Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence

Claudia Alteri, Lavinia Fabeni, Rossana Scutari, Giulia Berno, Domenico Di Carlo, Caterina Gori, Ada Bertoli, Alessandra Vergori, Ilaria Mastrorosa, Rita Bellagamba, Cristina Mussini, Manuela Colafigli, Francesco Montella, Alfredo Pennica, Claudio Maria Mastroianni, Enrico Girardi, Massimo Andreoni, Andrea Antinori, Valentina Svicher, Francesca Ceccherini-SilbersteinCarlo Federico Perno, Maria Mercedes Santoro

Research output: Contribution to journalArticle

Abstract

HIV-1 is characterized by high genetic variability, with implications for spread, and immune-escape selection. Here, the genetic modification of HIV-1 B subtype over time was evaluated on 3,328 pol and 1,152 V3 sequences belonging to B subtype and collected from individuals diagnosed in Italy between 2003 and 2016. Sequences were analyzed for genetic-distance from consensus-B (Tajima-Nei), non-synonymous and synonymous rates (dN and dS), CTL escapes, and intra-host evolution over four time-spans (2003-2006, 2007-2009, 2010-2012, 2013-2016). Genetic-distance increased over time for both pol and V3 sequences (P < 0.0001 and 0.0003). Similar results were obtained for dN and dS. Entropy-value significantly increased at 16 pol and two V3 amino acid positions. Seven of them were CTL escape positions (protease: 71; reverse-transcriptase: 35, 162, 177, 202, 207, 211). Sequences with ≥3 CTL escapes increased from 36.1% in 2003-2006 to 54.0% in 2013-2016 (P < 0.0001), and showed better intra-host adaptation than those containing ≤2 CTL escapes (intra-host evolution: 3.0 × 10-3 [2.9 × 10-3-3.1 × 10-3] vs. 4.3 × 10-3 [4.0 × 10-3-5.0 × 10-3], P[LRT] < 0.0001[21.09]). These data provide evidence of still ongoing modifications, involving CTL escape mutations, in circulating HIV-1 B subtype in Italy. These modifications might affect the process of HIV-1 adaptation to the host, as suggested by the slow intra-host evolution characterizing viruses with a high number of CTL escapes.

Original languageEnglish
Pages (from-to)15739
Number of pages12
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Oct 24 2018

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Italy
HIV-1
RNA-Directed DNA Polymerase
Entropy
Peptide Hydrolases
Viruses
Amino Acids
Mutation

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Alteri, C., Fabeni, L., Scutari, R., Berno, G., Di Carlo, D., Gori, C., ... Santoro, M. M. (2018). Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence. Scientific Reports, 8(1), 15739. https://doi.org/10.1038/s41598-018-34058-7

Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence. / Alteri, Claudia; Fabeni, Lavinia; Scutari, Rossana; Berno, Giulia; Di Carlo, Domenico; Gori, Caterina; Bertoli, Ada; Vergori, Alessandra; Mastrorosa, Ilaria; Bellagamba, Rita; Mussini, Cristina; Colafigli, Manuela; Montella, Francesco; Pennica, Alfredo; Mastroianni, Claudio Maria; Girardi, Enrico; Andreoni, Massimo; Antinori, Andrea; Svicher, Valentina; Ceccherini-Silberstein, Francesca; Perno, Carlo Federico; Santoro, Maria Mercedes.

In: Scientific Reports, Vol. 8, No. 1, 24.10.2018, p. 15739.

