Insertion of Host-derived Costimulatory Molecules CD80 (B7.1) and CD86 (B7.2) into Human Immunodeficiency Virus Type 1 affects the Virus Life Cycle
Autor: | Michel J. Tremblay, Salim Bounou, Jean-François Giguère, Jean-Sébastien Paquette, Joaquín Madrenas |
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Rok vydání: | 2004 |
Předmět: |
CD28
CD3 Complex T-Lymphocytes Immunology chemical and pharmacologic phenomena Biology Virus Replication Microbiology Jurkat cells Virus Antigens CD3 Cell Line Jurkat Cells CD28 Antigens Viral life cycle Viral envelope CD80 Antigens CD Virology Antigens CD80 Humans CTLA-4 Antigen Antibody-dependent enhancement CD86 Antigens Immunology and Infectious Disease Host cell membrane Membrane Glycoproteins Antigens CD28 Macrophages NF-kappa B Virion hemic and immune systems Antigens CD86 CD3 Antigens Differentiation Virus-Cell Interactions Cell biology CD Insect Science Differentiation B7-1 Antigen HIV-1 B7-2 Antigen |
Zdroj: | Robarts Immunology and Transplantation Publications |
Popis: | Human immunodeficiency virus type 1 (HIV-1) carries virus-encoded and host-derived proteins. Recent advances in the functional characterization of host molecules inserted into mature virus particles have revealed that HIV-1 biology is influenced by the acquisition of host cell membrane components. The CD28/B7 receptor/ligand system is considered one of the fundamental elements of the normal immune response. Two major cell types that harbor HIV-1 in vivo, i.e., monocytes/macrophages and CD4 + T cells, express the costimulatory molecules CD80 (B7.1) and CD86 (B7.2). We investigated whether CD80 and CD86 are efficiently acquired by HIV-1, and if so, whether these host-encoded molecules can contribute to the virus life cycle. Here we provide the first evidence that the insertion of CD80 and CD86 into HIV-1 increases virus infectivity by facilitating the attachment and entry process due to interactions with their two natural ligands, CD28 and CTLA-4. Moreover, we demonstrate that NF-κB is induced by CD80- and CD86-bearing virions when they are combined with the engagement of the T-cell receptor/CD3 complex, an event that is inhibited upon surface expression of CTLA-4. Finally, both CD80 and CD86 were found to be efficiently incorporated into R5- and X4-tropic field strains of HIV-1 expanded in cytokine-treated macrophages. Thus, besides direct interactions between the virus envelope glycoproteins and cell surface constituents, such as CD4 and some specific chemokine coreceptors, HIV-1 may attach to target cells via interactions between cell-derived molecules incorporated into virions and their natural ligands. These findings support the theory that HIV-1-associated host proteins alter virus-host dynamics. |
Databáze: | OpenAIRE |
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