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. 2013;9(7):e1003321.
doi: 10.1371/journal.ppat.1003321. Epub 2013 Jul 4.

Papillomaviruses use recombination-dependent replication to vegetatively amplify their genomes in differentiated cells

Nozomi Sakakibara  1 , Dan Chen, Alison A McBride
Affiliations

Papillomaviruses use recombination-dependent replication to vegetatively amplify their genomes in differentiated cells

Nozomi Sakakibara et al. PLoS Pathog. 2013.
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The papillomavirus life cycle is closely coupled with differentiation of the host epithelium.
The virus infects the dividing basal cells through a microabrasion. The viral DNA is maintained at a low copy number in these cells. When basal cells divide, some daughter cells move up in the epithelium and begin the process of terminal differentiation. Papillomaviruses are finely tuned to this process and turn on late transcription, translation, and late DNA replication in specific stages of the differentiation process. Vegetative viral DNA replication takes place in cells that are in either the G2 phase of the cell cycle or have exited the cell cycle. By inducing the DNA damage response and homologous recombination repair pathways, the virus can efficiently replicate progeny genomes in differentiated cells without competition from host DNA synthesis.
Figure 2
Figure 2. CIN612-9E cells were derived from a cervical lesion and contain hundreds of copies of extrachromosomally replicating HPV31 genomes .
These cells can be induced to differentiate with high calcium–containing medium, which switches on vegetative viral DNA replication . Many of these cells contain multiple small replication foci , ; but numerous cells contain one large foci, as shown here, perhaps indicative of a temporal evolution. The nucleus shown has been stained with DAPI (grey) and antibodies to γH2AX to identify the viral replication foci (shown in cyan), and RAD51 to identify centers of homologous recombination (shown in red). 3D reconstruction of Z-stacks of confocal images was performed using Bitplane Imaris.
See this image and copyright information in PMC

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