A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells

Oliver T. Fackler, Dietlinde Wolf, H. Oliver Weber, Bernd Laffert, Paola D'Aloja, Beatrice Schuler-Thurner, Rebeca Geffin, Kalle Saksela, Matthias Geyer, B. Matija Peterlin, Gerold Schuler, Andreas S. Baur

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

In the infected host, the Nef protein of HIV/SIV is required for high viral loads and thus disease progression [1-3]. Recent evidence indicates that Nef enhances replication in the T cell compartment after the virus is transmitted from dendritic cells (DC) [4]. The underlying mechanism, however, is not clear. Here, we report that a natural variability in the proline-rich motif (R71T) profoundly modulated Nef-stimulated viral replication in primary T cells of immature dendritic cell/T cell cocultures. Whereas both Nef variants (R/T-Nef) downregulated CD4, only the isoform supporting viral replication (R-Nef) efficiently interacted with signaling molecules of the T cell receptor (TCR) environment and stimulated cellular activation. Structural analysis suggested that the R to T conversion induces conformational changes, altering the flexibility of the loop containing the PxxP motif and hence its ability to bind cellular partners. Our report suggests that functionally and conformationally distinct Nef isoforms modulate HIV replication on the interaction level with the TCR-signaling environment once the virus enters the T cell compartment.

Original languageEnglish (US)
Pages (from-to)1294-1299
Number of pages6
JournalCurrent Biology
Volume11
Issue number16
DOIs
StatePublished - Aug 21 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells'. Together they form a unique fingerprint.

  • Cite this

    Fackler, O. T., Wolf, D., Weber, H. O., Laffert, B., D'Aloja, P., Schuler-Thurner, B., Geffin, R., Saksela, K., Geyer, M., Peterlin, B. M., Schuler, G., & Baur, A. S. (2001). A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells. Current Biology, 11(16), 1294-1299. https://doi.org/10.1016/S0960-9822(01)00373-6