scholarly journals A method for evaluating antiviral drug susceptibility of Epstein-Barr virus

2010 ◽  
pp. 1 ◽  
Author(s):  
Hank Henry H Balfour, Jr

2014 ◽  
Vol 63 (4) ◽  
pp. 34-38 ◽  
Author(s):  
Vera Aleksandrovna Kolmyk ◽  
Ruslan Abdullayevich Nasyrov ◽  
Galiya Fettyakhovna Kutusheva

20 female patients aged 18-40 years old with a complicated anamnesis have been examined. Besides the regular clinical analysis the Pipel-byopsy was carried out with the immunohistochemical and histological investigation of the material. The expression level of estrogen and progesterone receptors has been determined. As well as the antigens of HSV, CMV and Epstein-Barr virus. In the case when chronic endometritis was diagnosed with the appearance of any of the viruses, the immunomodulating and antiviral therapy was administered. In the treatment of chronic endometritis associated with herpes simplex virus is advisable to administer an antiviral drug cour at least 3 months.



2020 ◽  
Vol 295 (21) ◽  
pp. 7431-7441 ◽  
Author(s):  
Qian Wang ◽  
Nannan Zhu ◽  
Jiayuan Hu ◽  
Yan Wang ◽  
Jun Xu ◽  
...  

Lytic replication of Epstein-Barr virus (EBV) is not only essential for its cell–to–cell spread and host–to–host transmission, but it also contributes to EBV-induced oncogenesis. Thus, blocking EBV lytic replication could be a strategy for managing EBV-associated diseases. Previously, we identified a series of natural lignans isolated from the roots of Saururus chinensis (Asian lizard's tail) that efficiently block EBV lytic replication and virion production with low cytotoxicity. In this study, we attempted to elucidate the molecular mechanism by which these lignans inhibit EBV lytic replication. We found that a representative compound, CSC27 (manassantin B), inhibits EBV lytic replication by suppressing the expression of EBV immediate-early gene BZLF1 via disruption of AP-1 signal transduction. Further analysis revealed that manassantin B specifically blocks the mammalian target of rapamycin complex 2 (mTORC2)-mediated phosphorylation of AKT Ser/Thr protein kinase at Ser-473 and protein kinase Cα (PKCα) at Ser-657. Using phosphoinositide 3-kinase–AKT-specific inhibitors for kinase mapping and shRNA-mediated gene silencing, we validated that manassantin B abrogates EBV lytic replication by inhibiting mTORC2 activity and thereby blocking the mTORC2–PKC/AKT-signaling pathway. These results suggest that mTORC2 may have utility as an antiviral drug target against EBV infections and also reveal that manassantin B has potential therapeutic value for managing cancers that depend on mTORC2 signaling for survival.



2019 ◽  
Vol 6 (1) ◽  
pp. 19-26
Author(s):  
Irina A. Rakityanskaya ◽  
T. S Ryabova ◽  
U. A Todzhibaev ◽  
A. A Kalashnikova

Introduction. Epstein-Barr virus (EBV) causes recurrent infectious mononucleosis-like symptoms. Today poisons of insects and animals were shown to be rich sources of antimicrobial substances (peptides) and contain a wide range of active biological compounds. Antimicrobial peptides play an important role in the immune response of the host’s innate immunity to pathogenic microorganisms. Based on antimicrobial peptides in Russia, an antiviral drug allokin-alpha has been developed. The active ingredient of the drug is cytokine-like peptide alloferon. The purpose of the study is to evaluate the effect of allokin-alpha therapy on the amount of EBV DNA in saliva samples and clinical complaints in patients with chronic Epstein-Barr viral infection (EBI). Material and methods. 59 chronic EBI patients (45 women and 14 men; mean age 32.52 ± 1.75 years) were examined. Patients were subjected to quantitative determination of Epstein-Barr virus DNA in saliva samples by the method of polymerase chain reaction (PCR) with real-time hybridization-fluorescence detection. The analytical sensitivity of the test system is 400 copies/ml. The patients were divided into two groups: 26 patients who received allokin-alpha therapy (9 injections subcutaneously with 1.0 mg every other day) were included in the 1st group; the 2nd group included 33 patients who received Valtrex (500 mg 2 times/day, orally) for 2 months. Results. After treatment with allocin-alpha, negative results of PCR were obtained in 59.67% of patients. After two months of Valtrex therapy, negative PCR results were obtained in only 27.27% of patients. The correlation analysis revealed a significant effect of the initial number of copies of EBV DNA on the severity of clinical complaints in the general group of EBV patients. Discussion. Allokin-alpha improves the recognition of virus-infected cells and helps to suppress viral replication. Conclusion. Allokin-alpha therapy can be recommended for the treatment of chronic EBV infection in a dose of 1 mg subcutaneously every other day with a course dose of at least 9 injections.



Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 997 ◽  
Author(s):  
Graciela Andrei ◽  
Erika Trompet ◽  
Robert Snoeck

Epstein–Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35–50% of the cases when infection occurs later in life. EBV infects mainly B-cells and epithelial cells, establishing latency in resting memory B-cells and possibly also in epithelial cells. EBV is recognized as an oncogenic virus but in immunocompetent hosts, EBV reactivation is controlled by the immune response preventing transformation in vivo. Under immunosuppression, regardless of the cause, the immune system can lose control of EBV replication, which may result in the appearance of neoplasms. The primary malignancies related to EBV are B-cell lymphomas and nasopharyngeal carcinoma, which reflects the primary cell targets of viral infection in vivo. Although a number of antivirals were proven to inhibit EBV replication in vitro, they had limited success in the clinic and to date no antiviral drug has been approved for the treatment of EBV infections. We review here the antiviral drugs that have been evaluated in the clinic to treat EBV infections and discuss novel molecules with anti-EBV activity under investigation as well as new strategies to treat EBV-related diseases.



2018 ◽  
Vol 51 (4) ◽  
pp. 1500-1517 ◽  
Author(s):  
Meili Li ◽  
Tao Chen ◽  
Xingmei Zou ◽  
Zuo Xu ◽  
Yuanfang Wang ◽  
...  

Background/Aims: Epstein-Barr virus (EBV) BFLF2, the homologue of herpes simplex virus 1 (HSV-1) UL31, is crucial for the efficient viral DNA packaging and primary egress across the nuclear membrane. However, we still do not know its subcellular transport mechanisms. Methods: Interspecies heterokaryon assays were utilized to detect the nucleocytoplasmic shuttling of BFLF2, and mutation analysis, plasmid transfection and fluorescence microscopy assays were performed to identify the functional nuclear localization sequence (NLS) and nuclear export sequence (NES) of BFLF2 in live cells. Furthermore, the nuclear import and export of BFLF2 were assessed by confocal microscopy, co-immunoprecipitation and immunoblot assays. Results: BFLF2 was confirmed to shuttle between the nucleus and cytoplasm. Two predicted NESs were shown to be nonfunctional, yet we proved that the nuclear export of BFLF2 was mediated through transporter associated with antigen processing (TAP), but not chromosomal region maintenance 1 (CRM1) dependent pathway. Furthermore, one functional NLS, 22RRLMHPHHRNYTASKASAH40, was identified, and the aa22-23, aa22-25, aa28-30 and aa37-40 had an important role in the nuclear localization of BFLF2. Besides, the nuclear import of BFLF2 was demonstrated through Ran-, importin α7-, importin β1- and transportin-1-dependent mechanism that does not require importin α1, α3 and α5. Conclusion: These works are of significance for the further study of the functions of BFLF2 during EBV infection, as well as for further insights into the design of new antiviral drug target and vaccine development against EBV.



2019 ◽  
Vol 64 (3) ◽  
pp. 118-124
Author(s):  
I. A. Rakitianskaya ◽  
T. S. Riabova ◽  
U. A. Todzhibaev ◽  
A. A. Kalashnikova

Introduction. Epstein-Barr virus causes recurrent infectious mononucleosis-like symptoms. Today it is shown that the poisons of insects and animals are rich sources of antimicrobial substances (peptides) and contain a wide range of active biological compounds. Antimicrobial peptides play an important role in the immune response of the innate immunity of the host in the presence of pathogenic microorganisms. Russia has developed an antiviral drug Allokin-alpha on the basis of antimicrobial peptides. The active ingredient of this drug is cytokin-like peptide alloferon. The aim of the study is to evaluate the effect of allokin-alpha therapy on the amount of EBV DNA in saliva samples and clinical complaints in patients with chronic Epstein-Barr infection (ChEBVI). Material and methods. 59 patients with ChEBVI were examined (45 women and 14 men; mean age 32.52 ± 1.75 years). Patients were examined quantification of DNA Epstein-Barr virus in saliva samples by the method of polymerase chain reaction (PCR) with hybridization-fluorescence detection in “real time” mode. The analytical sensitivity of the test system is 400 copies / ml. Patients were randomized into two groups: group 1 (25 patients) received Allokin-alpha therapy (9 injections of s / c, 1.0 mg every other day); group 2 (33 patients) received Valtrex (500 mg x 2 times / day, by mouth) for two months. Results. 59.67% of patients had negative PCR results after treatment with Allocin-alpha. Only 27.27% of patients had negative PCR results after two months of treatment with Valtrex. In a correlation analysis, a significant effect of the initial number of copies of DNA EBV on the severity of clinical complaints in patients was revealed in the general group ChEBVI. Discussion. Allokin-alpha improves the recognition of virus-infected cells and helps suppress viral replication. Conclusions. Allocin-alpha therapy can be recommended for the treatment of chronic EBVI at a dose of 1 mg subcutaneously every other day with a course dose of at least 9 injections.



2007 ◽  
Vol 143 (1) ◽  
pp. 38-44 ◽  
Author(s):  
Mirvat Ballout ◽  
Raphaële Germi ◽  
Samira Fafi-Kremer ◽  
Josette Guimet ◽  
Gerard Barguès ◽  
...  


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