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

Autor(es)

de Carvalho, Julianne V. ^[1] ; de Castro, Rodrigo O. ^[1] ; da Silva, Elaine Z. M. ^[1] ; Silveira, Paola P. ^[2] ; da Silva-Januario, Mara E. ^[1] ; Arruda, Eurico ^[1] ; Jamur, Maria C. ^[1] ; Oliver, Constance ^[1] ; Aguiar, Renato S. ^[2] ; daSilva, Luis L. P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, BR-14049 Ribeirao Preto - Brazil

^[2] Univ Fed Rio de Janeiro, Dept Genet, Mol Virol Lab, Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 9, n. 11 NOV 25 2014.
• Citações Web of Science: 20

Resumo

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

• Processo FAPESP: 09/50650-6 - Elucidação de mecanismos celulares e moleculares da modulação negativa de proteínas da superfície celular por NEF do HIV-1
• Beneficiário: Luis Lamberti Pinto da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores