HIV-1 nef triggers macrophage fusion in a p61Hck- and protease-dependent manner

Journal of Immunology

Volumn 184, Issue 12, 2010, Pages 7030-7039

  Vérollet, Christel ^a,b   Zhang, Yan Mei ^a,b   Cabec, Véronique Le ^a,b   Mazzolini, Julie ^c,d   Charrière, Guillaume ^a,b   Labrousse, Arnaud ^a,b   Bouchet, Jérôme ^c,d   Medina, Indira ^e   Biessen, Erik ^e   Niedergang, Florence ^c,d   Bénichou, Serge ^c,d   Maridonneau Parini, Isabelle ^a,b  

^a INSTITUT DE PHARMACOLOGIE ET DE BIOLOGIE STRUCTURALE   (France)

^b UNIVERSITÉ PAUL SABATIER   (France)

^c INSTITUT COCHIN   (France)

^d INSERM   (France)

^e MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE; HEMATOPOIETIC CELL KINASE; ISOPROTEIN; NEF PROTEIN; PROTEIN 61 HEMATOPOIETIC CELL KINASE; PROTEINASE; UNCLASSIFIED DRUG; ISOENZYME;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ARTICLE; CONTROLLED STUDY; CYTOSOL; GENE DELETION; GIANT CELL; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; LYSOSOME; MACROPHAGE; MYRISTYLATION; NONHUMAN; PHAGOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; ANIMAL; CELL LINE; FLUORESCENCE MICROSCOPY; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOBLOTTING; IMMUNOLOGY; METABOLISM; MOUSE; VIROLOGY;

ANIMALS; CELL LINE; GENE PRODUCTS, NEF; GIANT CELLS; HIV INFECTIONS; HUMANS; IMMUNOBLOTTING; ISOENZYMES; MACROPHAGES; MICE; MICROSCOPY, FLUORESCENCE; PROTO-ONCOGENE PROTEINS C-HCK;

EID: 77953647799     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0903345     Document Type: Article

References (91)

