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HIV replication and pathogenesis

HIV replication and pathogenesis

Study of retroviruses has led to major advances in fundamental biology, most notably the discovery of oncogenes and the modification of the central dogma. In this spirit, we investigate mechanisms of HIV-1 replication and pathogenesis with the goal of advancing understanding of the basic workings of the cell. Through the development of genetic and biochemical screens we attempt to identify cellular factors of importance to HIV-1 and, more generally, to cell physiology.
In effect, we exploit HIV-1, using the virus to elucidate mechanisms of cell cycle progression and cytokinesis, signal transduction and cytokine expression, protein folding and degradation, as well as pathogen recognition and antigen presentation.
Our research is basic in nature but by shedding light on mechanisms of HIV-1 replication and immune system evasion we hope to contribute to the development of drugs and vaccines that target this virus.

Group's publications

Human cellular restriction factors that target HIV-1 replication.
BMC MEDICINE
2009 vol. 7 pp. 48-48
STREBEL K, LUBAN J, JEANG KT

The Double-stranded RNA Binding Domain of the Vaccinia Virus E3L Protein Inhibits Both RNA- and DNA-induced Activation of Interferon beta
JOURNAL OF BIOLOGICAL CHEMISTRY
2009 vol. 284(38) pp. 25471-25478
MARQ JB, HAUSMANN S, LUBAN J, KOLAKOFSKY D, GARCIN D

Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components
JOURNAL OF CLINICAL INVESTIGATION
2009 vol. 119(10) pp. 3035-3047
NEAGU MR, ZIEGLER P, PERTEL T, STRAMBIO-DE-CASTILLIA C, GRÜTTER C, MARTINETTI G, MAZZUCCHELLI L, GRÜTTER M, MANZ MG, LUBAN J

An Invariant Surface Patch on the TRIM5 alpha PRYSPRY Domain Is Required for Retroviral Restriction but Dispensable for Capsid Binding
JOURNAL OF VIROLOGY
2009 vol. 83(7) pp. 3365-3373
SEBASTIAN S, GRUTTER C, STRAMBIO DE CASTILLIA C, PERTEL T, OLIVARI S, GRUTTER MG, LUBAN J

Essential role of cyclophilin A for hepatitis C virus replication and virus production and possible link to polyprotein cleavage kinetics.
PLOS PATHOGENS
2009 vol. 5(8) pp. 1000546-1000546
KAUL A, STAUFFER S, BERGER C, PERTEL T, SCHMITT J, KALLIS S, ZAYAS M, LOHMANN V, LUBAN J, BARTENSCHLAGER R

HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation.
PLOS PATHOGENS
2009 vol. 5(9) pp. 1000574-1000574
MANGEAT B, GERS-HUBER G, LEHMANN M, ZUFFEREY M, LUBAN J, PIGUET V

Efficient IgM assembly and secretion require the plasma cell induced endoplasmic reticulum protein pERp1
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2009 vol. 106(40) pp. 17019-17024
VAN ANKEN E AND AL.

HIV-1 infection: going nuclear with TNPO3/Transportin-SR2 and integrase.
CURRENT BIOLOGY
2008 vol. 18(16) pp. 710-713
LUBAN J

A dual task for the Xbp1-responsive OS-9 variants in the mammalian endoplasmic reticulum: inhibiting secretion of misfolded protein conformers and enhancing their disposal.
JOURNAL OF BIOLOGICAL CHEMISTRY
2008 vol. 283(24) pp. 16446-16454
BERNASCONI R, PERTEL T, LUBAN J, MOLINARI M

Characterization of simian immunodeficiency virus SIVSM/human immunodeficiency virus type 2 Vpx function in human myeloid cells.
JOURNAL OF VIROLOGY
2008 vol. 82(24) pp. 12335-12345
GOUJON C, ARFI V, PERTEL T, LUBAN J, LIENARD J, RIGAL D, DARLIX JL, CIMARELLI A

Lentiviral vector gene transfer is limited by the proteasome at postentry steps in various types of stem cells.
STEM CELLS
2008 vol. 26(8) pp. 2142-2152
SANTONI DE SIO FR, CASCIO P, GRITTI A, NERI M, SAMPAOLESI M, GALLI C, LUBAN J, NALDINI L

The Retroviral Restriction Factor TRIM5alpha
CURRENT INFECTIOUS DISEASE REPORTS
2007 vol. 9(2) pp. 167-173
SEBASTIAN SARAH, LUBAN JEREMY

Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia
JOURNAL OF EXPERIMENTAL MEDICINE
2007 vol. 204(8) pp. 1741-1748
ZHU CHANGLIAN ET AL.

Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection
JOURNAL OF VIROLOGY
2007 vol. 81(3) pp. 1054-1061
LUBAN JEREMY

Vif counteracts a cyclophilin A-imposed inhibition of simian immunodeficiency viruses in human cells
JOURNAL OF VIROLOGY
2007 vol. 81(15) pp. 8080-8090
TAKEUCHI HIROAKI ET AL.

The role of lysine 186 in HIV-1 integrase multimerization
VIROLOGY
2007 vol. 364(1) pp. 227-236
BERTHOUX LIONEL, SEBASTIAN SARAH, MUESING MARK A., LUBAN JEREMY

Cyclophilin, TRIM5, and innate immunity to HIV-1
CURRENT OPINION IN MICROBIOLOGY
2006 vol. 9(4) pp. 404-408
SOKOLSKAJA ELENA, LUBAN JEREMY

Arsenic counteracts human immunodeficiency virus type 1 restriction by various TRIM5 orthologues in a cell type-dependent manner
JOURNAL OF VIROLOGY
2006 vol. 80(4) pp. 2051-2054
SEBASTIAN SARAH, SOKOLSKAJA ELENA, LUBAN JEREMY

Cyclophilin A and TRIM5alpha independently regulate human immunodeficiency virus type 1 infectivity in human cells
JOURNAL OF VIROLOGY
2006 vol. 80(6) pp. 2855-2862
SOKOLSKAJA E, BERTHOUX L, LUBAN J

G2 cell cycle arrest and cyclophilin A in lentiviral gene transfer
MOLECULAR THERAPY
2006 vol. 14(4) pp. 546-554
ZHANG SHANGMING, JOSEPH GUIANDRE, POLLOK KAREN, BERTHOUX LIONEL, SASTRY LAKSHMI, LUBAN JEREMY, KENNETH CORNETTA

Cyclophilin A-deficient mice are resistant to immunosuppression by cyclosporine
JOURNAL OF IMMUNOLOGY
2005 vol. 174(10) pp. 6030-6038
COLGAN J., ASMAL M., YU B., LUBAN J.

Cyclophilin A is required for TRIM5{alpha}-mediated resistance to HIV-1 in Old World monkey cells
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2005 vol. 102(41) pp. 14849-14853
BERTHOUX L., SEBASTIAN S., SOKOLSKAJA E., LUBAN J.

Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk
IMMUNITY
2004 vol. 21(2) pp. 189-201
COLGAN J., ASMAL M., YU B., SCHNEIDKRAUT J., LEE Y.-N., ANDREOTTI A., LUBAN J.

HIV-1 Vpr induces defects in mitosis, cytokinesis, nuclear structure, and centrosomes
MOLECULAR BIOLOGY OF THE CELL
2004 vol. 15(4) pp. 1793-1801
CHANG F., SEBASTIAN S., SAZER S, LUBAN J.

Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1
NATURE
2004 vol. 430(6999) pp. 569-573
SAYAH D., SOKOLSKAJA E., BERTHOUX E., LUBAN J.

Production of ribosome components in effector CD4+ T cells is accelerated by TCR stimulation and coordinated by ERK-MAPK
IMMUNITY
2003 vol. 19(4) pp. 535-548
ASMAL M, COLGAN J, NAEF F, YU B, MAGNASCO M, LUBAN J

Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors
NATURE MEDICINE
2003 vol. 9(9) pp. 1138-1143
TOWERS GJ, HATZIIOANNOU T, COWAN S, GOFF SP, LUBAN J, BIENIASZ PD

Cyclophilin A peptidyl-prolyl isomerase activity promotes ZPR1 nuclear export
MOLECULAR AND CELLULAR BIOLOGY : MCB
2002 vol. 22(20) pp. 6990-7003
ANSARI H., GRECO G., LUBAN J.

