ACV 1

Infections due to herpes simplex virus (HSV) resistant to acyclovir (ACV) represent an important clinical concern in immunocompromised patients. In order to switch promptly to an appropriate treatment, rapid viral susceptibility assays are required. We developed herein a genotyping analysis focusing on thymidine kinase gene (TK) mutations in order to detect acyclovir-resistant HSV in clinical specimens. A total of 85 HSV-1 positive specimens collected from 69 patients were analyzed. TK gene could be sequenced directly for 81 clinical specimens (95%) and 68 HSV-1 specimens could be characterized as sensitive or resistant by genotyping (84%). Genetic characterization of 67 susceptible HSV-1 specimens revealed 10 polymorphisms never previously described. Genetic characterization of 14 resistant HSV-1 revealed 12 HSV-1 with either TK gene additions/deletions (8 strains) or substitutions (4 strains) and 2 HSV-1 with no mutation in the TK gene. DNA polymerase gene was afterwards explored. With this rapid PCR-based assay, ACV-resistant HSV could be detected directly in clinical specimens within 24 h.

Twenty-four strains of acyclovir (ACV)-resistant (ACV(r)) herpes simplex virus type 1 (HSV-1) were generated from the HSV-1 TAS strain by exposure to ACV, and the genotype and phenotype of the thymidine kinase (TK) from these mutants were analyzed. The TK polypeptide of the ACV(r) HSV-1 strains was examined by Western blot using an anti-HSV-1 TK rabbit serum. The sensitivity of each strain to ACV, foscarnet and cidofovir (CDV) was also determined. A single guanine (G) insertion or a single cytosine (C) deletion was detected in 12 of the 24 ACV(r) strains at the G or C homopolymer stretches within the TK gene. Genotypic analysis predicted that two thirds of the ACV(r) HSV-1 strains expressed truncated TK polypeptides, while one third expressed viral TK polypeptide with a single amino acid substitution at various sites. Western blot abnormalities in the viral TK polypeptides were identified in 21 ACV(r) strains. There was an inverse correlation between the susceptibility of the HSV-1 mutant strains to ACV and that to CDV. Nucleotide sequencing of the TK gene and Western blot analysis of the viral TK polypeptides are considered to be one of the methods for predicting virus sensitivity to ACV and CDV.

Metabolic syndrome is a serious consequence of obesity characterized by increased cardiovascular risk factors such as hypertension, dyslipidemia, and glucose intolerance. While diets enriched with natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested, in this study, whether a daily dosage of Apple Cider Vinegar (ACV) would affect cardiovascular risk factor associated with obesity in high-fat diet (HFD)-induced hyperlipidemic Wistar rats. Obese rats showed increased serum total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), very low density lipoprotein (VLDL) and atherogenic index after 6 and 9 weeks of being fed an HFD. Importantly, ACV ameliorated all of these parameters significantly. Oxidative stress already developed after 6 weeks of HFD and was significantly reduced by daily doses of ACV. Oral administration of ACV normalized various biochemical and metabolic changes since it exhibited a very significant (P < .001) reduction in malondialdehyde levels, whereas an increase in thiol group concentrations and antioxidant status (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT] activities and vitamin E concentrations). In addition, a modulation in trace element levels was observed when compared with HFD groups. These findings suggested that HFD alters the oxidant-antioxidant balance, as evidenced by a reduction in the antioxidant enzyme activities and vitamin E level, and enhanced lipid peroxidation. ACV can be beneficial for the suppression of obesity-induced oxidative stress in HFD rats through the modulating antioxidant defense system and reduces the risk of obesity-associated diseases by preventing the atherogenic risk.

Herpes simplex virus type 1 (HSV-1) is an important human pathogenic virus. It is urgent to develop novel antiviral targets because of the limited treatment options and the emergence of drug resistant strains. In this study, we tested the antiviral activity of lupeol, a triterpenoid compound, against HSV-1 and acyclovir (ACV) resistant strains. Lupeol significantly inhibited HSV-1 (F strain) and ACV-resistant strains including HSV-1/106, HSV-1/153, and HSV-1/Blue. Lupeol activity of the HSV-1α0 and α4 promoters, therefore down regulating the expression of the α0, α4, and α27 genes. Collectively, lupeol showed strong antiviral activity against HSV-1 and ACV-resistant strains, and could be a promising therapeutic candidate for HSV-1 pathogenesis. Keywords: herpes simplex virus 1; lupeol; ACV-resistant strains; promoter.