1. Stevenson, M. 2003. HIV-1 pathogenesis. Nat. Med. 9: 853-860.
2. Carter, C. A., and L. S. Ehrlich. 2008. Cell biology of HIV-1 infection of macrophages. Annu. Rev. Microbiol. 62: 425-443.
3. Wahl, S. M., T. Greenwell-Wild, and N. Vázquez. 2006. HIV accomplices and adversaries in macrophage infection. J. Leukoc. Biol. 80: 973-983.
4. Hütter, G., D. Nowak, M. Mossner, S. Ganepola, A. Müssig, K. Allers, T. Schneider, J. Hofmann, C. Kücherer, O. Blau, et al. 2009. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N. Engl. J. Med. 360: 692-698.
5. Crowe, S., T. Zhu, and W. A. Muller. 2003. The contribution of monocyte infection and trafficking to viral persistence, and maintenance of the viral reservoir in HIV infection. J. Leukoc. Biol. 74: 635-641.
6. Gendelman, H. E., J. M. Orenstein, M. A. Martin, C. Ferrua, R. Mitra, T. Phipps, L. A. Wahl, H. C. Lane, A. S. Fauci, D. S. Burke, et al. 1988. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J. Exp. Med. 167: 1428-1441.
7. Orenstein, J. M. 2001. The macrophage in HIV infection. Immunobiology 204: 598-602.
8. Dargent, J. L., L. Lespagnard, A. Kornreich, P. Hermans, N. Clumeck, and A. Verhest. 2000. HIV-associated multinucleated giant cells in lymphoid tissue of the Waldeyer's ring: a detailed study. Mod. Pathol. 13: 1293-1299.
9. Lewin-Smith, M., S. M. Wahl, and J. M. Orenstein. 1999. Human immunodeficiency virus-rich multinucleated giant cells in the colon: a case report with transmission electron microscopy, immunohistochemistry, and in situ hybridization. Mod. Pathol. 12: 75-81.
10. Nardacci, R., A. Antinori, G. Kroemer, and M. Piacentini. 2005. Cell death mechanisms in HIV-associated dementia: the involvement of syncytia. Cell Death Differ. 12(Suppl 1): 855-858. (Pubitemid 41030601)
11. Kadiu, I., M. Ricardo-Dukelow, P. Ciborowski, and H. E. Gendelman. 2007. Cytoskeletal protein transformation in HIV-1-infected macrophage giant cells. J. Immunol. 178: 6404-6415.
12. Anderson, J. M. 2000. Multinucleated giant cells. Curr. Opin. Hematol. 7: 40-47.
13. Kestler, H. W., 3rd, D. J. Ringler, K. Mori, D. L. Panicali, P. K. Sehgal, M. D. Daniel, and R. C. Desrosiers. 1991. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 65: 651-662.
14. Kirchhoff, F., T. C. Greenough, D. B. Brettler, J. L. Sullivan, and R. C. Desrosiers. 1995. Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N. Engl. J. Med. 332: 228-232.
15. Gorry, P. R., D. A. McPhee, E. Verity, W. B. Dyer, S. L. Wesselingh, J. Learmont, J. S. Sullivan, M. Roche, J. J. Zaunders, D. Gabuzda, et al. 2007. Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo. Retrovirology 4: 66-97.
16. Roeth, J. F., and K. L. Collins. 2006. Human immunodeficiency virus type 1 Nef: adapting to intracellular trafficking pathways. Microbiol. Mol. Biol. Rev. 70: 548-563.
17. Kirchhoff, F., M. Schindler, A. Specht, N. Arhel, and J. Münch. 2008. Role of Nef in primate lentiviral immunopathogenesis. Cell. Mol. Life Sci. 65: 2621-2636.
18. Foster, J. L., and J. V. Garcia. 2008. HIV-1 Nef: at the crossroads. Retrovirology 5: 84-94.
19. Hanna, Z., D. G. Kay, N. Rebai, A. Guimond, S. Jothy, and P. Jolicoeur. 1998. Nef harbors a major determinant of pathogenicity for an AIDS-like disease induced by HIV-1 in transgenic mice. Cell 95: 163-175. (Pubitemid 28473778)
20. Hanna, Z., X. Weng, D. G. Kay, J. Poudrier, C. Lowell, and P. Jolicoeur. 2001. The pathogenicity of human immunodeficiency virus (HIV) type 1 Nef in CD4C/HIV transgenic mice is abolished by mutation of its SH3-binding domain, and disease development is delayed in the absence of Hck. J. Virol. 75: 9378-9392. (Pubitemid 32851942)
21. Lee, C. H., B. Leung, M. A. Lemmon, J. Zheng, D. Cowburn, J. Kuriyan, and K. Saksela. 1995. A single amino acid in the SH3 domain of Hck determines its high affinity and specificity in binding to HIV-1 Nef protein. EMBO J. 14: 5006-5015.
