SV40
receptor?
stimulate endocytosis or fusion?
Uncoating:
Genome replication:
Protein synthesis:
Polyomavirus genus
SV40
mouse Py
human BKV
human JCV
Maturation:
structure
genome packaging
Isolated in 1960
Release:
lysis how?
SV40 structure
SV40 structure
Icosahedron:
Icosahedron
T=1
T=3
SV40 replication
Attachment
Receptor appears to be MHC I
VP1 (only exposed protein) binds
receptor
Entry
Receptor-mediated endocytosis
VP2, VP3 may interact with
membrane
Probably enters ER
Transported into nucleus;
mechanism uncertain
Uncoating occurs in nucleus;
requires VP2, VP3
T=7
3 capsid proteins: VP1, VP2, VP3
60 subunits with 5 VP1 proteins each
T=4
SV40 replication
Early gene expression
Genome is minichromosome with
histones (5243 bp)
Host factors recognize
TATA box and enhancer
of early promoter (PE)
SV40 replication
Early gene expression
small-t and large-T antigen mRNA made by alternative splicing
Translation by host factors
SV40 replication
Late gene expression
T Ag binds promoter region
Activates PL while blocking PE
SV40 replication
Genome replication
T Ag binds host Rb and p53
Removes contact inhibition DNA replication initiated
Blocks induction of apoptosis
T Ag binds SV40 origin acts as initiator protein
Host helicase, primase, polymerase, etc. replicate DNA
Circular DNA: no ends, so no end problem
SV40 replication
Assembly & Release
Virus proteins have
nuclear localization
signals
Assembly occurs in
nucleus
Some virus transported
to surface in vesicles
Cell eventually lyses
(virus production
relatively slow)
SV40 transformation
Abortive infection in nonpermissive cells (e.g., mouse)
Entry and T Ag synthesis occur normally
No DNA synthesis
DNAP cant interact with T Ag at origin?
T Ag binds Rb and p53
Cells lose contact inhibition and replicate: transformed
Rarely, SV40 DNA integrates into nuclear DNA
Stable transformation if this occurs