Project

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Host evolutionary genomics of HIV-1 and other retroviruses

English title Host evolutionary genomics of HIV-1 and other retroviruses
Applicant Telenti Amalio
Number 132863
Funding scheme Project funding
Research institution Institut de Microbiologie Faculté de Biologie et Médecine CHUV/Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Medical Microbiology
Start/End 01.11.2010 - 30.11.2013
Approved amount 543'018.00
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All Disciplines (2)

Discipline
Medical Microbiology
Genetics

Keywords (9)

HIV-1; comparative genomics; positive selection; retroviruses; evolution; retrovirus; red queen; large nested project; Swiss HIV Cohort Study

Lay Summary (English)

Lead
Evolutionary genetics is important for the understanding of HIV biology
Lay summary
Retroviruses have been intimately associated with the evolution of vertebrates. In many instances, they have effectively integrated in the host genome in a permanent fashion. Lentiviruses, a subgroup of the retroviruses that includes the human immunodeficiency virus HIV-1, infect numerous primate species in nature. The host, and in particularly humans, are expected to have built a dedicated system to assure effective defense and a peaceful coexistance with these ubiquitous infectious agents. It is reasonable to think that a species adaptation to retroviruses during history will modulate the response to modern retroviral infections - for example the response of humans to HIV-1. Indeed there are considerable differences in disease cause by lentiviruses across primate species, and across humans. The identification of the genetic differences underpinning inter- or intraspecies differences in susceptibility would greatly help the understanding of basic mechanisms of pathogenesis. This project will use tools of comparative genomics, and the complete genomes of 9 primates to understand the evolutionary characteristics of genes involved in pathogen response. In a second phase, the study will characterized the mutation burden in human genes involved in pathogen response by exploiting the data from 1000Genomes - the international project that aims at the detailed understanding of the structure and variation of the human genome. Lastly, the project will aim at the functional characterization of selected candidate genes and at the reconstruction of the ancestral states of host genes as well as of endogenous retroviruses integrated in the human genome. This work will generate a detailed annotation of the human genome in the context of evolution and of response to lentiviruses. Candidate genes will then be evaluate for a role in HIV-1 disease, and human variation in those genes will be assessed in their contribution to interindividual differences in susceptibility to infection and disease.
Direct link to Lay Summary Last update: 03.12.2012

