Measles virus induces expression of SIP110, a constitutively membrane clustered lipid phosphatase, which inhibits T cell proliferation

Open Access
Publisher Website
Google Scholar
Abstract
Interference of measles virus (MV) with phosphatidyl‐inositol‐3‐kinase (PI3K) activation in response to T cell receptor ligation was identified as important for the induction of T cell paralysis. We now show that MV exposure of unstimulated T cells induces expression of SIP110, an isoform of the lipid phosphatase SHIP145, which is translated from an intron‐derived sequences containing mRNA. We found that MV contact can regulate stimulated exon inclusion into pre‐mRNAs by targeting PI3K or MAPK‐dependent nuclear translocation and activation of splicing regulatory serine–arginine rich (SR) and Sam68 proteins. Induction of SIP110 in resting T cells relied on MV‐dependent interference with basal activity of the PI3K. SIP110 was cloned from MV‐exposed T cells, and, when transiently expressed in primary or Jurkat T cells, localized into membrane clusters independently of T cell activation. Confirming that SIP110 is a catalytically active lipid phosphatase, its transgenic expression abolished basal and impaired PMA/ionomycin‐stimulated phosphorylation of the Akt kinase which is important for T cell proliferation. Thus MV causes induction of SIP110 expression, which constitutively depletes the cellular phosphoinositol‐3,4,5‐phosphate pool suggesting that thereby the threshold for activation signals necessary for the induction of T cell proliferation is raised.