Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates
Abstract Background We evaluated the frequency of naturally occurring resistance associated substitutions (RASs) and their characteristic of polymorphic or non-polymorphic amino acid change to direct acting antivirals (DAAs) in NS5b HCV subtypes 1a and 1b according to different geographic origin of...
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | Virology Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12985-018-1054-z |
| _version_ | 1811289494796632064 |
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| author | Sabrina Bagaglio Caterina Uberti-Foppa Alessandro Olgiati Emanuela Messina Hamid Hasson Camilla Ferri Giulia Morsica |
| author_facet | Sabrina Bagaglio Caterina Uberti-Foppa Alessandro Olgiati Emanuela Messina Hamid Hasson Camilla Ferri Giulia Morsica |
| author_sort | Sabrina Bagaglio |
| collection | DOAJ |
| description | Abstract Background We evaluated the frequency of naturally occurring resistance associated substitutions (RASs) and their characteristic of polymorphic or non-polymorphic amino acid change to direct acting antivirals (DAAs) in NS5b HCV subtypes 1a and 1b according to different geographic origin of isolates. Methods Using a public database we retrieved 738 worldwide NS5b sequences (for which was available the geographic origin) from HCV genotype (G)1 infected patients naive to DAAs. NS5b sequences clustering with G1a were more conserved in regard of RASs than G1b isolates, (14% vs 57% RASs, P < 0.0001). Results In G1a, RASs were differently distributed between isolates from Europe (24%) and USA, (12%) P = 0.0186. In particular, 421 V associated with resistance to non-nucleoside inhibitor beclabuvir was polymorphic in Europe and USA, being detected in 24% and 11% of sequences, respectively, P = 0.0140. In G1b, RASs were found in 45% of sequences from Europe, in 54% of isolates from USA and in 70% of sequences from Asia (P = 0.0051). The 316 N polymorphism was detected in 54% of Asian isolates and at lower frequency, in 28% of isolates from USA and in 20% of European sequences (P < 0.0001). Conclusions In conclusion, a higher prevalence of RASs in G1b respect to G1a was found and a geographical distribution of RASs and polymorphic aa changes was observed in G1a as well in G1b. The clinical and therapeutic impact of the geographic distribution of RASs to polymerase inhibitors remains to be established, particularly in patients with virologic failure to DAAs and/or advanced liver disease. |
| first_indexed | 2024-04-13T03:55:48Z |
| format | Article |
| id | doaj.art-ae0393b2d54c4670ae1ba9cc569af5c3 |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-04-13T03:55:48Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-ae0393b2d54c4670ae1ba9cc569af5c32022-12-22T03:03:39ZengBMCVirology Journal1743-422X2018-09-011511710.1186/s12985-018-1054-zNatural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolatesSabrina Bagaglio0Caterina Uberti-Foppa1Alessandro Olgiati2Emanuela Messina3Hamid Hasson4Camilla Ferri5Giulia Morsica6Division of Infectious Diseases, Ospedale San RaffaeleVita Salute UniversityDivision of Infectious Diseases, Ospedale San RaffaeleDivision of Infectious Diseases, Ospedale San RaffaeleDivision of Infectious Diseases, Ospedale San RaffaelePharmacy, Ospedale San RaffaeleDivision of Infectious Diseases, Ospedale San RaffaeleAbstract Background We evaluated the frequency of naturally occurring resistance associated substitutions (RASs) and their characteristic of polymorphic or non-polymorphic amino acid change to direct acting antivirals (DAAs) in NS5b HCV subtypes 1a and 1b according to different geographic origin of isolates. Methods Using a public database we retrieved 738 worldwide NS5b sequences (for which was available the geographic origin) from HCV genotype (G)1 infected patients naive to DAAs. NS5b sequences clustering with G1a were more conserved in regard of RASs than G1b isolates, (14% vs 57% RASs, P < 0.0001). Results In G1a, RASs were differently distributed between isolates from Europe (24%) and USA, (12%) P = 0.0186. In particular, 421 V associated with resistance to non-nucleoside inhibitor beclabuvir was polymorphic in Europe and USA, being detected in 24% and 11% of sequences, respectively, P = 0.0140. In G1b, RASs were found in 45% of sequences from Europe, in 54% of isolates from USA and in 70% of sequences from Asia (P = 0.0051). The 316 N polymorphism was detected in 54% of Asian isolates and at lower frequency, in 28% of isolates from USA and in 20% of European sequences (P < 0.0001). Conclusions In conclusion, a higher prevalence of RASs in G1b respect to G1a was found and a geographical distribution of RASs and polymorphic aa changes was observed in G1a as well in G1b. The clinical and therapeutic impact of the geographic distribution of RASs to polymerase inhibitors remains to be established, particularly in patients with virologic failure to DAAs and/or advanced liver disease.http://link.springer.com/article/10.1186/s12985-018-1054-zAnti-HCV direct acting antivirals (DAAs)Geographic distributionHCV genotypeNS5b polymerase inhibitorsResistance associated substitutions (RASs) |
| spellingShingle | Sabrina Bagaglio Caterina Uberti-Foppa Alessandro Olgiati Emanuela Messina Hamid Hasson Camilla Ferri Giulia Morsica Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates Virology Journal Anti-HCV direct acting antivirals (DAAs) Geographic distribution HCV genotype NS5b polymerase inhibitors Resistance associated substitutions (RASs) |
| title | Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates |
| title_full | Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates |
| title_fullStr | Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates |
| title_full_unstemmed | Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates |
| title_short | Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates |
| title_sort | natural polymorphisms in the resistance associated sites of hcv g1 ns5b domain and correlation with geographic origin of hcv isolates |
| topic | Anti-HCV direct acting antivirals (DAAs) Geographic distribution HCV genotype NS5b polymerase inhibitors Resistance associated substitutions (RASs) |
| url | http://link.springer.com/article/10.1186/s12985-018-1054-z |
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