1887

Abstract

The E1 and E2 proteins encoded by papillomaviruses are required for viral DNA replication. Although E1 is the replication initiator protein, previous studies have shown that the full-length E1 protein binds to the origin weakly and with low sequence specificity. The E2 protein facilitates binding of the E1 protein to the origin, triggering the initiation of replication. The E1 protein contains ATPase, helicase and DNA unwinding activities. studies with mucosal human papillomavirus (HPV) types 11 and 18 have shown that while E1 is absolutely essential for replication, the E1 binding site is dispensable. However, both the E2 protein and E2 binding sites are required for their replication. In contrast to these HPVs, transient replication of HPV type 1, which infects cutaneous tissue, requires only the viral E1 protein and E1 binding site. To understand the basis for these differences, we have overexpressed and purified the HPV-1 E1 and E2 proteins and studied their biochemical properties. The purified E1 protein was shown to have an ATPase activity with a very low value, similar to that of the SV40 large T antigen. The E1 protein bound to the HPV-1 origin in the absence of the E2 protein and without the use of any cross-linking agents. Our results suggest that the ability of the HPV-1 E1 protein to initiate DNA replication in the absence of the E2 protein may be due to its stable interaction with the HPV-1 origin.

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2003-02-01
2020-05-28
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