1887

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Volume 86, Issue 6

Measles virus nucleoprotein induces cell-proliferation arrest and apoptosis through N–NR and N–FcRIIB1 interactions, respectively Free

Abstract

Measles virus (MV) nucleoprotein (N) is a cytosolic protein that is released into the extracellular compartment after apoptosis and/or secondary necrosis of MV-infected cells . Thus, MV-N becomes accessible to inhibitory cell-surface receptors: FcRIIB and an uncharacterized nucleoprotein receptor (NR). MV-N is composed of two domains: N (aa 1–400) and N (aa 401–525). To assess the contribution of MV-N domains and of these two receptors in suppression of cell proliferation, a human melanoma HT144 cell line expressing (HT144IIB1) or lacking FcRIIB1 was used as a model. Specific and exclusive N–FcRIIB1 and N–NR interactions were shown. Moreover, N binding to human NR predominantly led to suppression of cell proliferation by arresting cells in the G/G phases of the cell cycle, rather than to apoptosis. N binding to HT144IIB1 cells primarily triggered caspase-3 activation, in contrast to HT144IIB1/IC cells lacking the FcRIIB1 intra-cytoplasmic tail, thus demonstrating the specific inhibitory effect of the N–FcRIIB1 interaction. MV-N- and N-mediated apoptosis through FcRIIB1 was inhibited by the pan-caspase inhibitor zVAD-FMK, indicating that apoptosis was dependent on caspase activation. By using N deletion proteins, it was also shown that the region of N responsible for binding to human NR and for cell growth arrest maps to one of the three conserved boxes (Box1, aa 401–420) found in N of . This work unveils novel mechanisms by which distinct domains of MV-N may display different immunosuppressive activities, thus contributing to our comprehension of the immunosuppressive state associated with MV infection. Finally, MV-N domains may be good tools to target tumour cell proliferation and/or apoptosis.

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2005-06-01
2024-04-24
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Measles virus nucleoprotein induces cell-proliferation arrest and apoptosis through NTAIL–NR and NCORE–FcγRIIB1 interactions, respectively
J. Gen. Virol. 86, 1771 (2005); https://doi.org/10.1099/vir.0.80791-0
/content/journal/jgv/10.1099/vir.0.80791-0
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