SIMIAN VIRUS 40 REPLICATION

Mukund S. Vats
Introduction
… Simian virus 40 (SV40), a polyomavirus, discovered in 1960 as a
contaminant of polio vaccines.
… SV40 is a potent DNA tumor virus that induces tumors in rodents and
transforms many types of cells in culture, including those of human
origin.
… The viral replication protein, named large T antigen (T-ag), is also the
viral oncoprotein.
… There is a single serotype of SV40, but multiple strains of virus exist
that are distinguishable by nucleotide differences in the regulatory
region of the viral genome and in the part of the T-ag gene.
Classification & Identification
… SV40 is classified as a member of the Polyomavirus
genus of the family Papovaviridae,
„ Morphology → Icosahedral capsid
„ Genetic Material → dsDNA genome (Circular)
… Although there is only one known serotype of SV40,
different viral strains do exist and can be
distinguished by variations in the structure of the
viral regulatory region and in the nucleotide
sequence of the extreme C terminus of the T-ag
gene.
Genome
… SV40 codes, at least, for six viral
proteins:
† 2 early genes, for large tumor
antigen (LT-Ag) and small tumor
antigen ( ST-Ag),
† 1 agnoprotein (AGNO), probably
involved in the assembly of viral
particles and processing of late
mRNA
† 3 capsid proteins, VP1, VP2, VP3
† 1 Very late gene VP4 for lytic
release.
… The early and late genes are
transcribed on different DNA strands
in a way that the transcription
proceeds divergently from the
regulatory region
Oncogenicity
… The T- antigen both large and small are
responsible for the oncogenicity.

P6 / P7 /T-Ag
Replication
… The cell infection starts by the binding of the SV40 virus
receptor to the major histocompatibility complex
… After binding to the cell surface, virus capsid undergoes
endocytosis and is transported to the nucleus .
… SV40 enters cells by caveola-mediated endocytosis .
… The primary transcript from the early region is alternatively
spliced to give two mRNAs that encode large Tag and small
tag.
… Tag is a nuclear phosphoprotein of 94 kD and it is an essential
factor for DNA replication & early regulation.
… It binds to the viral origin of replication (ori) & promotes
initiation
Replication (Cont....)

… SV40 relies on cellular enzymes and cofactors for DNA.

… Tag modulates cellular signaling pathways by its ablity to bind
several cellular molecules
… It induce cells to enter S phase and this accounts for the ability
of Tag to transform cells.
… It also affects pathways that control cell cycle progression and
… apoptosis.
… The role of the small tag in the polyomavirus life cycle is less
clear.
Replication (Concise)

… Virus attaches to host receptors and is endocytosed into vesicles in the host
cell.
… Virion transits through endoplasmic reticulum where host protein disulfide
isomerases rearrange its capsid structure
… Export of misfolded virion to the cytoplasm possibly through
host ERAD pathway
… Loss of VP1 in the low-calcium conditions of the cytosol
… Import of genomic DNA into host nucleus.
… Transcription of early genes (LT and sT genes)
… Replication of the DNA genome in the nucleus.
… Transcription of late genes encoding for structural proteins
(VP1, VP2 and VP3).
… Assembly of new virions in the nucleus.
… Virions are released by lysis of the cell.
References
… Simian virus 40 in humans (http://www.infectagentscancer.com/content/2/1/13)
… Cell and Molecular Biology of Simian Virus 40: Implications for Human
Infections and Disease, Journal of the National Cancer Institute, Vol. 91, No. 2,
January 20, 1999