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Koppensteiner, H.* ; Höhne, K. ; Gondim, M.V. ; Gobert, F.-X.* ; Widder, M.* ; Gundlach, S.* ; Heigele, A.* ; Kirchhoff, F.* ; Winkler, M.* ; Benaroch, P.* ; Schindler, M.

Lentiviral Nef suppresses iron uptake in a strain specific manner through inhibition of Transferrin endocytosis.

Retrovirol. 11:1 (2014)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Increased cellular iron levels are associated with high mortality in HIV-1 infection. Moreover iron is an important cofactor for viral replication, raising the question whether highly divergent lentiviruses actively modulate iron homeostasis. Here, we evaluated the effect on cellular iron uptake upon expression of the accessory protein Nef from different lentiviral strains. RESULTS: Surface Transferrin receptor (TfR) levels are unaffected by Nef proteins of HIV-1 and its simian precursors but elevated in cells expressing Nefs from most other primate lentiviruses due to reduced TfR internalization. The SIV Nef-mediated reduction of TfR endocytosis is dependent on an N-terminal AP2 binding motif that is not required for downmodulation of CD4, CD28, CD3 or MHCI. Importantly, SIV Nef-induced inhibition of TfR endocytosis leads to the reduction of Transferrin uptake and intracellular iron concentration and is accompanied by attenuated lentiviral replication in macrophages. CONCLUSION: Inhibition of Transferrin and thereby iron uptake by SIV Nef might limit viral replication in myeloid cells. Furthermore, this new SIV Nef function could represent a virus-host adaptation that evolved in natural SIV-infected monkeys.  
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Publication type Article: Journal article
Document type Scientific Article
Keywords HIV; SIV; Nef; Iron homeostasis; AIDS; Lentiviral replication; Macrophages; Virus Type-1 Nef; Cell-surface Expression; Complex Class-ii; Hiv-infection; Invariant Chain; Thalassemic Patients; Clathrin Adapter; Down-modulation; Serum Ferritin; Mortality
e-ISSN 1742-4690
Journal Retrovirology
Quellenangaben Volume: 11, Issue: 1 Pages: , Article Number: 1 Supplement: ,
Publisher Biomed Central Ltd
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)