At the End of One's Tether

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Science  14 May 2004:
Vol. 304, Issue 5673, pp. 929
DOI: 10.1126/science.304.5673.929a

Some DNA viruses, like papillomavirus, permanently reside within a host by establishing a latent infection within host cells. In order to maintain the viral genome inside the nuclei of dividing host cells, the virus must devise a strategem for ensuring faithful partitioning to daughter cell nuclei during disassembly and reassembly of the nuclear envelope. You et al. examined how bovine papillomavirus manages to accomplish this feat and find that one of the papillomavirus-encoded proteins, E2, tethers the viral genome to host chromosomes during mitosis. On the host chromosome, a protein termed Brd4 acts as the anchor for E2; Brd4 and E2 colocalize on mitotic chromosomes. Expression of the C-terminal domain of Brd4, which contains the E2 binding site but which cannot interact with chromosomes, inhibits association of the viral genome with host chromosomes. In mouse cells, blocking the Brd4-E2 interaction inhibits papillomavirus DNA-induced transformation. This interaction appears key to the maintenance of papillomavirus in latently infected cells and is thus a potential therapeutic target. — SMH

Cell 117, 349 (2004).

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