- hydrokortison MeSH
- imunizace MeSH
- imunosupresivní léčba MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
Psoromic acid (PA), a bioactive lichen-derived compound, was investigated for its inhibitory properties against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), along with the inhibitory effect on HSV-1 DNA polymerase, which is a key enzyme that plays an essential role in HSV-1 replication cycle. PA was found to notably inhibit HSV-1 replication (50% inhibitory concentration (IC50): 1.9 μM; selectivity index (SI): 163.2) compared with the standard drug acyclovir (ACV) (IC50: 2.6 μM; SI: 119.2). The combination of PA with ACV has led to potent inhibitory activity against HSV-1 replication (IC50: 1.1 µM; SI: 281.8) compared with that of ACV. Moreover, PA displayed equivalent inhibitory action against HSV-2 replication (50% effective concentration (EC50): 2.7 μM; SI: 114.8) compared with that of ACV (EC50: 2.8 μM; SI: 110.7). The inhibition potency of PA in combination with ACV against HSV-2 replication was also detected (EC50: 1.8 µM; SI: 172.2). Further, PA was observed to effectively inhibit HSV-1 DNA polymerase (as a non-nucleoside inhibitor) with respect to dTTP incorporation in a competitive inhibition mode (half maximal inhibitory concentration (IC50): 0.7 μM; inhibition constant (Ki): 0.3 μM) compared with reference drugs aphidicolin (IC50: 0.8 μM; Ki: 0.4 μM) and ACV triphosphate (ACV-TP) (IC50: 0.9 μM; Ki: 0.5 μM). It is noteworthy that the mechanism by which PA-induced anti-HSV-1 activity was related to its inhibitory action against HSV-1 DNA polymerase. Furthermore, the outcomes of in vitro experiments were authenticated using molecular docking analyses, as the molecular interactions of PA with the active sites of HSV-1 DNA polymerase and HSV-2 protease (an essential enzyme required for HSV-2 replication) were revealed. Since this is a first report on the above-mentioned properties, we can conclude that PA might be a future drug for the treatment of HSV infections as well as a promising lead molecule for further anti-HSV drug design.
- MeSH
- antivirové látky * chemie farmakologie MeSH
- benzoxepiny * chemie farmakologie MeSH
- Cercopithecus aethiops MeSH
- DNA-dependentní DNA-polymerasy * chemie metabolismus MeSH
- inhibitory syntézy nukleových kyselin chemie farmakologie MeSH
- kyseliny karboxylové * chemie farmakologie MeSH
- lidé MeSH
- lidský herpesvirus 1 fyziologie MeSH
- lidský herpesvirus 2 fyziologie MeSH
- lišejníky chemie MeSH
- replikace viru účinky léků MeSH
- simulace molekulového dockingu * MeSH
- Vero buňky MeSH
- virové proteiny * antagonisté a inhibitory chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Balb/c mice were immunized with the recombinant fusion protein gD1/313 (FpgD1/313 representing the ectodomain of HSV-1 gD), with the non-pathogenic ANGpath gE-del virus, with the plasmid pcDNA3.1-gD expressing full-length gD1 and with the recombinant immediate early (IE) HSV-1 protein ICP27. Specific antibodies against these antigens (as detected by ELISA) reached high titers with the exception of the DNA vaccine. High-grade protection against challenge with the virulent strain SC16 was found following immunization with the pcDNA3.1-gD plasmid and with the gE-del virus. Medium grade, but satisfactory protection developed after immunization with the FpgD1/313 and minimum grade protection was seen upon immunization with the IE/ICP27 polypeptide. A considerable response of peripheral blood cells (PBL) and splenocytes in the lymphocyte transformation test (LTT) was found in mice immunized with FpgD1/313, with the pcDNA3.1-gD plasmid and with the live ANGpathgE-del virus. For lymphocyte stimulation in vitro, the FpgD1/313 antigen was less effective than the purified gD1/313 polypeptide (cleaved off from the fusion protein); both proteins elicited higher proliferation at the 5 mug per 0.1 mL dose than at the 1 mug per 0.1 mL dose. The secretion of Th type 1 (TNF, IFN-gamma and IL-2) and Th type 2 (IL-4 and IL-6) cytokines was tested in the medium fluid of purified PBL and splenocyte cultures; their absolute values were expressed in relative indexes. The PBL from FpgD1/313 immunized mice showed increased secretion of both T(H)1 (TNF) as well as T(H)2 (IL-4) cytokines (7-10-fold, respectively). Splenocytes from FpgD1/313 immunized mice showed a significant (23-fold) increase in IL-4 production.
- MeSH
- aktivace lymfocytů MeSH
- buněčné linie MeSH
- cytokiny biosyntéza imunologie MeSH
- imunizace MeSH
- krevní buňky imunologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- lidský herpesvirus 1 genetika imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- protilátky virové krev MeSH
- Simplexvirus imunologie MeSH
- T-lymfocyty imunologie MeSH
- vakcína proti viru herpes simplex aplikace a dávkování imunologie MeSH
- virové proteiny genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
