Nef does not inhibit F-actin remodelling and HIV-1 cell-cell transmission at the T lymphocyte virological synapse

被引:22
作者
Haller, Claudia [1 ]
Tibroni, Nadine [1 ]
Rudolph, Jochen M. [1 ]
Grosse, Robert [2 ]
Fackler, Oliver T. [1 ]
机构
[1] Univ Heidelberg Hosp, Dept Infect Dis, D-69120 Heidelberg, Germany
[2] Univ Marburg, Inst Pharmacol, D-35032 Marburg, Germany
关键词
HIV-1 cell-cell spread; Nef; Virological synapse; T lymphocyte; Virion infectivity; F-actin polarization and remodelling; HUMAN-IMMUNODEFICIENCY-VIRUS; PATHOGENICITY FACTOR NEF; TISSUE EX-VIVO; DENDRITIC CELLS; TYPE-1; NEF; IMMUNOLOGICAL SYNAPSE; DC-SIGN; REPLICATION; SPREAD; INFECTIVITY;
D O I
10.1016/j.ejcb.2010.09.010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nef, a HIV-1 pathogenesis factor, elevates virus replication in vivo and thus progression to AIDS by incompletely defined mechanisms. As one of its biological properties. Nef enhances the infectivity of cell-free HIV-1 particles in single round infections, however it fails to provide a significant and amplifying growth advantage for HIV-1 on such virus producing cells. A major difference between HIV-1 cell-free single round infections and virus replication kinetics on T lymphocytes consists in the predominant role of cell-associated virus transmission rather than cell-free infection during multiple round virus replication. HIV-1 cell-to-cell transmission occurs across close cell contacts also referred to as virological synapse (VS) and involves polarization of the F-actin cytoskeleton, formation of F-actin rich membrane bridges as well as virus budding to cell cell contacts. Since Nef potently interferes with triggered actin remodelling in several cell systems to reduce e.g. cell motility and signal transduction, we set out here to address whether Nef also affects organization and possibly function of the T lymphocyte VS. We find that in addition to increasing infectivity of cell-free virions, Nef can also moderately enhance single rounds of HIV-1 cell cell transmission between Jurkat T lymphocytes. This occurs without affecting cell conjugation efficiencies or polarization of F-actin and HIV-1 p24Gag at the VS, identifying actin remodelling at the VS as an example of Nef-insensitive host cell actin rearrangements. However, Nef-mediated enhancement of single round cell-free infection or cell-to-cell transmission does not potentiate over multiple rounds of infection. These results suggest that Nef affects cell-free and cell-associated HIV-1 infection by the same mechanism acting on the intrinsic infectivity of HIV-1 particles. They further indicate that the high efficacy of cell-to-cell transmission can compensate such infectivity defects. Nef therefore selectively interferes with actin remodelling processes involved in antiviral host cell defense while actin driven processes that promote virus propagation remain unaltered. (C) 2010 Elsevier GmbH. All rights reserved.
引用
收藏
页码:913 / 921
页数:9
相关论文
共 57 条
[31]   Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo [J].
Michel, Nico ;
Goffinet, Christine ;
Ganter, Kerstin ;
Allespach, Ina ;
KewalRamani, Vineet N. ;
Saifuddin, Mohammed ;
Littman, Dan R. ;
Greene, Warner C. ;
Goldsmith, Mark A. ;
Keppler, Oliver T. .
RETROVIROLOGY, 2009, 6
[32]  
MOTHES W, 2010, J VIROL 0407
[33]   Nef-mediated enhancement of virion infectivity and stimulation of viral replication are fundamental properties of primate lentiviruses [J].
Muench, Jan ;
Rajan, Devi ;
Schindler, Michael ;
Specht, Anke ;
Ruecker, Elke ;
Novembre, Francis J. ;
Nerrienet, Eric ;
Mueller-Trutwin, Michaela C. ;
Peeters, Martine ;
Hahn, Beatrice H. ;
Kirchhoff, Frank .
JOURNAL OF VIROLOGY, 2007, 81 (24) :13852-13864
[34]   Construction and characterization of a fluorescently labeled infectious human immunodeficiency virus type 1 derivative [J].
Müller, B ;
Daecke, J ;
Fackler, OT ;
Dittmar, MT ;
Zentgraf, H ;
Kräusslich, HG .
JOURNAL OF VIROLOGY, 2004, 78 (19) :10803-10813
[35]   HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes [J].
Nobile, Cinzia ;
Rudnicka, Dominika ;
Hasan, Milena ;
Aulner, Nathalie ;
Porrot, Francoise ;
Machu, Christophe ;
Renaud, Olivier ;
Prevost, Marie-Christine ;
Hivroz, Claire ;
Schwartz, Olivier ;
Sol-Foulon, Nathalie .
JOURNAL OF VIROLOGY, 2010, 84 (05) :2282-2293
[36]   Nef is required for efficient HIV-1 replication in cocultures of dendritic cells and lymphocytes [J].
Petit, C ;
Buseyne, F ;
Boccaccio, C ;
Abastado, JP ;
Heard, JM ;
Schwartz, O .
VIROLOGY, 2001, 286 (01) :225-236
[37]   Dangerous liaisons at the virological synapse [J].
Piguet, V ;
Sattentau, Q .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (05) :605-610
[38]   Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef [J].
Pizzato, Massimo ;
Helander, Anna ;
Popova, Elena ;
Calistri, Arianna ;
Zamborlini, Alessia ;
Palu, Giorgio ;
Gottlinger, Heinrich G. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (16) :6812-6817
[39]   MLV glycosylated-Gag is an infectivity factor that rescues Nef-deficient HIV-1 [J].
Pizzato, Massimo .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (20) :9364-9369
[40]   Human immunodeficiency virus type 1 Nef: Adapting to intracellular trafficking pathways [J].
Roeth, Jeremiah F. ;
Collins, Kathleen L. .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2006, 70 (02) :548-+