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Functional characterization of HIV-1 Nef mutants in the context of viral infection by Oliver T. Fackler; Arnaud Moris; Nadine Tibroni; Simone I. Giese; Bärbel Glass; Olivier Schwartz; Hans-Georg Kräusslich is a Medicine article available to read on EtoBox.

What is Functional characterization of HIV-1 Nef mutants in the context of viral infection about?

Nef is an important pathogenesis factor of HIV-1 with a multitude of effector functions. We have designed a broad panel of isogenic viruses encoding defined mutants of HIV-1 SF2 Nef and analyzed their biological activity in the context of productive HIV-1 infection. Analysis of subcellular localization, virion incorporation, downregulation of cell surface CD4 and MHC-I, enhancement of virion infectivity and facilitation of HIV replication in primary human T lymphocytes mostly confirmed the mapping of Nef determinants previously reported upon isolated expression of Nef. However, reduced activity in downregulation of CD4, infectivity enhancement and virion incorporation of a Nef variant (Δ12-39) lacking an amphipatic helix required for binding of a cellular kinase complex and the association of Nef with MHC-I/AP-1 suggested a novel role of this N-terminal motif. The SH3 binding motif of Nef was partially required for infectivity enhancement and replication but not for receptor downmodulation. In contrast to previous results obtained using other Nef alleles, non-myristoylated SF2-Nef was only partly defective when expressed during HIV infection and was present in HIV-1 particles. Impo

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Author

Oliver T. Fackler; Arnaud Moris; Nadine Tibroni; Simone I. Giese; Bärbel Glass; Olivier Schwartz; Hans-Georg Kräusslich

Publisher

Elsevier BV

Published

2006

Language

EN

Field

Medicine (Life Sciences)