Resistance-Associated Variants in HCV Subtypes 1a and 1b Detected by Ion Torrent Sequencing Platform

Gaspareto, Karine Vieira; Ribeiro, Roberto; Malta, Fernanda de Mello; Gomes‐Gouvêa, Michele Soares; Muto, Nair Hideko; Romano, Camila Malta; Mendes-Corrêa, Maria Cássia; Carrilho, Flair José; Sabino, Éster Cerdeira; Pinho, João Renato Rebello

doi:10.3851/imp3057

Cited by 11 publications

(14 citation statements)

References 42 publications

(49 reference statements)

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“…Finally, NS5B S282T variant, a signature NS5B mutation known as being associated to resistance in in vitro SOF studies, was not detected in any patient at baseline. This finding is similar to data coming from the majority of previous in vivo studies …”

Section: Discussionsupporting

confidence: 92%

“…Among the positions analyzed for NS5A, the L31M and Y93H ones have been evaluated as relevant resistance mutations since their baseline presence significantly affects DAA treatment outcomes . In the present study, the prevalence of L31M (6.7%) seemed to be higher than the one observed by most researchers, who found a prevalence around 0%‐5% . On the contrary, the frequency of Y93H (2.3%) did not reach the prevalence reported in Asiatic countries (10%‐19%) but was similar to that observed in studies carried out in Brazil .…”

Section: Discussionsupporting

confidence: 74%

“…While several works had determined the worldwide prevalence of NS5A/B RASs, the information coming from South América is very scarce . It is known that RASs prevalence in both proteins varies by geographic region.…”

Section: Discussionmentioning

confidence: 99%

“…Up to date, similarly to NS5A, the prevalence of NS5B RASs has been well characterized in Europe, North America, and Asia, but less is known about their presence in other South American countries and, especially, in Argentina . A 6.3% of HCV‐1 infected patients were identified as presenting RASs in the analyzed NS5B region.…”

Section: Discussionmentioning

confidence: 99%

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Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

Martínez

García

Ridruejo

et al. 2019

Journal of Medical Virology

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Direct acting antiviral (DAA) therapy against hepatitis C virus (HCV) increases sustained virologic response rates. Nevertheless, drug resistance has occasionally been associated with failure to DAA. However, the information about the prevalence of NS5A and NS5B resistance-associated substitutions (RASs) in Argentina is very scarce. In this study, we determine the prevalence of NS5A and NS5B resistances to treatment in Argentinean DAA treatment-naïve patients chronically infected with genotype 1 (HCV-1). In this retrospective cross-sectional study, 108 HCV-1-infected patients were studied. RASs in NS5A and NS5B were analyzed by Sanger at baseline and phylogenetic analysis was performed. NS5A and NS5B RASs were detected in 25.8% and 6.3% of the analyzed sequences, respectively. The most frequent primary RASs for NS5A were L31M (7.5%) and Y93H (3.2%) and for NS5B was L159F (3.8%). No association between the presence of RASs and the outcome of DAA treatment was found in this study. Additionally, most of the Argentinean samples were randomly distributed among sequences around the world in the phylogenetic analysis. Only one significant Argentinean cluster was observed in both regions but without any particular RASs pattern. Baseline RASs in NS5A and NS5B were frequently observed in HCV-1-infected patients from Buenos Aires, Argentina but not related to treatment outcome. No clusters related to RASs transmission were observed in the phylogenetic analysis. The frequency of RASs detected in this study supports the need for more molecular epidemiology studies on RASs to adjust local treatment guidelines with the incorporation of autochthonous data. K E Y W O R D Sdirect-acting antiviral, hepatitis C virus, molecular epidemiology, therapy