Responsible applicant and co-applicants

Employees

Publications

Publication
24 hours in the life of HIV-1 in a T cell line.
Mohammadi Pejman, Desfarges Sébastien, Bartha István, Joos Beda, Zangger Nadine, Muñoz Miguel, Günthard Huldrych F, Beerenwinkel Niko, Telenti Amalio, Ciuffi Angela (2013), 24 hours in the life of HIV-1 in a T cell line., in PLoS pathogens, 9(1), 1003161-1003161.
A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.
Bartha István, Carlson Jonathan M, Brumme Chanson J, McLaren Paul J, Brumme Zabrina L, John Mina, Haas David W, Martinez-Picado Javier, Dalmau Judith, López-Galíndez Cecilio, Casado Concepción, Rauch Andri, Günthard Huldrych F, Bernasconi Enos, Vernazza Pietro, Klimkait Thomas, Yerly Sabine, O'Brien Stephen J, Listgarten Jennifer, Pfeifer Nico, Lippert Christoph, Fusi Nicolo, Kutalik Zoltán, Allen Todd M, Müller Viktor (2013), A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control., in eLife, 2, 01123-01123.
A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.
Lane Jérôme, McLaren Paul J, Dorrell Lucy, Shianna Kevin V, Stemke Amanda, Pelak Kimberly, Moore Stephen, Oldenburg Johannes, Alvarez-Roman Maria Teresa, Angelillo-Scherrer Anne, Boehlen Francoise, Bolton-Maggs Paula H B, Brand Brigit, Brown Deborah, Chiang Elaine, Cid-Haro Ana Rosa, Clotet Bonaventura, Collins Peter, Colombo Sara, Dalmau Judith, Fogarty Patrick, Giangrande Paul, Gringeri Alessandro, Iyer Rathi, Katsarou Olga (2013), A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A., in Human molecular genetics, 22(9), 1903-10.
Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls.
McLaren Paul J, Coulonges Cédric, Ripke Stephan, van den Berg Leonard, Buchbinder Susan, Carrington Mary, Cossarizza Andrea, Dalmau Judith, Deeks Steven G, Delaneau Olivier, De Luca Andrea, Goedert James J, Haas David, Herbeck Joshua T, Kathiresan Sekar, Kirk Gregory D, Lambotte Olivier, Luo Ma, Mallal Simon, van Manen Daniëlle, Martinez-Picado Javier, Meyer Laurence, Miro José M, Mullins James I, Obel Niels (2013), Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls., in PLoS pathogens, 9(7), 1003515-1003515.
Susceptibility and adaptation to human TRIM5α alleles at positive selected sites in HIV-1 capsid.
Rahm Nadia, Gfeller David, Snoeck Joke, Martinez Raquel, McLaren Paul J, Ortiz Millán, Ciuffi Angela, Telenti Amalio (2013), Susceptibility and adaptation to human TRIM5α alleles at positive selected sites in HIV-1 capsid., in Virology, 441(2), 162-70.
Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein.
Laguette Nadine, Rahm Nadia, Sobhian Bijan, Chable-Bessia Christine, Münch Jan, Snoeck Joke, Sauter Daniel, Switzer William M, Heneine Walid, Kirchhoff Frank, Delsuc Frédéric, Telenti Amalio, Benkirane Monsef (2012), Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein., in Cell host & microbe, 11(2), 205-17.
Host Genes Important to HIV Replication and Evolution.
Telenti Amalio, Johnson Welkin E (2012), Host Genes Important to HIV Replication and Evolution., in Cold Spring Harbor perspectives in medicine, 2(4), 007203-007203.
Siglec-1 is a novel dendritic cell receptor that mediates HIV-1 trans-infection through recognition of viral membrane gangliosides.
Izquierdo-Useros Nuria, Lorizate Maier, Puertas Maria C, Rodriguez-Plata Maria T, Zangger Nadine, Erikson Elina, Pino Maria, Erkizia Itziar, Glass Bärbel, Clotet Bonaventura, Keppler Oliver T, Telenti Amalio, Kräusslich Hans-Georg, Martinez-Picado Javier (2012), Siglec-1 is a novel dendritic cell receptor that mediates HIV-1 trans-infection through recognition of viral membrane gangliosides., in PLoS biology, 10(12), 1001448-1001448.
The role of tripartite motif family members in mediating susceptibility to HIV-1 infection.
Rahm Nadia, Telenti Amalio (2012), The role of tripartite motif family members in mediating susceptibility to HIV-1 infection., in Current opinion in HIV and AIDS, 7(2), 180-6.
Analysis of HIV-1 expression level and sense of transcription by high-throughput sequencing of the infected cell.
Lefebvre Gregory, Desfarges Sébastien, Uyttebroeck Frédéric, Muñoz Miguel, Beerenwinkel Niko, Rougemont Jacques, Telenti Amalio, Ciuffi Angela (2011), Analysis of HIV-1 expression level and sense of transcription by high-throughput sequencing of the infected cell., in Journal of virology, 85(13), 6205-11.
Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque.
Rotger Margalida, Dalmau Judith, Rauch Andri, McLaren Paul, Bosinger Steven E, Martinez Raquel, Sandler Netanya G, Roque Annelys, Liebner Julia, Battegay Manuel, Bernasconi Enos, Descombes Patrick, Erkizia Itziar, Fellay Jacques, Hirschel Bernard, Miró Jose M, Palou Eduard, Hoffmann Matthias, Massanella Marta, Blanco Julià, Woods Matthew, Günthard Huldrych F, de Bakker Paul, Douek Daniel C, Silvestri Guido (2011), Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque., in The Journal of clinical investigation, 121(6), 2391-400.
