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SUMMARY:Evolution of viral host ranges through alterations of receptor bin
 ding - canine and feline parvovirus capsid interactions with host transfer
 rin receptors and antibodies. - Colin R. Parrish\, Professor of Virology\,
  Baker Institute for Animal Health\, College of Veterinary Medicine\, Corn
 ell University\, Ithaca\, NY
DTSTART:20081014T113000Z
DTEND:20081014T123000Z
UID:TALK13988@talks.cam.ac.uk
CONTACT:Suzy Blows
DESCRIPTION:Canine parvovirus (CPV) emerged in 1978 and spread worldwide\,
  and is now a widespread endemic virus of dogs.  CPV is a host range varia
 nt of the feline panleukopenia virus (FPV).  Between 1979 and 1980 the ori
 ginal CPV strain (CPV-2) was replaced worldwide by an antigenic and host r
 ange variant (CPV-2a).  The new canine host range of CPV was determined by
  changes within three capsid positions\, and those changes also alter the 
 antigenic structure of the capsid.  The capsids bind the transferrin recep
 tor (TfR) on feline cells\, but canine cell infection requires the additio
 nal ability to bind the canine TfR.  The feline and canine TfRs were expre
 ssed and purified\, and distinct binding properties were seen for each rec
 eptor-capsid combination.  Purified complexes of capsids with the feline T
 fR complexes showed only 1 to 3 TfRs bound per capsid\, fewer than the 20 
 to 24 predicted.  \n\nAntibodies have been suggested to bind primarily to 
 two positions on the capsid\; site A on a raised region near the threefold
  axis of symmetry\, and site B on a ridge on the side of that raised regio
 n.  However\, when the true binding sites of 8 different antibodies were i
 dentified by cryo-EM reconstructions of antibody Fabs with capsids those s
 howed that the antibodies contacted >60% of the capsid surface.  There is 
 complete overlap of the receptor and many antibody binding sites\, but som
 e of those antibodies did not neutralize efficiently as Fabs.  Two Fabs th
 at did neutralize to high levels bound to antigenic site B in a particular
  orientation.  Surprisingly\, the two common regions of overlap between th
 e groups of antibodies coincided almost exactly with the positions of know
 n escape mutations of the viruses.  As many changes in the capsids affect 
 both antibody and TfR binding\, this suggests complex selection pressures 
 on the virus structure.\n\n
LOCATION:Lecture Theatre 2\, Department of Veterinary Medicine
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