BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Role of Ca2+ in rotavirus entry\, assembly and the pathogenesis of
  diarrhoea - Professor Fabian Michelangeli\, Department of Physiology\, De
 velopment and Neuroscience\, Cambridge
DTSTART:20110309T163000Z
DTEND:20110309T173000Z
UID:TALK28481@talks.cam.ac.uk
CONTACT:Suzy Blows
DESCRIPTION:Ca2+ plays a key role in many pathological processes\, includi
 ng viral infections. Rotavirus\, the major etiological agent of viral gast
 roenteritis in children and young animals\, provides a useful model to stu
 dy a number of Ca2+ dependent virus-cell interactions. Rotavirus entry\, a
 ctivation of transcription\, morphogenesis\, cell lysis and particle relea
 se are Ca2+-dependent processes. In the extracellular medium\, Ca2+ stabil
 izes the structure of the viral capsid formed by three concentric protein 
 layers. The mechanism by which rotavirus and other nonenveloped viruses en
 ter the cell is still not clear. We have proposed an endocytosis model whe
 re the critical step for virus uncoating and membrane permeabilization is 
 the decrease in Ca2+concentration in the endosome. Low Ca2+ in the endosom
 e would induce solubilization of coat proteins and permeabilization of the
  vesicle to release double layer particles (DLP) in the cytoplasm and acti
 vate transcriptase. Newly form DLP bud into the ER for the acquisition of 
 the capsid outer layer and requires a high Ca2+ concentration inside this 
 compartment. Infection modifies Ca2+ homeostasis of the cell\, increasing 
 plasma membrane Ca2+ permeability leading to elevation of [Ca2+]i\, and ER
  Ca2+ content\, which may be advantageous to virus replication. These chan
 ges have been associated to the expression of the glycosylated nonstructur
 al viral protein NSP4. The mechanisms involved in Ca2+ entry are unknown\,
  but NSP4 may act as a viroporin and/or activate the Na+/Ca2+ exchanger (N
 CX) operating in the reverse mode. An elevated Ca2+ concentration induces 
 cell dysfunction and\, eventually\, cell death. The role of these changes 
 in the production of diarrhoea will be discussed.
LOCATION:Lecture Theatre 1\, Department of Veterinary Medicine
END:VEVENT
END:VCALENDAR