Lack of endogenous TRIM5alpha-mediated restriction in rhesus macaque dendritic cells.

Nathalie J Arhel (1) , Sébastien Nisole (2) , Laetitia Carthagena (2) , Frédéric Coutant (1) , Philippe Souque (1) , Audrey Brussel (3) , Jérôme Estaquier (3) , Pierre Charneau (1)

1 Virologie moléculaire et Vectorologie
2 [Institut Cochin] Departement Infection, immunité, inflammation
3 Physiopathologie des Infections Lentivirales

Rhesus macaques are resistant to infection by HIV-1 as a result of an innate cellular restriction mechanism attributable to the expression of rhTRIM5alpha, a member of the large tripartite motif (TRIM) protein family. TRIM5alpha-mediated restriction, which occurs before reverse transcription through targeting of the HIV-1 capsid, has been identified in a number of macaque primary cells and cell lines and is thought to occur in all macaque cell types. We report, however, that rhesus macaque dendritic cells (DCs) lack TRIM5alpha-mediated restriction and are equally permissive to HIV-1 infection as human DCs. Evidence suggests that, although TRIM5alpha RNA levels are normal in these cells, the protein may be dysfunctional. We propose that abrogation of TRIM5alpha-mediated restriction in DCs, although still operative in cells that replicate HIV-1 (macrophages, T lymphocytes), illustrates the need for innate mechanisms to not inhibit adaptive immune responses to ensure an optimal fight against pathogens.

Domaines: Microbiologie et Parasitologie

Nathalie J Arhel, Sébastien Nisole, Laetitia Carthagena, Frédéric Coutant, Philippe Souque, et al.. Lack of endogenous TRIM5alpha-mediated restriction in rhesus macaque dendritic cells.. Blood, 2008, 112 (9), pp.3772-6. ⟨10.1182/blood-2008-04-151761⟩. ⟨pasteur-00457787⟩