In: Biology
How and where do many DNA viruses such as SV40 replicate in the host cell?
Simian virus 40 ( Sv40)
Viruses life cycles
SV40 replication in host cell
SV40 viruses are small (~40nm diameter), icosahedral, non-enveloped viruses that replicate in the nucleus.
Depending on the host cell, they can either transform the cell or replicate the virus and lyze the cell.
LYTIC
CYCLE
Attachment, penetration and uncoating
Viral capsid proteins interact with
cell surface receptors and penetration is probably via endocytosis.
Virions are transported to the nucleus and uncoated. DNA
(and associated histones)
enters nucleus, probably through a
nuclear pore
Production of viral mRNAs and
proteins
Gene expression is divided into early and late phases.
EARLY PHASE OF THE LYTIC CYCLE
Early gene expression
The early promoter is recognized by host RNA polymerase II (SV40 contains a strong enhancer). Post transcriptional RNA modification (capping, methylation, polyadenylation, splicing etc.) is carried out by host enzymes.
The early transcript (primary transcript) is made and then undergoes alternative processing, resulting in the mRNAs for the small T and large T antigens (these proteins have common amino-termini but different carboxy-termini).
The mRNAs are translated in the cytoplasm.
Note: Primary transcripts which can be processed and code for more than one protein are seen in several virus families and in the host cell.
LATE PHASE OF THE LYTIC CYCLE
The late phase starts with the onset of viral genome replication
DNA replication
Late gene expression
Large T-antigen
Origin of replication in Sv40
SV40 ori adjacent to trnscription control region.
Initiation of replication needs vial large T antigen (major product of early trancription) binding to:
T antigen helicase activity opens up replication bubble within ori core
Priming carried out by primase associated with the host DNA polymerase alpha.
SV40 Infection cycle
1. entry and release of core
2. Entry of DNA/ nucleosome complex to nucleus
3. Synthesis and alternative splicing of early(T) trancripts: proteinssynthesized
4. LT imported back to nucleus where it initiates DNA synthesis with host enzymes and potentiates late gene trnscription
5. Late gene mRNAs sythesized,spliced, exported, translated and products imported back to nucleus for particle assembly and release by unknown mechanism.