Dynamic features of the selective pressure on the human immunodeficiency virus type 1 (HIV-1) gp120 CD4-binding site in a group of long term non progressor (LTNP) subjects

Canducci Filippo, Marinozzi Maria, Sampaolo Michela, Berrè Stefano, Bagnarelli Patrizia, Degano Massimo, Gallotta Giulia, Mazzi Benedetta, Lemey Philippe, Burioni Roberto, Clementi Massimo

Description

The characteristics of intra-host human immunodeficiency virus type 1 (HIV-1) env evolution were evaluated in untreated HIV-1-infected subjects with different patterns of disease progression, including 2 normal progressor [NP], and 5 Long term non-progressor [LTNP] patients. High-resolution phylogenetic analysis of the C2-C5 env gene sequences of the replicating HIV-1 was performed in sequential samples collected over a 3–5 year period; overall, 301 HIV-1 genomic RNA sequences were amplified from plasma samples, cloned, sequenced and analyzed. Firstly, the evolutionary rate was calculated separately in the 3 codon positions. In all LTNPs, the 3 rd codon mutation rate was equal or even lower than that observed at the 1 st and 2 nd positions (p = 0.016), thus suggesting strong ongoing positive selection. A Bayesian approach and a maximum-likelihood (ML) method were used to estimate the rate of virus evolution within each subject and to detect positively selected sites respectively. A great number of N-linked glycosylation sites under positive selection were identified in both NP and LTNP subjects. Viral sequences from 4 of the 5 LTNPs showed extensive positive selective pressure on the CD4-binding site (CD4bs). In addition, localized pressure in the area of the IgG-b12 epitope, a broad neutralizing human monoclonal antibody targeting the CD4bs, was documented in one LTNP subject, using a graphic colour grade 3-dimensional visualization. Overall, the data shown here documenting high selective pressure on the HIV-1 CD4bs of a group of LTNP subjects offers important insights for planning novel strategies for the immune control of HIV-1 infection.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 17
• Langue: English

Extrait

Retrovirology

BioMedCentral

Open Access Research Dynamic features of the selective pressure on the human immunodeficiency virus type 1 (HIV1) gp120 CD4binding site in a group of long term non progressor (LTNP) subjects 1 11 Filippo Canducci*, Maria Chiara Marinozzi, Michela Sampaolo, 1 23 4 Stefano Berrè, Patrizia Bagnarelli, Massimo Degano, Giulia Gallotta, 5 61 Benedetta Mazzi, Philippe Lemey, Roberto Burioniand 1 Massimo Clementi

1 2 Address: Laboratoriodi Microbiologia e Virologa, Università VitaSalute San Raffaele, Milan, Italy,Istituto di Microbiologia, Università 3 4 Politecnica delle Marche, Ancona, Italy,Unità di Biocristallografia, Istituto Scientifico San Raffaele, Milan, Italy,Dipartimento di Malattie 5 Infettive, Università VitaSalute San Raffaele, Milan, Italy,Laboratorio di Ematologia Molecolare, Istituto Scientifico San Raffaele, Milan, Italy and 6 Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium

Email: Filippo Canducci*  [e-mail]; Maria Chiara Marinozzi  [e-mail]; Michela Sampaolo  [e-mail]; Stefano Berrè  [e-mail]; Patrizia Bagnarelli  [e-mail]; Massimo Degano  [e-mail]; Giulia Gallotta  [e-mail]; Benedetta Mazzi  [e-mail]; Philippe Lemey  [e-mail]; Roberto Burioni  [e-mail]; Massimo Clementi  [e-mail] * Corresponding author

Published: 15 January 2009Received: 6 October 2008 Accepted: 15 January 2009 Retrovirology2009,6:4 doi:10.1186/1742469064 This article is available from: http://www.retrovirology.com/content/6/1/4 © 2009 Canducci et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract The characteristics of intrahost human immunodeficiency virus type 1 (HIV1)envevolution were evaluated in untreated HIV1infected subjects with different patterns of disease progression, including 2 normal progressor [NP], and 5 Long term nonprogressor [LTNP] patients. High resolution phylogenetic analysis of the C2C5envgene sequences of the replicating HIV1 was performed in sequential samples collected over a 3–5 year period; overall, 301 HIV1 genomic RNA sequences were amplified from plasma samples, cloned, sequenced and analyzed. Firstly, the rd evolutionary rate was calculated separately in the 3 codon positions. In all LTNPs, the 3codon st nd mutation rate was equal or even lower than that observed at the 1and 2positions (p = 0.016), thus suggesting strong ongoing positive selection. A Bayesian approach and a maximumlikelihood (ML) method were used to estimate the rate of virus evolution within each subject and to detect positively selected sites respectively. A great number of Nlinked glycosylation sites under positive selection were identified in both NP and LTNP subjects. Viral sequences from 4 of the 5 LTNPs showed extensive positive selective pressure on the CD4binding site (CD4bs). In addition, localized pressure in the area of the IgGb12 epitope, a broad neutralizing human monoclonal antibody targeting the CD4bs, was documented in one LTNP subject, using a graphic colour grade 3dimensional visualization. Overall, the data shown here documenting high selective pressure on the HIV1 CD4bs of a group of LTNP subjects offers important insights for planning novel strategies for the immune control of HIV1 infection.

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