HSV-1 Dotaz Zobrazit nápovědu
A 9-month-old boy with impetigious blepharitis of the right eye was admitted to the Department of children and adolescents of the Kralovske 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 degrees C +/- 2,5 degrees C for HSV-1 and 66,5 degrees C +/- 2,5 degrees C for HSV-2. Since the amplified NA from the sample showed an atypical Tm of 59 degrees C, nested PCR was used for futher analysis: the presence of HSV-1 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
- herpes simplex diagnóza MeSH
- impetigo diagnóza virologie MeSH
- kojenec MeSH
- lidé MeSH
- lidský herpesvirus 1 genetika izolace a purifikace MeSH
- mutace MeSH
- obličejové dermatózy diagnóza virologie MeSH
- oční víčka MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky 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.
- Klíčová slova
- HSV, HSV replication, anti-enzymatic properties, antiherpetic, lichen metabolites, psoromic acid,
- 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
- Názvy látek
- antivirové látky * MeSH
- benzoxepiny * MeSH
- DNA-dependentní DNA-polymerasy * MeSH
- inhibitory syntézy nukleových kyselin MeSH
- kyseliny karboxylové * MeSH
- psoromic acid MeSH Prohlížeč
- virové proteiny * 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 microg per 0.1 mL dose than at the 1 microg 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
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- cytokiny MeSH
- protilátky virové MeSH
- vakcína proti viru herpes simplex MeSH
- virové proteiny MeSH
Serious burn trauma is associated with changes of the immune system, and immunosuppression induced by burn trauma can lead to reactivation of latent infections. Herpetic viruses are known for their lifelong persistence after primary infection and ability to reactivate. Their reactivation in the setting of burn trauma or primary infection can cause serious complications for a weakened burn patient. Presented is a case of a toddler who sustained second-degree scald burns over 20% of his body surface area. The injury was complicated by a multi-resistant bacterial infection in addition to reactivation of a latent HHV-6 infection concurrently with a primary HSV-1 infection. Described further are basic diagnostics, local and systemic treatment strategies, and other complications due to disseminated herpetic infections. To date, HHV-6 reactivation has not been described in conjunction with burn injury.
- Klíčová slova
- HHV-6, HSV-1, Pediatric burn trauma, herpes virus infection,
- MeSH
- aktivace viru fyziologie MeSH
- bakteriální infekce etiologie mikrobiologie MeSH
- herpetické infekce etiologie virologie MeSH
- lidé MeSH
- lidský herpesvirus 1 izolace a purifikace MeSH
- lidský herpesvirus 6 izolace a purifikace MeSH
- mnohočetná bakteriální léková rezistence fyziologie MeSH
- popálení komplikace patofyziologie MeSH
- předškolní dítě MeSH
- Check Tag
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
While few studies have revealed the biological properties of brassicasterol, a phytosterol, against some biological and molecular targets, it is believed that there are still many activities yet to be studied. In this work, brassicasterol exerts a therapeutic utility in an in vitro setting against herpes simplex virus type 1 (HSV-1) and Mycobacterium tuberculosis (Mtb) as well as a considerable inhibitory property against human angiotensin-converting enzyme (ACE) that plays a dynamic role in regulating blood pressure. The antireplicative effect of brassicasterol against HSV-1 is remarkably detected (50% inhibitory concentration (IC50): 1.2 µM; selectivity index (SI): 41.7), while the potency of its effect is ameliorated through the combination with standard acyclovir with proper SI (IC50: 0.7 µM; SI: 71.4). Moreover, the capacity of this compound to induce an adequate level of antituberculosis activity against all Mtb strains examined (minimum inhibitory concentration values ranging from 1.9 to 2.4 µM) is revealed. The anti-ACE effect (12.3 µg/mL; 91.2% inhibition) is also ascertained. Molecular docking analyses propose that the mechanisms by which brassicasterol induces anti-HSV-1 and anti-Mtb might be related to inhibiting vital enzymes involved in HSV-1 replication and Mtb cell wall biosynthesis. In summary, the obtained results suggest that brassicasterol might be promising for future anti-HSV-1, antituberculosis, and anti-ACE drug design.
- Klíčová slova
- ACE, HSV, HSV-1 DNA polymerase, HSV-1 TK, Mycobacterium tuberculosis, UDP-galactopyranose mutase, brassicasterol, human CDK2, phytosterols,
- Publikační typ
- časopisecké články MeSH
The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1, responsible for oral herpes, and HSV-2, primarily causing genital herpes. Both types can lead to significant complications, including neurological issues. Conventional treatment, involving acyclovir and its derivatives, faces challenges due to drug resistance. This underscores the imperative for continual research and development of new drugs, with a particular emphasis on exploring the potential of natural antivirals. Flavonoids have demonstrated promise in combating various viruses, including those within the herpesvirus family. This review, delving into recent studies, reveals the intricate mechanisms by which flavonoids decode their antiviral capabilities against HSV. By disrupting key stages of the viral life cycle, such as attachment to host cells, entry, DNA replication, latency, and reactivation, flavonoids emerge as formidable contenders in the ongoing battle against HSV infections.
