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

Romain, Charlotte A; Balfour, Henry H.; Vezina, Heather; Holman, Carol J.

doi:10.2147/vaat.s8575

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…It should be mentioned that no drug-associated mutations were identified in viral TK, PK, and/or DNA polymerase under pressure from GCV after 21 passages in cell culture for HVS and 45 passages for MHV-68. The ACV r HVS double mutant acquired an insertion of thymidine in the substrate binding site of the viral PK, at a position homologous to those of mutations mapped in HCMV pUL97 conferring GCV resistance (27,31). The HVS mutant was resistant to ACV and GCV; however, since it acquired another mutation in the viral DNA polymerase, we could not assess the impact of the PK mutation alone on the activation of ACV and GCV.…”

Section: Figmentioning

confidence: 99%

“…In contrast, no drug-resistant EBV and KSHV strains have ever been isolated from patients, though monitoring the development of resistance might be useful, especially when immunocompromised hosts with EBV or KSHV diseases are treated with antiviral agents (31). In addition, no studies have reported the in vitro selection and characterization of drug-resistant EBV and KSHV strains, while this has been extensively investigated for other herpesviruses, such as HSV, VZV, and HCMV.…”

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confidence: 99%

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Spectrum of Activity and Mechanisms of Resistance of Various Nucleoside Derivatives against Gammaherpesviruses

Coen

Duraffour

Topalis

et al. 2014

Antimicrob Agents Chemother

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The susceptibilities of gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and animal rhadinoviruses, to various nucleoside analogs was investigated in this work. Besides examining the antiviral activities and modes of action of antivirals currently marketed for the treatment of alpha-and/or betaherpesvirus infections (including acyclovir, ganciclovir, penciclovir, foscarnet, and brivudin), we also investigated the structure-activity relationship of various 5-substituted uridine and cytidine molecules. The antiviral efficacy of nucleoside derivatives bearing substitutions at the 5 position was decreased if the bromovinyl was replaced by chlorovinyl. 1-␤-D-Arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BVaraU), a nucleoside with an arabinose configuration of the sugar ring, exhibited no inhibitory effect against rhadinoviruses but was active against EBV. On the other hand, the fluoroarabinose cytidine analog 2=-fluoro-5-iodo-aracytosine (FIAC) showed high selectivity indices against gammaherpesviruses that were comparable to those of brivudin. Additionally, we selected brivudin-and acyclovir-resistant rhadinoviruses in vitro and characterized them by phenotypic and genotypic (i.e., sequencing of the viral thymidine kinase, protein kinase, and DNA polymerase) analysis. Here, we reveal key amino acids in these enzymes that play an important role in substrate recognition. Our data on drug susceptibility profiles of the different animal gammaherpesvirus mutants highlighted cross-resistance patterns and indicated that pyrimidine nucleoside derivatives are phosphorylated by the viral thymidine kinase and purine nucleosides are preferentially activated by the gammaherpesvirus protein kinase.T he gammaherpesvirus subfamily includes two major genera, the lymphocryptovirus and rhadinovirus, of which the human tumor viruses Epstein-Barr virus (EBV) and Kaposi's sarcomaassociated herpesvirus (KSHV), respectively, are the best-characterized members (1). A hallmark of these human herpesviruses is that they do not easily replicate in primary infection in cells in culture (2). In contrast, other members of the rhadinovirus genus, murine gammaherpesvirus 68 (MHV-68), herpesvirus saimiri (HVS), and rhesus rhadinovirus (RRV), are able to replicate to high titers in cell culture, and thus, they may serve as model systems for human gammaherpesviruses in experimental settings (3).Overall, antiherpesvirus therapies are aimed at selectively inhibiting the lytic replication of the virus. At present, the antiviral agents used in EBV and KSHV viral infections are those that are approved for the treatment of other herpesvirus infections (4), in particular ganciclovir (GCV) for both EBV and KSHV and also acyclovir (ACV) in the case of EBV. Other structurally related antiherpetics that are currently marketed, such as penciclovir (PCV) and brivudin (BVDU), have also been evaluated in vitro against EBV and KSHV replication (5-8) but have not been used in the clinic. Differences in antiviral act...

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Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

Spectrum of Activity and Mechanisms of Resistance of Various Nucleoside Derivatives against Gammaherpesviruses

Coen

Duraffour

Topalis

et al. 2014

Antimicrob Agents Chemother

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“…In this test, a cell suspension is simply mixed with dye and then visually examined to determine whether cells take up or exclude dye. The trypan blue exclusion test was used as previously described [17].…”

Section: Methodsmentioning

confidence: 99%

Antiviral and apoptosis modulating potential of fluorinated derivatives of uracil

Naumenko

Golovan

Zelena

et al. 2018

ScienceRise: Biological Science

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“…Several nucleoside analogs have in vitro activity against EBV, but a clinical benefit has not yet been proven for any of them. [4] Inflammatory side effects including airway obstruction or autoimmune conditions like anaemia and thrombocytopenia are frequently treated with corticosteroids, although their efficacy is debatable and they may hamper virus clearance. [3] Although the mechanism is unknown, primary EBV infection-related hepatitis is typically mild and self-limited.…”

Section: Introductionmentioning

confidence: 99%

Infectious Mononucleosis: A Case Report with Unusual Features and EBV Induced Hepatitis

Suresh,

Dharman

2023

Int J Res Rev

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Despite the fact that Epstein-Barr virus (EBV) infections are common, we continue to hear about new cases of the illness with bizarre and unique symptoms, which prompts the issue of how well we understand this disease. In developing countries, the average age at which an infection is contracted is rising. Other physical symptoms are less noticeable and liver involvement is more noticeable throughout these stages. To inform healthcare professionals of this change, an update on infectious mononucleosis (IM) variable manifestation is necessary. Although our patient didn't have many physical symptoms, blood testing revealed a typical picture of EBV-induced hepatitis. This instance is consistent with recent research suggesting that hepatic involvement is among the most noticeable symptoms in adults with primary EBV infection. Keywords: [Epstein-Barr virus, Infectious mononucleosis, Hepatitis]

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

Cited by 5 publications

References 24 publications

Spectrum of Activity and Mechanisms of Resistance of Various Nucleoside Derivatives against Gammaherpesviruses

Spectrum of Activity and Mechanisms of Resistance of Various Nucleoside Derivatives against Gammaherpesviruses

Antiviral and apoptosis modulating potential of fluorinated derivatives of uracil

Infectious Mononucleosis: A Case Report with Unusual Features and EBV Induced Hepatitis

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