Copy number variation of KIR genes influences HIV-1 control.
Pelak Kimberly, Need Anna C, Fellay Jacques, Shianna Kevin V, Feng Sheng, Urban Thomas J, Ge Dongliang, De Luca Andrea, Martinez-Picado Javier, Wolinsky Steven M, Martinson Jeremy J, Jamieson Beth D, Bream Jay H, Martin Maureen P, Borrow Persephone, Letvin Norman L, McMichael Andrew J, Haynes Barton F, Telenti Amalio, Carrington Mary, Goldstein David B, Alter Galit, NIAID Center for HIV/AIDS Vaccine Immunology (2011), Copy number variation of KIR genes influences HIV-1 control., in PLoS biology, 9(11), 1001208-1001208.
Differential microRNA regulation of HLA-C expression and its association with HIV control.
Kulkarni Smita, Savan Ram, Qi Ying, Gao Xiaojiang, Yuki Yuko, Bass Sara E, Martin Maureen P, Hunt Peter, Deeks Steven G, Telenti Amalio, Pereyra Florencia, Goldstein David, Wolinsky Steven, Walker Bruce, Young Howard A, Carrington Mary (2011), Differential microRNA regulation of HLA-C expression and its association with HIV control., in Nature, 472(7344), 495-8.
Impact of phenotype definition on genome-wide association signals: empirical evaluation in human immunodeficiency virus type 1 infection.
Evangelou Evangelos, Fellay Jacques, Colombo Sara, Martinez-Picado Javier, Obel Niels, Goldstein David B, Telenti Amalio, Ioannidis John P A (2011), Impact of phenotype definition on genome-wide association signals: empirical evaluation in human immunodeficiency virus type 1 infection., in American journal of epidemiology, 173(11), 1336-42.
Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints.
Snoeck Joke, Fellay Jacques, Bartha István, Douek Daniel C, Telenti Amalio (2011), Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints., in Retrovirology, 8, 87-87.
Models of Protection Against HIV/SIV
Gianfranco Pancino, Guido Silvestri, Keith Fowke (2011), Models of Protection Against HIV/SIV, Academic Press, Canada.
Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction activities.
Bulliard Yannick, Narvaiza Iñigo, Bertero Alessandro, Peddi Shyam, Röhrig Ute F, Ortiz Millán, Zoete Vincent, Castro-Díaz Nataly, Turelli Priscilla, Telenti Amalio, Michielin Olivier, Weitzman Matthew D, Trono Didier (2011), Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction activities., in Journal of virology, 85(4), 1765-76.
Transcriptional profiling of CD4 T cells identifies distinct subgroups of HIV-1 elite controllers.
Vigneault Francois, Woods Matthew, Buzon Maria J, Li Chun, Pereyra Florencia, Crosby Seth D, Rychert Jennifer, Church George, Martinez-Picado Javier, Rosenberg Eric S, Telenti Amalio, Yu Xu G, Lichterfeld Mathias (2011), Transcriptional profiling of CD4 T cells identifies distinct subgroups of HIV-1 elite controllers., in Journal of virology, 85(6), 3015-9.
Unique spectrum of activity of prosimian TRIM5alpha against exogenous and endogenous retroviruses.
Rahm Nadia, Yap Melvyn, Snoeck Joke, Zoete Vincent, Muñoz Miguel, Radespiel Ute, Zimmermann Elke, Michielin Olivier, Stoye Jonathan P, Ciuffi Angela, Telenti Amalio (2011), Unique spectrum of activity of prosimian TRIM5alpha against exogenous and endogenous retroviruses., in Journal of virology, 85(9), 4173-83.
Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses.
Paust Silke, Gill Harvinder S, Wang Bao-Zhong, Flynn Michael P, Moseman E Ashley, Senman Balimkiz, Szczepanik Marian, Telenti Amalio, Askenase Philip W, Compans Richard W, von Andrian Ulrich H (2010), Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses., in Nature immunology, 11(12), 1127-35.
Host genetics and HIV-1: the final phase?
Fellay Jacques, Shianna Kevin V, Telenti Amalio, Goldstein David B (2010), Host genetics and HIV-1: the final phase?, in PLoS pathogens, 6(10), 1001033-1001033.
Phylogenetic approach reveals that virus genotype largely determines HIV set-point viral load.
Alizon Samuel, von Wyl Viktor, Stadler Tanja, Kouyos Roger D, Yerly Sabine, Hirschel Bernard, Böni Jürg, Shah Cyril, Klimkait Thomas, Furrer Hansjakob, Rauch Andri, Vernazza Pietro L, Bernasconi Enos, Battegay Manuel, Bürgisser Philippe, Telenti Amalio, Günthard Huldrych F, Bonhoeffer Sebastian, Swiss HIV Cohort Study (2010), Phylogenetic approach reveals that virus genotype largely determines HIV set-point viral load., in PLoS pathogens, 6(9), 1001123-1001123.
The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.
International HIV Controllers Study, Pereyra Florencia, Jia Xiaoming, McLaren Paul J, Telenti Amalio, de Bakker Paul I W, Walker Bruce D, Ripke Stephan, Brumme Chanson J, Pulit Sara L, Carrington Mary, Kadie Carl M, Carlson Jonathan M, Heckerman David, Graham Robert R, Plenge Robert M, Deeks Steven G, Gianniny Lauren, Crawford Gabriel, Sullivan Jordan, Gonzalez Elena, Davies Leela, Camargo Amy, Moore Jamie M, Beattie Nicole (2010), The major genetic determinants of HIV-1 control affect HLA class I peptide presentation., in Science (New York, N.Y.), 330(6010), 1551-7.

