HSV Susceptibility to Acyclovir – Genotypic and Phenotypic Characterization

Abstract

Background Infections due to drug-resistant herpes simplex viruses (HSV) represent an important clinical concern, especially in immunocompromised patients. The present study was aimed at detecting acyclovir (ACV) susceptibility in HSV clinical samples. Methods A total of 13 HSV-positive clinical samples (5 HSV-1 and 8 HSV-2) recovered from patients (1 immunocompromised and 12 of unknown immune status) were included in the study. The genotypic analysis involved an initial UL23 (thymidine kinase) gene sequencing, followed by a confirmatory phenotypic assay using plaque reduction technique. Results Two novel amino acid changes, A37V and H283N, were detected in HSV-1 positive clinical samples, which were found to be susceptible to acyclovir (half maximal effective concentration = 1.5 μM) by plaque reduction assay. Conclusions These two novel amino acid changes could be therefore considered as natural polymorphisms, a phenomenon widely associated with the HSV-UL23 gene.

Diagnóstico citopatológico de infecção pelo vírus herpes simples causando úlceras aftosas orais em paciente com leucemia linfocítica aguda

“…Resistance to acyclovir occurs due to mutations in the viral gene responsible for encoding the enzyme thymidine kinase (TK), which is essential for phosphorylation and the subsequent activation and inhibition of viral DNA synthesis in infected cells. 12 Foscarnet (phosphonoformic acid) and cidofovir are often used as treatments for herpetic lesions in patients with antiviral resistance. They function by acting on viral DNA to inhibit its replication 11,12 .…”

“…12 Foscarnet (phosphonoformic acid) and cidofovir are often used as treatments for herpetic lesions in patients with antiviral resistance. They function by acting on viral DNA to inhibit its replication 11,12 . Nevertheless, in clinical practice, these drugs are frequently associated with a high risk of toxicity, particularly nephrotoxicity 13 .…”

Advancement on Sustained Antiviral Ocular Drug Delivery for Herpes Simplex Virus Keratitis: Recent Update on Potential Investigation

“…Alvarez et al explained that approximately 3.5-10% of immunocompromised patients and 1% of immunocompetent patients reported resistance [17]. A novel approach in real-time cell analysis (RTCA) with a rapid result test compared to the gold standard phenotypic plaque reduction assay (PRA) is now emerging in the clinical field to encourage the screening of resistance to antivirals and provide a better treatment to patients [23][24][25].…”

Acyclovir‐resistant HSV‐1 isolates among immunocompromised patients in southern Taiwan: Low prevalence and novel mutations

“…7 Prolonged treatment of antiviral agents may result in the selection of viral isolates with reduced drug susceptibility and the emergence of drug-resistant mutants. Although the prevalence rate of HSV resistance to ACV is low (0.2%−0.7%) in immunocompetent patients, 8,9 the prevalence rate of ACV-resistant isolates in immunocompromised patients is from 3.5% to 17% 1,[9][10][11][12][13][14][15] and can be up to 28% (11/39) to 46.5% (26/56) among allogeneic hematopoietic stem cell transplantation (HSCT) patients. 16,17 In clinical HSV isolates, 95% of the resistance cases to ACV are mediated by mutations in the UL23 gene with single-base insertion/deletion, leading to a shift of the translational reading frame of the UL23 gene or missense point mutations.…”