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.
Genetic divergence of HIV-1 B subtype in Italy over the years 2003–2016 and impact on CTL escape prevalence / C. Alteri, L. Fabeni, R. Scutari, G. Berno, D. Di Carlo, C. Gori, A. Bertoli, A. Vergori, I. Mastrorosa, R. Bellagamba, C. Mussini, M. Colafigli, F. Montella, A. Pennica, C.M. Mastroianni, E. Girardi, M. Andreoni, A. Antinori, V. Svicher, F. Ceccherini-Silberstein, C.F. Perno, M.M. Santoro. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 8:1(2018 Oct 24).
|Titolo:||Genetic divergence of HIV-1 B subtype in Italy over the years 2003–2016 and impact on CTL escape prevalence|
ALTERI, CLAUDIA (Primo) (Corresponding)
PERNO, CARLO FEDERICO (Penultimo)
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Data di pubblicazione:||24-ott-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/s41598-018-34058-7|
|Appare nelle tipologie:||01 - Articolo su periodico|