22. Stangler, T., T. Tran, S. Hoffmann, H. Schmidt, E. Jonas, and D. Willbold. 2007. Competitive displacement of full-length HIV-1 Nef from the Hck SH3 domain by a high-affinity artificial peptide. Biol. Chem. 388: 611-615.
23. Moarefi, I., M. LaFevre-Bernt, F. Sicheri, M. Huse, C. H. Lee, J. Kuriyan, and W. T. Miller. 1997. Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement. Nature 385: 650-653.
24. Hiyoshi, M., S. Suzu, Y. Yoshidomi, R. Hassan, H. Harada, N. Sakashita, H. Akari, K. Motoyoshi, and S. Okada. 2008. Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor. Blood 111: 243-250.
25. Suzu, S., H. Harada, T. Matsumoto, and S. Okada. 2005. HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and inhibits M-CSF bioactivities. Blood 105: 3230-3237.
26. Briggs, S. D., B. Scholtz, J. M. Jacque, S. Swingler, M. Stevenson, and T. E. Smithgall. 2001. HIV-1 Nef promotes survival of myeloid cells by a Stat3- dependent pathway. J. Biol. Chem. 276: 25605-25611.
27. Trible, R. P., L. Emert-Sedlak, T. E. Wales, V. Ayyavoo, J. R. Engen, and T. E. Smithgall. 2007. Allosteric loss-of-function mutations in HIV-1 Nef from a long-term non-progressor. J. Mol. Biol. 374: 121-129.
28. Lock, P., S. Ralph, E. Stanley, I. Boulet, R. Ramsay, and A. R. Dunn. 1991. Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization. Mol. Cell. Biol. 11: 4363-4370.
29. Guiet, R., R. Poincloux, J. Castandet, L. Marois, A. Labrousse, V. Le Cabec, and I. Maridonneau-Parini. 2008. Hematopoietic cell kinase (Hck) isoforms and phagocyte duties - from signaling and actin reorganization to migration and phagocytosis. Eur. J. Cell Biol. 87: 527-542.
30. Cougoule, C., S. Carréno, J. Castandet, A. Labrousse, C. Astarie-Dequeker, R. Poincloux, V. Le Cabec, and I. Maridonneau-Parini. 2005. Activation of the lysosome-associated p61Hck isoform triggers the biogenesis of podosomes. Traffic 6: 682-694. (Pubitemid 40959695)
31. Carréno, S., M. E. Gouze, S. Schaak, L. J. Emorine, and I. Maridonneau-Parini. 2000. Lack of palmitoylation redirects p59Hck from the plasma membrane to p61Hck-positive lysosomes. J. Biol. Chem. 275: 36223-36229.
32. Astarie-Dequeker, C., S. Carreno, C. Cougoule, and I. Maridonneau-Parini. 2002. The protein tyrosine kinase Hck is located on lysosomal vesicles that are physically and functionally distinct from CD63-positive lysosomes in human macrophages. J. Cell Sci. 115: 81-89. (Pubitemid 34105531)
33. Komuro, I., Y. Yokota, S. Yasuda, A. Iwamoto, and K. S. Kagawa. 2003. CSF-induced and HIV-1-mediated distinct regulation of Hck and C/EBPbeta represent a heterogeneous susceptibility of monocyte-derived macrophages to M-tropic HIV-1 infection. J. Exp. Med. 198: 443-453.
34. Tokunaga, K., E. Kiyokawa, M. Nakaya, N. Otsuka, A. Kojima, T. Kurata, and M. Matsuda. 1998. Inhibition of human immunodeficiency virus type 1 virion entry by dominant-negative Hck. J. Virol. 72: 6257-6259. (Pubitemid 28283427)
35. Komuro, I., T. Sunazuka, K. S. Akagawa, Y. Yokota, A. Iwamoto, and S. Omura. 2008. Erythromycin derivatives inhibit HIV-1 replication in macrophages through modulation of MAPK activity to induce small isoforms of C/EBPbeta. Proc. Natl. Acad. Sci. USA 105: 12509-12514.
36. Burtey, A., J. Z. Rappoport, J. Bouchet, S. Basmaciogullari, J. Guatelli, S. M. Simon, S. Benichou, and A. Benmerah. 2007. Dynamic interaction of HIV-1 Nef with the clathrin-mediated endocytic pathway at the plasma membrane. Traffic 8: 61-76. (Pubitemid 44921883)
37. Madrid, R., K. Janvier, D. Hitchin, J. Day, S. Coleman, C. Noviello, J. Bouchet, A. Benmerah, J. Guatelli, and S. Benichou. 2005. Nef-induced alteration of the early/recycling endosomal compartment correlates with enhancement of HIV-1 infectivity. J. Biol. Chem. 280: 5032-5044.
