Role of hepatitis B virus genetic barrier in drug-resistance and immune-escape development

Svicher, Valentina; Cento, Valeria; Salpini, Romina; Mercurio, Fabio; Fraune, M.; Beggel, Bastian; Han, Yue; Gori, Caterina; Wittkop, Linda; Bertoli, Ada; Micheli, Valeria; Gubertini, G.; Longo, Roberta; Romanò, Sara; Visca, M.; Gallinaro, Valentina; Marino, Nicoletta; Mazzotta, Francesco; Sanctis, Giuseppe Maria De; Fleury, Hervé; Trimoulet, Pascale; Angélico, M.; Cappiello, Giuseppina; Zhang, Xin Xin; Verheyen, Jens; Ceccherini‐Silberstein, Francesca; Perno, Carlo Federico

doi:10.1016/j.dld.2011.07.002

Cited by 28 publications

(25 citation statements)

References 36 publications

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“…Moreover, all of them had T131N mutations in the S region. Interestingly, this mutation has been found in patients infected with genotype A or G, and has been involved in immune escape 40 . In this study, one HBsAg positive woman reported previous hepatitis B vaccination.…”

Section: Discussionmentioning

confidence: 99%

Viral hepatitis in female sex workers using the Respondent-Driven Sampling

et al. 2017

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OBJECTIVETo estimate the prevalence of hepatitis B virus and C virus infections and their genotypes and analyze the risk factors for the markers of exposure to hepatitis B virus in female sex workers in a region of intense sex trade.METHODSThis is a cross-sectional study performed with four hundred and two female sex workers in Goiânia, Brazil. Data have been collected using the Respondent-Driven Sampling. The women have been interviewed and tested for markers of hepatitis B and C viruses. Positive samples have been genotyped. The data have been analyzed using the Respondent-Driven Sampling Analysis Tool, version 5.3, and Stata 11.0.RESULTSThe adjusted prevalence for hepatitis B virus and C virus were 17.1% (95%CI 11.6–23.4) and 0.7% (95%CI 0.1–1.5), respectively. Only 28% (95%CI 21.1–36.4) of the participants had serological evidence of vaccination against hepatitis B virus. Being older (> 40 years), being single, having a history of blood transfusion and use of cocaine, and ignoring the symptoms of sexually transmitted infections were associated with positivity for hepatitis B virus (p < 0.05). We have detected the subgenotype A1 of hepatitis B virus (n = 3) and the subtypes of hepatitis C virus 1a (n = 3) and 1b (n = 1).CONCLUSIONSWe can observe a low prevalence of infection of hepatitis B and C viruses in the studied population. However, the findings of the analysis of the risk factors show the need for more investment in prevention programs for sexual and drug-related behavior, as well as more efforts to vaccinate this population against hepatitis B. The genotypes of the hepatitis B virus and C virus identified are consistent with those circulating in Brazil.

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Section: Discussionmentioning

confidence: 99%

Viral hepatitis in female sex workers using the Respondent-Driven Sampling

et al. 2017

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“…With an HIV and HBV model (van de Vijver et al, 2006;Svicher et al, 2011), we analyzed the genetic barrier with the m.s. calculation, assigning different values for the type of nucleotide substitutions, because transitions, rather than transversions, were more likely to occur in HCV (Powdrill et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Primary resistance mutations and/or natural polymorphisms were identified by visual inspection. The HCV genetic barrier was evaluated using the minimal score calculation: a score of 1 was assigned to each transition (A-G and C-T), and a score of 2.5 to each transversion (A-C, A-T, G-C and C-T) (van de Vijver et al, 2006, Svicher et al, 2011.…”

Section: Methodsmentioning

confidence: 99%

HCV-1b intra-subtype variability: Impact on genetic barrier to protease inhibitors

