Simian Virus 40 Replication

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SIMIAN VIRUS 40 REPLICATION

Mukund S. Vats



Introduction

Simian virus 40 (SV40), a polyomavirus, discovered in 1960 as acontaminant of polio vaccines.

SV40 is a potent DNA tumor virus that induces tumors in rodents andtransforms many types of cells in culture, including those of humanorigin.

The viral replication protein, named large T antigen (T-ag), is also theviral oncoprotein.

There is a single serotype of SV40, but multiple strains of virus existthat are distinguishable by nucleotide differences in the regulatoryregion 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 bedistinguished by variations in the structure of the

viral regulatory region and in the nucleotidesequence of the extreme C terminus of the T-aggene.



Genome

SV40 codes, at least, for six viralproteins:

2 early genes, for large tumor

antigen (LT-Ag) and small tumorantigen ( ST-Ag),

1 agnoprotein (AGNO), probablyinvolved in the assembly of viralparticles and processing of latemRNA

3 capsid proteins, VP1, VP2, VP3

1 Very late gene VP4 for lyticrelease.

The early and late genes are

transcribed on different DNA strandsin a way that the transcriptionproceeds divergently from theregulatory region



Oncogenicity

P6 / P7 /T-Ag

The T- antigen both large and small are

responsible for the oncogenicity.



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) & promotesinitiation



Replication (Cont....)

SV40 relies on cellular enzymes and cofactors for DNA.

Tag modulates cellular signaling pathways by its ablity to bindseveral 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 lessclear.



Replication (Concise)

Virus attaches to host receptors and is endocytosed into vesicles in the host

cell.

Virion transits through endoplasmic reticulum where host protein disulfideisomerases 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

http://www.infectagentscancer.com/content/2/1/13

http://www.infectagentscancer.com/content/2/1/13

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Simian Virus 40 Replication