38. Greenberg, M. E., A. J. Iafrate, and J. Skowronski. 1998. The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes. EMBO J. 17: 2777-2789.
39. Rauch, S., K. Pulkkinen, K. Saksela, and O. T. Fackler. 2008. Human immunodeficiency virus type 1 Nef recruits the guanine exchange factor Vav1 via an unexpected interface into plasma membrane microdomains for association with p21-activated kinase 2 activity. J. Virol. 82: 2918-2929.
40. Laguette, N., C. Brégnard, J. Bouchet, A. Benmerah, S. Benichou, and S. Basmaciogullari. 2009. Nef-induced CD4 endocytosis in human immunodeficiency virus type 1 host cells: role of p56lck kinase. J. Virol. 83: 7117-7128.
41. Carréno, S., E. Caron, C. Cougoule, L. J. Emorine, and I. Maridonneau-Parini. 2002. p59Hck isoform induces F-actin reorganization to form protrusions of the plasma membrane in a Cdc42- and Rac-dependent manner. J. Biol. Chem. 277: 21007-21016.
42. Klemsz, M. J., S. R. McKercher, and R. A. Maki. 1987. Nucleotide sequence of the mouse hck gene. Nucleic Acids Res. 15: 9600.
43. Astarie-Dequeker, C., E. N. N'Diaye, V. Le Cabec, M. G. Rittig, J. Prandi, and I. Maridonneau-Parini. 1999. The mannose receptor mediates uptake of pathogenic and nonpathogenic mycobacteria and bypasses bactericidal responses in human macrophages. Infect. Immun. 67: 469-477.
44. Clavel, F., M. Guyader, D. Guétard, M. Sallé, L. Montagnier, and M. Alizon. 1986. Molecular cloning and polymorphism of the human immune deficiency virus type 2. Nature 324: 691-695. (Pubitemid 17206364)
45. Laguette, N., S. Benichou, and S. Basmaciogullari. 2009. Human immunodeficiency virus type 1 Nef incorporation into virions does not increase infectivity. J. Virol. 83: 1093-1104.
46. Villeneuve, C., M. Gilleron, I. Maridonneau-Parini, M. Daffé, C. Astarie- Dequeker, and G. Etienne. 2005. Mycobacteria use their surface-exposed glycolipids to infect human macrophages through a receptor-dependent process. J. Lipid Res. 46: 475-483. (Pubitemid 43109784)
47. Welch, H., and I. Maridonneau-Parini. 1997. Hck is activated by opsonized zymosan and A23187 in distinct subcellular fractions of human granulocytes. J. Biol. Chem. 272: 102-109.
48. Helming, L., E. Tomasello, T. R. Kyriakides, F. O. Martinez, T. Takai, S. Gordon, and E. Vivier. 2008. Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. Sci. Signal. 1: ra11.
49. Swingler, S., J. Zhou, C. Swingler, A. Dauphin, T. Greenough, P. Jolicoeur, and M. Stevenson. 2008. Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS. Cell Host Microbe 4: 63-76. (Pubitemid 351958115)
50. Saksela, K., G. Cheng, and D. Baltimore. 1995. Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4. EMBO J. 14: 484-491.
51. Thomas, S. M., and J. S. Brugge. 1997. Cellular functions regulated by Src family kinases. Annu. Rev. Cell Dev. Biol. 13: 513-609.
52. Briggs, S. D., E. C. Lerner, and T. E. Smithgall. 2000. Affinity of Src family kinase SH3 domains for HIV Nef in vitro does not predict kinase activation by Nef in vivo. Biochemistry 39: 489-495.
53. Helming, L., and S. Gordon. 2007. The molecular basis of macrophage fusion. Immunobiology 212: 785-793.
54. Trible, R. P., L. Emert-Sedlak, and T. E. Smithgall. 2006. HIV-1 Nef selectively activates Src family kinases Hck, Lyn, and c-Src through direct SH3 domain interaction. J. Biol. Chem. 281: 27029-27038.
55. Briggs, S. D., M. Sharkey, M. Stevenson, and T. E. Smithgall. 1997. SH3- mediated Hck tyrosine kinase activation and fibroblast transformation by the Nef protein of HIV-1. J. Biol. Chem. 272: 17899-17902.
56. Atkins, K. M., L. Thomas, R. T. Youker, M. J. Harriff, F. Pissani, H. You, and G. Thomas. 2008. HIV-1 Nef binds PACS-2 to assemble a multikinase cascade that triggers major histocompatibility complex class I (MHC-I) down-regulation: analysis using short interfering RNA and knock-out mice. J. Biol. Chem. 283: 11772-11784.