- Klíčová slova
- HSV life cycle, HSV-1, HSV-2, antiviral properties, cellular pathways, drug resistance, flavonoids, herpes simplex virus, host–virus interaction, natural antivirals, natural products,
- MeSH
- antivirové látky farmakologie terapeutické užití MeSH
- flavonoidy farmakologie terapeutické užití MeSH
- herpes simplex * farmakoterapie MeSH
- lidé MeSH
- lidský herpesvirus 1 * fyziologie MeSH
- stadia vývoje MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antivirové látky MeSH
- flavonoidy MeSH
Diphosphates of N-(S)-(3-hydroxy-2-phosphonylmethoxypropyl) and N-(2-phosphonylmethoxyethyl) derivatives of purine and pyrimidine heterocyclic bases inhibit HSV-1 encoded ribonucleotide reductase. Of the compounds studied, the most efficient inhibitors of CDP reduction (at 5.1 mumols.l-1) by the HSV-1-encoded enzyme are HPMPApp (IC50 = 0.9 mumols.l-1) and PMEApp (IC50 = 8 mumol.l-1). PMEApp does not inhibit the enzyme isolated from the mutant HSV-1 KOS strain PMEAr which is resistant to PMEA at a concentration of 100 micrograms/ml. The enzyme isolated from the PMEA-resistant virus strain is also insensitive to inhibitory effects of hydroxyurea and HPMPApp. Thus, the inhibitory potency of HPMPApp and PMEApp toward HSV-1 encoded ribonucleotide reductase might be connected with the anti-HSV activity of HPMPA and PMEA.
- MeSH
- adenin aplikace a dávkování analogy a deriváty farmakologie MeSH
- antivirové látky farmakologie MeSH
- fosforylace MeSH
- kultivované buňky MeSH
- organofosfonáty * MeSH
- organofosforové sloučeniny aplikace a dávkování farmakologie MeSH
- ribonukleotidreduktasy antagonisté a inhibitory MeSH
- Simplexvirus účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine MeSH Prohlížeč
- adefovir MeSH Prohlížeč
- adenin MeSH
- antivirové látky MeSH
- organofosfonáty * MeSH
- organofosforové sloučeniny MeSH
- ribonukleotidreduktasy MeSH
The ability of two strains of herpes simplex virus type 1 (HSZP and KOS) to shut off the host protein synthesis in the presence of Actinomycin D was investigated. The HSZP strain proved to be defective with respect to the so-called early shutoff function. In superinfection experiments, the HSZP was effective at interfering with the early shutoff function of the KOS strain provided that the HSZP infection preceded KOS superinfection. Heat inactivation of the HSZP did not lead to the loss of its interfering ability. Evidence was given that this interference was neither due to the hindrance of the KOS by HSZP at adsorption nor due its exclusion during penetration.
- MeSH
- daktinomycin farmakologie MeSH
- replikace viru MeSH
- Simplexvirus růst a vývoj MeSH
- Vero buňky MeSH
- virové proteiny biosyntéza MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- daktinomycin MeSH
- virové proteiny MeSH
The authors present a case report of unrecognized herpes genitalis, which was caused by primary HSV-1 infection. The 28-year old female was examined by three board certified gynaecologist and initially treated as mycotic vulvitis. The authors point out the atypical course in the patient without anti-HSV-1 and HSV-2 antibodies. This infection is rather very painful, extensive and with complications. Thus, it is necessary to consider the diagnosis and to begin antiviral therapy as soon as possible.
Based on seroepidemiological studies, human herpes simplex virus types 1 and 2 (HSV-1, HSV-2) are put in relation with a number of cancer diseases; however, they do not appear to play a direct role, being only considered cofactors. Their ability to transform the cells in vitro could be demonstrated experimentally by removing their high lytic ability by a certain dose of UV radiation or by photoinactivation in the presence of photosensitizers, such as neutral red or methylene blue, or culturing under conditions suppressing their lytic activity. However, recent studies indicate that UV irradiated or photoinactivated HSV-1 and HSV-2, able to transform non-transformed cells, behave differently in transformed cells suppressing their transformed phenotype. Furthermore, both transforming and transformed phenotype suppressing activities are pertaining only to non-syncytial virus strains. There are some proposed mechanisms explaining their transforming activity. According to the "hit and run" mechanism, viral DNA induces only initiation of transformation by interacting with cellular DNA bringing about mutations and epigenetic changes and is no longer involved in other processes of neoplastic progression. According to the "hijacking" mechanism, virus products in infected cells may activate signalling pathways and thus induce uncontrolled proliferation. Such a product is e.g. a product of HSV-2 gene designated ICP10 that encodes an oncoprotein RR1PK that activates the Ras pathway. In two cases of cancer, in the case of serous ovarian carcinoma and in some prostate tumours, virus-encoded microRNAs (miRNAs) were detected as a possible cofactor in tumorigenesis. And, recently described herpes virus-associated growth factors with transforming and transformation repressing activity might be considered important factors playing a role in tumour formation. And finally, there is a number of evidence that HSV-2 may increase the risk of cervical cancer after infection with human papillomaviruses. A similar situation is with human cytomegalovirus; however, here, a novel mechanism named oncomodulation has been proposed. Oncomodulation means that HCMV infects tumour cells and modulates their malignant properties without having a direct effect on cell transformation.
- MeSH
- DNA virů genetika MeSH
- herpetické infekce komplikace virologie MeSH
- lidé MeSH
- lidský herpesvirus 1 genetika patogenita MeSH
- lidský herpesvirus 2 genetika patogenita MeSH
- nádory virologie MeSH
- virová transformace buněk genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- DNA virů MeSH
