104 research outputs found
Freisetzung von Granulozyten-Elastase bei akutem Nierenversagen und während der Hämodialysebehandlung bei chronisch niereninsuffizienten Patienten
Freisetzung von Granulozyten-Elastase bei akutem Nierenversagen und während der Hämodialysebehandlung bei chronisch niereninsuffizienten Patienten
Hemodialysis, membrane-related neutrophil dysfunctions, and pentoxifylline — A pilot study
CMV Late Phase-Induced mTOR Activation Is Essential for Efficient Virus Replication in Polarized Human Macrophages : Antiviral Effects of mTOR Inhibitors
Human cytomegalovirus (CMV) remains one of the
most important pathogens following solid-organ
transplantation. Mounting evidence indicates that
mammalian target of rapamycin (mTOR) inhibitors
may decrease the incidence of CMV infection in solid-
organ recipients. Here we aimed at elucidating the
molecular mechanisms of this effect by employing
a human CMV (HCMV) infection model in human
macrophages, since myeloid cells are the principal
in
vivo
targets of HCMV. We demonstrate a highly di-
vergent host cell permissiveness for HCMV with opti-
mal infection susceptibility in M2 but not M1 polarized
macrophages. Employing an ultrahigh purified HCMV
stock we observed rapamycin-independent viral entry
and induction of IFN-b transcripts, but no proinflam-
matory cytokines or mitogen-activated protein kinases
and mTOR activation early after infection. However,
in the late infection phase, sustained mTOR activa-
tion was observed in HCMV-infected cells and was
required for efficient viral protein synthesis including
the viral late phase proteins pUL-44 and pp65. Accord-
ingly, rapamycin strongly suppressed CMV replication
3 and 5 days postinfection in macrophages. In conclu-
sion, these data indicate that mTOR is essential for
virus replication during late phases of the viral cycle in
myeloid cells and might explain the potent anti-CMV
effects of mTOR inhibitors after organ transplantatio
- …