Patents

Title Date Number Inventor Owner
Privacy enhancing technologies for medical tests using genomic data 01.01.2013 12184372-2201

Associated projects

Number Title Start Funding scheme
149724 Novel mechanisms of HIV control in the infected cell 01.12.2013 Project funding
130699 24 hours in the life of HIV-1 01.04.2010 Project funding
141234 Pharmacologie clinique et pharmacogénétique de la prise en charge complexe des sujets infectés par HIV ou co-infectés par HIV et HCV 01.04.2012 Project funding (special)
148522 Swiss HIV Cohort Study (SHCS) 01.01.2014 Cohort Studies Large
147665 Defining a repertoire of innate immunity genes contributing to intracellular defense against pathogens 01.08.2013 Sinergia
110012 Host genetic and genomic determinants of susceptibility to HIV-1 01.11.2005 Project funding

Abstract

Exogenous infection by retroviruses has occurred repeatedly during the evolution of mammals, as evidenced by the genome “fossil” record. Up to 8% of the human genome is of proviral origin. The extent of pressure has led to prominent signs of positive selection in the primate genome. A number of genes of the innate immunity are dedicated to the control of retroelements and retroviruses, and bear some of the strongest signals of positive Darwinian forces found in the human genome. Mapping the positive selection pressures can be highly informative for the understanding of susceptibility to zoonotic transfers, for the mechanisms of control of retroviral activity, and possibly for the understanding of contemporary susceptibility in humans, or of differences in susceptibility across humans. To advance in this understanding the current proposal aims at:•Mapping signals of long-range positive selective pressure in primates, genome-wide.•Using genome-wide association study datasets to propose regions under recent positive selective pressure in the human population.•Studying these signals in the context of experimental retroviral infection.•Re-sequencing of candidate genes, selected on the basis of the evolutionary analyses, in individuals presenting distinct profiles of susceptibility to HIV.•Exploiting the tools of evolutionary genetics to re-construct ancestral proteins to be tested in functional assays against contemporary and ancestral retroviruses. Thus, this project extends the goals of previous research, and exploits prior results, tools and datasets created in the frame of Swiss National Science Foundation projects. The current research may lead to better understanding of susceptibility to HIV and other retroviruses, and constitutes a model for the study of other major human pathogens.
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