Nef Neutralizes the Ability of Exosomes from CD4+ T Cells to Act as Decoys during HIV-1 Infection

作者: Julianne V. de Carvalho , Rodrigo O. de Castro , Elaine Z. M. da Silva , Paola P. Silveira , Mara E. da Silva-Januário

DOI: 10.1371/JOURNAL.PONE.0113691

关键词:

摘要: Nef is an HIV-1 accessory protein that promotes viral replication and pathogenesis. A key function of to ensure sustained depletion CD4 MHC-I molecules in infected cells by inducing targeting these proteins multivesicular bodies (MVBs), ultimately lysosomes for degradation. also affects cellular secretory routes promoting its own secretion via exosomes. To better understand the effects on exocytic pathway, we investigated whether this factor modifies composition exosomes released T lymphocytes. We showed both are secreted from expression reduces amount investigate functional role novel activity Nef, performed vitro infection assays presence distinct populations demonstrated CD4+ cells, but not CD4− efficiently inhibit vitro. Because main receptor infection, results suggest displayed surface can bind envelope hindering virus interaction with target infection. Importantly, CD4-depleted expressing have a reduced capacity These provide evidence reducing besides original levels at cell surface.

参考文章(75)
Jeremiah F. Roeth, Maya Williams, Matthew R. Kasper, Tracey M. Filzen, Kathleen L. Collins, HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail. Journal of Cell Biology. ,vol. 167, pp. 903- 913 ,(2004) , 10.1083/JCB.200407031
Nienke B. Lubben, Daniela A. Sahlender, Alison M. Motley, Paul J. Lehner, Philippe Benaroch, Margaret S. Robinson, HIV-1 Nef-induced Down-Regulation of MHC Class I Requires AP-1 and Clathrin but Not PACS-1 and Is Impeded by AP-2 Molecular Biology of the Cell. ,vol. 18, pp. 3351- 3365 ,(2007) , 10.1091/MBC.E07-03-0218
Gregory B Melikyan, HIV entry: a game of hide-and-fuse? Current Opinion in Virology. ,vol. 4, pp. 1- 7 ,(2014) , 10.1016/J.COVIRO.2013.09.004
Jeffrey S. Schorey, Sanchita Bhatnagar, Exosome Function: From Tumor Immunology to Pathogen Biology Traffic. ,vol. 9, pp. 871- 881 ,(2008) , 10.1111/J.1600-0854.2008.00734.X
Harry W. Kestier, Douglas J. Ringler, Kazuyasu Mori, Dennis L. Panicali, Prabhat K. Sehgal, Muthiah D. Daniel, Ronald C. Desrosiers, Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. ,vol. 65, pp. 651- 662 ,(1991) , 10.1016/0092-8674(91)90097-I
J. A. Leonard, T. Filzen, C. C. Carter, M. Schaefer, K. L. Collins, HIV-1 Nef Disrupts Intracellular Trafficking of Major Histocompatibility Complex Class I, CD4, CD8, and CD28 by Distinct Pathways That Share Common Elements Journal of Virology. ,vol. 85, pp. 6867- 6881 ,(2011) , 10.1128/JVI.00229-11
Chien-Hui Hung, Laurel Thomas, Carl E. Ruby, Katelyn M. Atkins, Nicholas P. Morris, Zachary A. Knight, Isabel Scholz, Eric Barklis, Andrew D. Weinberg, Kevan M. Shokat, Gary Thomas, HIV-1 Nef Assembles a Src Family Kinase-ZAP-70/Syk-PI3K Cascade to Downregulate Cell-Surface MHC-I Cell Host & Microbe. ,vol. 1, pp. 121- 133 ,(2007) , 10.1016/J.CHOM.2007.03.004
Kaushik Choudhuri, Jaime Llodrá, Eric W Roth, Jones Tsai, Susana Gordo, Kai W Wucherpfennig, Lance C Kam, David L Stokes, Michael L Dustin, None, Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse Nature. ,vol. 507, pp. 118- 123 ,(2014) , 10.1038/NATURE12951
T Folks, D. Powell, M. Lightfoote, S Benn, M. Martin, A. Fauci, Induction of HTLV-III/LAV from a nonvirus-producing T-cell line: implications for latency Science. ,vol. 231, pp. 600- 602 ,(1986) , 10.1126/SCIENCE.3003906
N. J. Deacon, A. Tsykin, A. Solomon, K. Smith, M. Ludford-Menting, A. Ellett, D. J. Hooker, D. A. McPhee, A. L. Greenway, C. Chatfield, V. A. Lawson, S. Crowe, A. Maerz, S. Sonza, J. Learmont, J. S. Sullivan, A. Cunningham, D. Dwyer, D. Dowton, J. Mills, Genomic Structure of an Attenuated Quasi Species of HIV-1 from a Blood Transfusion Donor and Recipients Science. ,vol. 270, pp. 988- 991 ,(1995) , 10.1126/SCIENCE.270.5238.988