Research output: Contribution to journalArticle

Alteri, C, Fabeni, L, Scutari, R, Berno, G, Di Carlo, D, Gori, C, Bertoli, A, Vergori, A, Mastrorosa, I, Bellagamba, R, Mussini, C, Colafigli, M, Montella, F, Pennica, A, Mastroianni, CM, Girardi, E, Andreoni, M, Antinori, A, Svicher, V, Ceccherini-Silberstein, F, Perno, CF & Santoro, MM 2018, 'Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence', Scientific Reports, vol. 8, no. 1, pp. 15739. https://doi.org/10.1038/s41598-018-34058-7
Alteri, Claudia ; Fabeni, Lavinia ; Scutari, Rossana ; Berno, Giulia ; Di Carlo, Domenico ; Gori, Caterina ; Bertoli, Ada ; Vergori, Alessandra ; Mastrorosa, Ilaria ; Bellagamba, Rita ; Mussini, Cristina ; Colafigli, Manuela ; Montella, Francesco ; Pennica, Alfredo ; Mastroianni, Claudio Maria ; Girardi, Enrico ; Andreoni, Massimo ; Antinori, Andrea ; Svicher, Valentina ; Ceccherini-Silberstein, Francesca ; Perno, Carlo Federico ; Santoro, Maria Mercedes. / Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence. In: Scientific Reports. 2018 ; Vol. 8, No. 1. pp. 15739.
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abstract = "HIV-1 is characterized by high genetic variability, with implications for spread, and immune-escape selection. Here, the genetic modification of HIV-1 B subtype over time was evaluated on 3,328 pol and 1,152 V3 sequences belonging to B subtype and collected from individuals diagnosed in Italy between 2003 and 2016. Sequences were analyzed for genetic-distance from consensus-B (Tajima-Nei), non-synonymous and synonymous rates (dN and dS), CTL escapes, and intra-host evolution over four time-spans (2003-2006, 2007-2009, 2010-2012, 2013-2016). Genetic-distance increased over time for both pol and V3 sequences (P < 0.0001 and 0.0003). Similar results were obtained for dN and dS. Entropy-value significantly increased at 16 pol and two V3 amino acid positions. Seven of them were CTL escape positions (protease: 71; reverse-transcriptase: 35, 162, 177, 202, 207, 211). Sequences with ≥3 CTL escapes increased from 36.1{\%} in 2003-2006 to 54.0{\%} in 2013-2016 (P < 0.0001), and showed better intra-host adaptation than those containing ≤2 CTL escapes (intra-host evolution: 3.0 × 10-3 [2.9 × 10-3-3.1 × 10-3] vs. 4.3 × 10-3 [4.0 × 10-3-5.0 × 10-3], P[LRT] < 0.0001[21.09]). These data provide evidence of still ongoing modifications, involving CTL escape mutations, in circulating HIV-1 B subtype in Italy. These modifications might affect the process of HIV-1 adaptation to the host, as suggested by the slow intra-host evolution characterizing viruses with a high number of CTL escapes.",
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T1 - Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence

AU - Alteri, Claudia

AU - Fabeni, Lavinia

AU - Scutari, Rossana

AU - Berno, Giulia

AU - Di Carlo, Domenico

AU - Gori, Caterina

AU - Bertoli, Ada

AU - Vergori, Alessandra

AU - Mastrorosa, Ilaria

AU - Bellagamba, Rita

AU - Mussini, Cristina

AU - Colafigli, Manuela

AU - Montella, Francesco

AU - Pennica, Alfredo

AU - Mastroianni, Claudio Maria

AU - Girardi, Enrico

AU - Andreoni, Massimo

AU - Antinori, Andrea

AU - Svicher, Valentina

AU - Ceccherini-Silberstein, Francesca

AU - Perno, Carlo Federico

AU - Santoro, Maria Mercedes

PY - 2018/10/24

Y1 - 2018/10/24

N2 - HIV-1 is characterized by high genetic variability, with implications for spread, and immune-escape selection. Here, the genetic modification of HIV-1 B subtype over time was evaluated on 3,328 pol and 1,152 V3 sequences belonging to B subtype and collected from individuals diagnosed in Italy between 2003 and 2016. Sequences were analyzed for genetic-distance from consensus-B (Tajima-Nei), non-synonymous and synonymous rates (dN and dS), CTL escapes, and intra-host evolution over four time-spans (2003-2006, 2007-2009, 2010-2012, 2013-2016). Genetic-distance increased over time for both pol and V3 sequences (P < 0.0001 and 0.0003). Similar results were obtained for dN and dS. Entropy-value significantly increased at 16 pol and two V3 amino acid positions. Seven of them were CTL escape positions (protease: 71; reverse-transcriptase: 35, 162, 177, 202, 207, 211). Sequences with ≥3 CTL escapes increased from 36.1% in 2003-2006 to 54.0% in 2013-2016 (P < 0.0001), and showed better intra-host adaptation than those containing ≤2 CTL escapes (intra-host evolution: 3.0 × 10-3 [2.9 × 10-3-3.1 × 10-3] vs. 4.3 × 10-3 [4.0 × 10-3-5.0 × 10-3], P[LRT] < 0.0001[21.09]). These data provide evidence of still ongoing modifications, involving CTL escape mutations, in circulating HIV-1 B subtype in Italy. These modifications might affect the process of HIV-1 adaptation to the host, as suggested by the slow intra-host evolution characterizing viruses with a high number of CTL escapes.

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