57. Hung, C. H., L. Thomas, C. E. Ruby, K. M. Atkins, N. P. Morris, Z. A. Knight, I. Scholz, E. Barklis, A. D. Weinberg, K. M. Shokat, and G. Thomas. 2007. HIV-1 Nef assembles a Src family kinase-ZAP-70/Syk-PI3K cascade to down-regulate cell-surface MHC-I. Cell Host Microbe 1: 121-133.
58. Hassan, R., S. Suzu, M. Hiyoshi, N. Takahashi-Makise, T. Ueno, T. Agatsuma, H. Akari, J. Komano, Y. Takebe, K. Motoyoshi, and S. Okada. 2009. Dys-regulated activation of a Src tyroine kinase Hck at the Golgi disturbs N-glycosylation of a cytokine receptor Fms. J. Cell. Physiol. 221: 458-468.
59. Lee, S. H., J. Rho, D. Jeong, J. Y. Sul, T. Kim, N. Kim, J. S. Kang, T. Miyamoto, T. Suda, S. K. Lee, et al. 2006. v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation. Nat. Med. 12: 1403-1409.
60. Ohtake, Y., H. Tojo, and M. Seiki. 2006. Multifunctional roles of MT1-MMP in myofiber formation and morphostatic maintenance of skeletal muscle. J. Cell Sci. 119: 3822-3832. (Pubitemid 44614434)
61. Gogos, J. A., R. Thompson, W. Lowry, B. F. Sloane, H. Weintraub, and M. Horwitz. 1996. Gene trapping in differentiating cell lines: regulation of the lysosomal protease cathepsin B in skeletal myoblast growth and fusion. J. Cell Biol. 134: 837-847.
62. Oshiro, T., Y. Shibasaki, T. J. Martin, and T. Sasaki. 2001. Immunolocalization of vacuolar-type H+-ATPase, cathepsin K, matrix metalloproteinase-9, and receptor activator of NFkappaB ligand in odontoclasts during physiological root resorption of human deciduous teeth. Anat. Rec. 264: 305-311.
63. Journet, A., A. Chapel, S. Kieffer, F. Roux, and J. Garin. 2002. Proteomic analysis of human lysosomes: application to monocytic and breast cancer cells. Proteomics 2: 1026-1040.
64. Callahan, J. W., R. D. Bagshaw, and D. J. Mahuran. 2008. The integral membrane of lysosomes: its proteins and their roles in disease. J. Proteomics 72: 23-33.
65. Mastrolorenzo, A., S. Rusconi, A. Scozzafava, G. Barbaro, and C. T. Supuran. 2007. Inhibitors of HIV-1 protease: current state of the art 10 years after their introduction. From antiretroviral drugs to antifungal, antibacterial and antitumor agents based on aspartic protease inhibitors. Curr. Med. Chem. 14: 2734-2748.
66. Lifson, J. D., M. B. Feinberg, G. R. Reyes, L. Rabin, B. Banapour, S. Chakrabarti, B. Moss, F. Wong-Staal, K. S. Steimer, and E. G. Engleman. 1986. Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature 323: 725-728.
67. Lifson, J. D., G. R. Reyes, M. S. McGrath, B. S. Stein, and E. G. Engleman. 1986. AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen. Science 232: 1123-1127.
68. Vignery, A. 2005. Macrophage fusion: the making of osteoclasts and giant cells. J. Exp. Med. 202: 337-340.
69. Vignery, A. 2008. Macrophage fusion: molecular mechanisms. Methods Mol. Biol. 475: 149-161.
70. Briand, G., B. Barbeau, J. Corbeil, and M. Tremblay. 1997. Enhancement of HIV-1-induced syncytium formation in T cells by the tyrosyl kinase p56lck. Virology 231: 10-19. (Pubitemid 27238756)
71. Hildreth, J. E., and R. J. Orentas. 1989. Involvement of a leukocyte adhesion receptor (LFA-1) in HIV-induced syncytium formation. Science 244: 1075-1078.
72. Barbeau, B., J. F. Fortin, N. Genois, and M. J. Tremblay. 1998. Modulation of human immunodeficiency virus type 1-induced syncytium formation by the conformational state of LFA-1 determined by a new luciferase-based syncytium quantitative assay. J. Virol. 72: 7125-7136.
73. Pantaleo, G., L. Butini, C. Graziosi, G. Poli, S. M. Schnittman, J. J. Greenhouse, J. I. Gallin, and A. S. Fauci. 1991. Human immunodeficiency virus (HIV) infection in CD4+ T lymphocytes genetically deficient in LFA-1: LFA-1 is required for HIV-mediated cell fusion but not for viral transmission. J. Exp. Med. 173: 511-514.
