Integration (Retrovirus)After the appearance of the full-length dsDNA genome in the nucleus, the viral integrase catalyzes it insertion into a host cell chromosome by means of a single recombinational event. Insertion is essentially random within the host genome. The first event in integration is the removal of two nucleotides from the 3’ end of both strands of the viral DNA. The next two nucleotides are always AC, from 3’ to 5’. The 3’ OH of the now 3’-terminal A residue is used to attack an internucleotide phosphate in the host DNA. Attack is coordinated so that both ends of the viral DNA are inserted at once. The spacing between the two insertion points depends on the viral integrase and is 4, 5, or 6 nucleotides in different viruses. The ends of the inserted structure are then cleaned up, probably by host enzymes. Insertion results in the loss of the two terminal nucleotides of the viral DNA. In addition, a duplication of the 4, 5, or 6 nucleotides of the host that lie between the two insertion points is produced, and these duplicated nucleotides flank the two ends of the viral genome.
The integrated form of the virus, the provirus, is stable. No mechanism for precise excision of the provirus is known, and integration is essentially irreversible. Most
Retroviruses do not kill the host cell, and the provirus behaves as a simple Mendelian gene that is transmitted to all daughter cells. It is obvious that insertion of such a provirus into the germ line would lead to its transfer to progeny organisms, which appears to have occurred many times in the past.
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