Ferraro

Urone

Marco

et al. 2014

Infection, Genetics and Evolution

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a b s t r a c tDue to error-prone RNA polymerase and the lack of proofreading mechanisms, to the spread worldwide and probable long-term presence in human population, HCV showed a high degree of inter-and intrasubtype genetic variability.Protease inhibitors (PIs), a new class of drugs, have been designed specifically on the HCV genotype 1 NS3 protease three-dimensional structure. The viral genetic barrier limits the efficacy of PIs, and fourteen loci in the HCV NS3 gene are involved in resistance to PIs. A sensitive method (15 UI/ml) for study the HCV genetic profile of 125 strains from patients naïve to PIs, was developed through the use of new degenerate primers for subtype 1b.We observed the presence of naturally resistance-associated variants in 14% of the HCV strains (V36L, F43S, T54S, I153V, R155Q, D168A/G). T54S was the most common mutation (4%) detected.We investigated, through minimal score (m.s.) calculating, how the HCV intra-subtype 1b variability modifies the genetic barrier to PIs. For >60% of strains a single transition (m.s. of 1) was required for selection of low to medium resistance mutations, while more than one transition/transversion (m.s. P2.5) or one transition plus one transversion (m.s. P3.5) was necessary for most of the high level PI-resistantassociated mutations, except for A156V, for which a single transition was sufficient (m.s. of 1). However, the presence at locus 36 of the amino acid polymorphism S36 in one case and the wild type V36 in 6 isolates, encoded by unusual GTA or GTG codons, might determined a higher probability of V36L/M mutations because of the reduction of the genetic barrier. Instead, the presence of the CGA and CGT codons in the 155 th position increases the genetic barrier for R155M or R155Q/M.The large intra-subtype variability, suggests that a routine baseline resistance test must be used before PIs-treatment.

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“…These events may be linked to the emergence of drug-resistant variants during antiviral therapy (Litwin et al, 2005, Villet et al, 2009, Billioud et al, 2012). Recently, Svicher et al reported the synergistic effect of the genetic barrier and the S/P overlap on the development of drug resistance and immune escape (Svicher et al, 2011). The selection of a long-term therapy with a high barrier to resistance can determine the success of this therapy (Gish et al, 2012).…”

Section: Hbv Serotypes and Genotypesmentioning

confidence: 99%

Antiviral therapies: Focus on hepatitis B reverse transcriptase

Michailidis

Kirby

Hachiya

et al. 2012

The International Journal of Biochemistry & Cell Biology

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Hepatitis B virus (HBV) is the etiologic agent of mankind’s most serious liver disease. While the availability of a vaccine has reduced the number of new HBV infections, the vaccine does not benefit the approximately 350 million people already chronically infected by the virus. Most of the drugs approved by the FDA for the treatment of hepatitis B target the reverse transcriptase (RT or P gene product) and are nucleoside RT inhibitors (NRTIs) that suppress viral replication. However, prolonged monotherapies directed against a single target result in the emergence of viral resistance. HBV genotypic differences affect NRTI resistance, and because the reading frames of the S (surface antigen) and P genes partially overlap, genomic differences that affect the surface of the virus may also alter the viral polymerase sequence, function and drug susceptibility. The scope of this review is to assess the effects of HBV genotypic variation on the development of drug resistance to NRTIs. Some RT residues that vary among different genotypes are in the vicinity of residues that mutate and give rise to NRTI resistance. Interactions between these amino acids can help explain the effect of HBV genotype on the development of NRTI resistance during antiviral therapies, and might help in the design of improved therapeutic strategies.

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Role of hepatitis B virus genetic barrier in drug-resistance and immune-escape development

Cited by 28 publications

References 36 publications

Viral hepatitis in female sex workers using the Respondent-Driven Sampling

Viral hepatitis in female sex workers using the Respondent-Driven Sampling

HCV-1b intra-subtype variability: Impact on genetic barrier to protease inhibitors

Antiviral therapies: Focus on hepatitis B reverse transcriptase

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