74. Valentin, A., K. Lundin, M. Patarroyo, and B. Asjö. 1990. The leukocyte adhesion glycoprotein CD18 participates in HIV-1-induced syncytia formation in monocytoid and T cells. J. Immunol. 144: 934-937. (Pubitemid 20065034)
75. Lifson, J., S. Coutré, E. Huang, and E. Engleman. 1986. Role of envelope glycoprotein carbohydrate in human immunodeficiency virus (HIV) infectivity and virus-induced cell fusion. J. Exp. Med. 164: 2101-2106.
76. Ranki, A., M. Nyberg, V. Ovod, M. Haltia, I. Elovaara, R. Raininko, H. Haapasalo, and K. Krohn. 1995. Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia. AIDS 9: 1001-1008.
77. Choi, H. J., and T. E. Smithgall. 2004. Conserved residues in the HIV-1 Nef hydrophobic pocket are essential for recruitment and activation of the Hck tyrosine kinase. J. Mol. Biol. 343: 1255-1268.
78. Greenway, A. L., H. Dutartre, K. Allen, D. A. McPhee, D. Olive, and Y. Collette. 1999. Simian immunodeficiency virus and human immunodeficiency virus type 1 nef proteins show distinct patterns and mechanisms of Src kinase activation. J. Virol. 73: 6152-6158.
79. Möhn, H., V. Le Cabec, S. Fischer, 61nd I. Maridonneau-Parini. 1995. The srcfamily protein-tyrosine kinase p59hck is located on the secretory granules in human neutrophils and translocates towards the phagosome during cell activation. Biochem. J. 309: 657-665.
80. Mócsai, A., Z. Jakus, T. Vántus, G. Berton, C. A. Lowell, and E. Ligeti. 2000. Kinase pathways in chemoattractant-induced degranulation of neutrophils: the role of p38 mitogen-activated protein kinase activated by Src family kinases. J. Immunol. 164: 4321-4331. (Pubitemid 30215095)
81. Vincent, C., I. Maridonneau-Parini, C. Le Clainche, P. Gounon, and A. Labrousse. 2007. Activation of p61Hck triggers WASp- and Arp2/3- dependent actin-comet tail biogenesis and accelerates lysosomes. J. Biol. Chem. 282: 19565-19574.
82. Hirahashi, J., D. Mekala, J. Van Ziffle, L. Xiao, S. Saffaripour, D. D. Wagner, S. D. Shapiro, C. Lowell, and T. N. Mayadas. 2006. Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Immunity 25: 271-283.
83. Gonzalo, P., M. C. Guadamillas, M. V. Hernández-Riquer, A. Pollán, A. Grande- García, R. A. Bartolomé, A. Vasanji, C. Ambrogio, R. Chiarle, J. Teixidó, et al. 2010. MT1-MMP is required for myeloid cell fusion via regulation of Rac1 signaling. Dev. Cell 18: 77-89.
84. Helming, L., and S. Gordon. 2009. Molecular mediators of macrophage fusion. Trends Cell Biol. 19: 514-522.
85. Colbert, J. D., S. P. Matthews, G. Miller, and C. Watts. 2009. Diverse regulatory roles for lysosomal proteases in the immune response. Eur. J. Immunol. 39: 2955-2965.
86. Ciborowski, P., I. Kadiu, W. Rozek, L. Smith, K. Bernhardt, M. Fladseth, M. Ricardo-Dukelow, and H. E. Gendelman. 2007. Investigating the human immunodeficiency virus type 1-infected monocyte-derived macrophage secretome. Virology 363: 198-209.
87. Sun-Wada, G. H., Y. Wada, and M. Futai. 2004. Diverse and essential roles of mammalian vacuolar-type proton pump ATPase: toward the physiological understanding of inside acidic compartments. Biochim. Biophys. Acta 1658: 106-114.
88. Thoulouze, M. I., N. Sol-Foulon, F. Blanchet, A. Dautry-Varsat, O. Schwartz, and A. Alcover. 2006. Human immunodeficiency virus type-1 infection impairs the formation of the immunological synapse. Immunity 24: 547-561. (Pubitemid 43728159)
89. Haller, C., S. Rauch, and O. T. Fackler. 2007. HIV-1 Nef employs two distinct mechanisms to modulate Lck subcellular localization and TCR induced actin remodeling. PLoS One 2: e1212.
90. Steain, M. C., B. Wang, and N. K. Saksena. 2008. The possible contribution of HIV-1-induced syncytia to the generation of intersubtype recombinants in vitro. AIDS 22: 1009-1017.
91. Orenstein, J. M., and S. M. Wahl. 1999. The macrophage origin of the HIV-expressing multinucleated giant cells in hyperplastic tonsils and adenoids. Ultrastruct. Pathol. 23: 79-91.