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

Martínez

García

Ridruejo

et al. 2019

Journal of Medical Virology

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“…Protons released during nucleotide incorporation are detected using an ion sensor, which can measure slight shifts in pH ( Merriman et al, 2012 , Reuter et al, 2015 ). Rapid sequencing runs make these sequencers particularly useful for the targeted detection of viruses in clinical samples like HIV Archer et al, 2012 , Chang et al, 2013 , Gibson et al, 2014 ), hepatitis B virus ( Yan et al, 2015 ), HCV ( Gaspareto et al, 2016 , Marascio et al, 2016 ), and the rapid genome sequencing of several viruses including the toscana virus ( Nougairede et al, 2013 ), polyomavirus ( Anthony et al, 2013 ), porcine reproductive and respiratory syndrome virus ( Kvisgaard et al, 2013 ), orthoreovirus ( Steyer et al, 2013 ), bluetongue virus ( Lorusso et al, 2014 ), rotavirus ( Ndze et al, 2014 ; Nyaga et al, 2014 ), influenza virus ( Van den Hoecke et al, 2015 ) etc. Although, some studies used this technology to study viromes in skin ( Bzhalava et al, 2013 ), ticks ( Tokarz et al, 2014 ; Xia et al, 2015 ), gut virome in piglets ( Karlsson et al, 2016 ) and seals ( Kluge et al, 2016 ), this platform is not the ideal choice for virome study in human clinical samples due to lower outputs.…”

Section: Evolution and Use Of Sequencing Technologies For Virus Metagmentioning

confidence: 99%

Evolution of selective-sequencing approaches for virus discovery and virome analysis

2017

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Recent advances in sequencing technologies have transformed the field of virus discovery and virome analysis. Once, mostly confined to the traditional Sanger sequencing based individual virus discovery, is now entirely replaced by high throughput sequencing (HTS) based virus metagenomics that can be used to characterize the nature and composition of entire viromes. To better harness the potential of HTS for study of viromes, sample preparation methodologies used different refinements to exclude amplification of non-viral components that can overshadow low-titer viruses. These virus-sequence enrichment approaches mostly focused on the sample preparation methods, like enzymatic digestion of non-viral nucleic acids and size exclusion of non-viral constituents by column filtration, ultrafiltration or density centrifugation. However, recently an approach of virus-sequence enrichment called virome-capture sequencing, focused on the amplification or HTS library preparation stage, was shown to increase the ability of virome characterization. This new approach has the potential to further transform the field of virus discovery and virome analysis, but its technical complexity and sequence-dependence warrants further improvements. In this review we have listed the different methods, their applications and evolution, for selective sequencing based virome analysis and also the major refinements needed to harness the full potential of HTS for virome analysis.

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Prevalence of naturally occurring amino acid substitutions associated with resistance to hepatitis C virus NS3/NS4A protease inhibitors in São Paulo state

et al. 2018

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Hepatitis C (HCV)-infected patients are treated with direct-acting antiviral agents (DAAs) in highly effective, well-tolerated, all-oral regimens. However, naturally occurring resistance-associated amino acid substitutions (RASs) may be selected during treatment. This study aimed to screen naturally occurring RASs NS3/NS4A inhibitors (PIs). Samples were obtained from DAA naïve patients, living in São Paulo state, Brazil. Screening for RASs in the HCV NS3 region was conducted in 859 samples from HCV-infected patients, of which 425 and 434 samples were subtype 1a and 1b, respectively. HCV-RNA was extracted, amplified, and sequenced. The overall prevalence of RASs to HCV PIs was 9.4%. The following RASs were observed in HCV-1a subtype infected patients: V36L (2.6%), T54S (1.6%), V55I/A (1.2% / 8.9%, respectively), Q80K (2.1%), R155K (0.5%), and D168E (0.2%); and in HCV-1b infected patients: V36L (0.7%), T54A/S (0.2% and 0.5%, respectively), V55A (0.5%), Q80K (0.2%), D168E (1.6%), and M175L (0.5%). HCV 1a infected subjects had higher serum viral load than that seen in patients infected with HCV 1b. There was no difference between the proportions of NS3 RASs with regards to geographic distribution within the investigated areas. These findings should be supported by additional studies in Brazil to help in the formation of local clinical guidelines for managing hepatitis C.

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Resistance-Associated Variants in HCV Subtypes 1a and 1b Detected by Ion Torrent Sequencing Platform

Cited by 11 publications

References 42 publications

Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

Evolution of selective-sequencing approaches for virus discovery and virome analysis

Prevalence of naturally occurring amino acid substitutions associated with resistance to hepatitis C virus NS3/NS4A protease inhibitors in São Paulo state

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