Antiretroviral restrition; HIV; zebrafish; primate SIV infection; Evolutionary genetics; primary cells
Rato Sylvie, Rausell Antonio, Muñoz Miguel, Telenti Amalio, Ciuffi Angela (2017), Single-cell analysis identifies cellular markers of the HIV permissive cell, in PLOS Pathogens
, 13(10), e1006678-e1006678.
Rausell Antonio, Muñoz Miguel, Martinez Raquel, Roger Thierry, Telenti Amalio, Ciuffi Angela (2016), Innate immune defects in HIV permissive cell lines, in Retrovirology
, 13(1), 43-43.
Krapp Christian, Hotter Dominik, Gawanbacht Ali, McLaren Paul J, Kluge Silvia F, Stürzel Christina M, Mack Katharina, Reith Elisabeth, Engelhart Susanne, Ciuffi Angela, Hornung Veit, Sauter Daniel, Telenti Amalio, Kirchhoff Frank (2016), Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity., in Cell host & microbe
, 19(4), 504-14.
Zirafi Onofrio, Kim Kyeong-Ae, Staendker Ludger, Mohr Katharina B., Sauter Daniel, Heigele Anke, Kluge Silvia F., Wiercinska Eliza, Chudziak Doreen, Richter Rudolf, Moepps Barbara, Gierschik Peter, Vas Virag, Geiger Hartmut, Lamla Markus, Weil Tanja, Burster Timo, Zgraja Andreas, Daubeuf Francois, Frossard Nelly, Hachet-Haas Muriel, Heunisch Fabian, Reichetzeder Christoph, Galzi Jean-Luc, Perez-Castells Javier (2015), Discovery and Characterization of an Endogenous CXCR4 Antagonist, in CELL REPORTS
, 11(5), 737-747.
Pyndiah Nitisha, Telenti Amalio, Rausell Antonio (2015), Evolutionary genomics and HIV restriction factors., in Current opinion in HIV and AIDS
, 10(2), 79-83.
Telenti Amalio (2015), Genomics of HIV infection., in Current opinion in HIV and AIDS
, 10(2), 77-8.
Pino Maria, Erkizia Itziar, Benet Susana, Erikson Elina, Fernández-Figueras Maria Teresa, Guerrero Dolores, Dalmau Judith, Ouchi Dan, Rausell Antonio, Ciuffi Angela, Keppler Oliver T, Telenti Amalio, Kräusslich Hans-Georg, Martinez-Picado Javier, Izquierdo-Useros Nuria (2015), HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells., in Retrovirology
, 12, 37-37.
McLaren Paul J, Gawanbacht Ali, Pyndiah Nitisha, Krapp Christian, Hotter Dominik, Kluge Silvia F, Götz Nicola, Heilmann Jessica, Mack Katharina, Sauter Daniel, Thompson Danielle, Perreaud Jérémie, Rausell Antonio, Munoz Miguel, Ciuffi Angela, Kirchhoff Frank, Telenti Amalio (2015), Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses., in Retrovirology
, 12, 41-41.
Julia Miguel, Telenti Amalio, Rausell Antonio (2015), Sincell: an R/Bioconductor package for statistical assessment of cell-state hierarchies from single-cell RNA-seq, in BIOINFORMATICS
, 31(20), 3377-3379.
Alcala Nicolas, Jensen Jeffrey D, Telenti Amalio, Vuilleumier Séverine (2015), The Genomic Signature of Population Reconnection Following Isolation: From Theory to HIV., in G3 (Bethesda, Md.)
, 6(1), 107-20.
Rausell Antonio, Telenti Amalio (2014), Genomics of host-pathogen interactions., in Sanger Ruth (ed.), Elsevier, United Kingdom, 32-8.
Bartha István, McLaren Paul J, Ciuffi Angela, Fellay Jacques, Telenti Amalio (2014), GuavaH: a compendium of host genomic data in HIV biology and disease., in Retrovirology
, 11, 6-6.
Telenti Amalio (2014), HIV: The mixed blessing of interferon., in Nature
, 511(7511), 537-8.
This proposal represents the continuation of the SNF grant “Host evolutionary genomics of HIV-1 and other retroviruses, 2010-2013”. It aims at understanding the cellular and antiviral function of genes that were identified through integrative genomic analyses that used evolutionary genetics, transcriptome and protein interaction data, and functional screens. Of 21389 human genes, 841 (4%) were identified because of features of positive selection in primates. In half of those genes we also detected evidence of codon-specific selection pressure. Among those genes, only 30 genes/proteins (0.14%) were identified through orthogonal datasets as being upregulated during HIV infection in vivo, and/or plausibly interacting with HIV proteins. When overexpressed, several of the 30 genes associated with a profound reduction of HIV replication in the cotransfected cell. siRNA led to the opposing phenotype for some genes that were constitutively transcribed. In addition to traditional components of the interferon response, we identified genes associated with apoptosis and immunomodulatory networks. Importantly, two genes strongly enhanced viral production.To advance in the understanding of cellular function and role in innate immunity of the identified genes, the current proposal aims to:•Explore the role of the candidate host genes in the regulation of the viral replication cycle. •Study the specificity of candidate host genes against HIV, by exploiting the use of primate orthologs and various lentiviral strains, and other retroviruses.•For confirmed anti(retro)viral genes, we aim at exploring a counteracting role of viral accessory proteins, and mapping the site of interaction of host and virus.•Extend analyses to primary cell systems.•Explore novel models of in vivo analysis of antiviral genes.Thus, this project fulfills the goals of previous research that served to identifying novel factors that limit viral replication; it exploits prior results, tools and datasets created in the framework of Swiss National Science Foundation projects. The current research may lead to better understanding of cellular defense against HIV and other retroviruses. The approach can serve as a model for the study of other major human pathogens.