Research's domains




DATABASE-RESEARCH	GROUP OF BASIC RESEARCH

Jérémy LUBAN	Head of group CV	Research subject	Members of the group


	Links about the group Prof. J. Luban CMU / Dpt MIMOL Rue Michel-Servet 1 1211 Genève 4 Suisse Jeremy.Luban@unige.ch Tel.: +41 22 379 57 20 Group's web site / department Comments Pages updated the 17.11.2015		Reseach's subject \| Group's publications \| Research's domains HIV replication and pathogenesis HIV replication and pathogenesis Study of retroviruses has led to major advances in fundamental biology, most notably the discovery of oncogenes and the modification of the central dogma. In this spirit, we investigate mechanisms of HIV-1 replication and pathogenesis with the goal of advancing understanding of the basic workings of the cell. Through the development of genetic and biochemical screens we attempt to identify cellular factors of importance to HIV-1 and, more generally, to cell physiology. In effect, we exploit HIV-1, using the virus to elucidate mechanisms of cell cycle progression and cytokinesis, signal transduction and cytokine expression, protein folding and degradation, as well as pathogen recognition and antigen presentation. Our research is basic in nature but by shedding light on mechanisms of HIV-1 replication and immune system evasion we hope to contribute to the development of drugs and vaccines that target this virus. Group's publications Human cellular restriction factors that target HIV-1 replication. BMC MEDICINE 2009 vol. 7 pp. 48-48 STREBEL K, LUBAN J, JEANG KT The Double-stranded RNA Binding Domain of the Vaccinia Virus E3L Protein Inhibits Both RNA- and DNA-induced Activation of Interferon beta JOURNAL OF BIOLOGICAL CHEMISTRY 2009 vol. 284(38) pp. 25471-25478 MARQ JB, HAUSMANN S, LUBAN J, KOLAKOFSKY D, GARCIN D Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components JOURNAL OF CLINICAL INVESTIGATION 2009 vol. 119(10) pp. 3035-3047 NEAGU MR, ZIEGLER P, PERTEL T, STRAMBIO-DE-CASTILLIA C, GRÜTTER C, MARTINETTI G, MAZZUCCHELLI L, GRÜTTER M, MANZ MG, LUBAN J An Invariant Surface Patch on the TRIM5 alpha PRYSPRY Domain Is Required for Retroviral Restriction but Dispensable for Capsid Binding JOURNAL OF VIROLOGY 2009 vol. 83(7) pp. 3365-3373 SEBASTIAN S, GRUTTER C, STRAMBIO DE CASTILLIA C, PERTEL T, OLIVARI S, GRUTTER MG, LUBAN J Essential role of cyclophilin A for hepatitis C virus replication and virus production and possible link to polyprotein cleavage kinetics. PLOS PATHOGENS 2009 vol. 5(8) pp. 1000546-1000546 KAUL A, STAUFFER S, BERGER C, PERTEL T, SCHMITT J, KALLIS S, ZAYAS M, LOHMANN V, LUBAN J, BARTENSCHLAGER R HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLOS PATHOGENS 2009 vol. 5(9) pp. 1000574-1000574 MANGEAT B, GERS-HUBER G, LEHMANN M, ZUFFEREY M, LUBAN J, PIGUET V Efficient IgM assembly and secretion require the plasma cell induced endoplasmic reticulum protein pERp1 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2009 vol. 106(40) pp. 17019-17024 VAN ANKEN E AND AL. HIV-1 infection: going nuclear with TNPO3/Transportin-SR2 and integrase. CURRENT BIOLOGY 2008 vol. 18(16) pp. 710-713 LUBAN J A dual task for the Xbp1-responsive OS-9 variants in the mammalian endoplasmic reticulum: inhibiting secretion of misfolded protein conformers and enhancing their disposal. JOURNAL OF BIOLOGICAL CHEMISTRY 2008 vol. 283(24) pp. 16446-16454 BERNASCONI R, PERTEL T, LUBAN J, MOLINARI M Characterization of simian immunodeficiency virus SIVSM/human immunodeficiency virus type 2 Vpx function in human myeloid cells. JOURNAL OF VIROLOGY 2008 vol. 82(24) pp. 12335-12345 GOUJON C, ARFI V, PERTEL T, LUBAN J, LIENARD J, RIGAL D, DARLIX JL, CIMARELLI A Lentiviral vector gene transfer is limited by the proteasome at postentry steps in various types of stem cells. STEM CELLS 2008 vol. 26(8) pp. 2142-2152 SANTONI DE SIO FR, CASCIO P, GRITTI A, NERI M, SAMPAOLESI M, GALLI C, LUBAN J, NALDINI L The Retroviral Restriction Factor TRIM5alpha CURRENT INFECTIOUS DISEASE REPORTS 2007 vol. 9(2) pp. 167-173 SEBASTIAN SARAH, LUBAN JEREMY Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia JOURNAL OF EXPERIMENTAL MEDICINE 2007 vol. 204(8) pp. 1741-1748 ZHU CHANGLIAN ET AL. Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection JOURNAL OF VIROLOGY 2007 vol. 81(3) pp. 1054-1061 LUBAN JEREMY Vif counteracts a cyclophilin A-imposed inhibition of simian immunodeficiency viruses in human cells JOURNAL OF VIROLOGY 2007 vol. 81(15) pp. 8080-8090 TAKEUCHI HIROAKI ET AL. The role of lysine 186 in HIV-1 integrase multimerization VIROLOGY 2007 vol. 364(1) pp. 227-236 BERTHOUX LIONEL, SEBASTIAN SARAH, MUESING MARK A., LUBAN JEREMY Cyclophilin, TRIM5, and innate immunity to HIV-1 CURRENT OPINION IN MICROBIOLOGY 2006 vol. 9(4) pp. 404-408 SOKOLSKAJA ELENA, LUBAN JEREMY Arsenic counteracts human immunodeficiency virus type 1 restriction by various TRIM5 orthologues in a cell type-dependent manner JOURNAL OF VIROLOGY 2006 vol. 80(4) pp. 2051-2054 SEBASTIAN SARAH, SOKOLSKAJA ELENA, LUBAN JEREMY Cyclophilin A and TRIM5alpha independently regulate human immunodeficiency virus type 1 infectivity in human cells JOURNAL OF VIROLOGY 2006 vol. 80(6) pp. 2855-2862 SOKOLSKAJA E, BERTHOUX L, LUBAN J G2 cell cycle arrest and cyclophilin A in lentiviral gene transfer MOLECULAR THERAPY 2006 vol. 14(4) pp. 546-554 ZHANG SHANGMING, JOSEPH GUIANDRE, POLLOK KAREN, BERTHOUX LIONEL, SASTRY LAKSHMI, LUBAN JEREMY, KENNETH CORNETTA Cyclophilin A-deficient mice are resistant to immunosuppression by cyclosporine JOURNAL OF IMMUNOLOGY 2005 vol. 174(10) pp. 6030-6038 COLGAN J., ASMAL M., YU B., LUBAN J. Cyclophilin A is required for TRIM5{alpha}-mediated resistance to HIV-1 in Old World monkey cells PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2005 vol. 102(41) pp. 14849-14853 BERTHOUX L., SEBASTIAN S., SOKOLSKAJA E., LUBAN J. Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk IMMUNITY 2004 vol. 21(2) pp. 189-201 COLGAN J., ASMAL M., YU B., SCHNEIDKRAUT J., LEE Y.-N., ANDREOTTI A., LUBAN J. HIV-1 Vpr induces defects in mitosis, cytokinesis, nuclear structure, and centrosomes MOLECULAR BIOLOGY OF THE CELL 2004 vol. 15(4) pp. 1793-1801 CHANG F., SEBASTIAN S., SAZER S, LUBAN J. Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1 NATURE 2004 vol. 430(6999) pp. 569-573 SAYAH D., SOKOLSKAJA E., BERTHOUX E., LUBAN J. Production of ribosome components in effector CD4+ T cells is accelerated by TCR stimulation and coordinated by ERK-MAPK IMMUNITY 2003 vol. 19(4) pp. 535-548 ASMAL M, COLGAN J, NAEF F, YU B, MAGNASCO M, LUBAN J Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors NATURE MEDICINE 2003 vol. 9(9) pp. 1138-1143 TOWERS GJ, HATZIIOANNOU T, COWAN S, GOFF SP, LUBAN J, BIENIASZ PD Cyclophilin A peptidyl-prolyl isomerase activity promotes ZPR1 nuclear export MOLECULAR AND CELLULAR BIOLOGY : MCB 2002 vol. 22(20) pp. 6990-7003 ANSARI H., GRECO G., LUBAN J. Research's domains