Requirements for species-specific papovavirus DNA replication
Abstract
<jats:p>Replication of papovavirus DNA requires a functional replication origin, a
virus-encoded protein, large T antigen, and species-specific permissive factors. How
these components interact to initiate and sustain viral DNA replication is not known.
Toward that end, we have attempted to identify the viral target(s) of permissive factors.
The functionally defined replication origins of polyomavirus and simian virus 40,
two papovaviruses that replicate in different species (mice and monkeys, respectively),
are composed of two functionally distinct domains: a core domain and an auxiliary
domain. The origin cores of the two viruses are remarkably similar in primary structure
and have common binding sites for large T antigen. By contrast, their auxiliary domains
share few sequences and serve as binding sites for cellular proteins. It seemed plausible,
therefore, that if cellular permissive factors interacted with the replication origin,
their targets were likely to be in the auxiliary domain. To test this hypothesis we
constructed hybrid origins for DNA replication that were composed of the auxiliary
domain of one virus and the origin core of the other and assessed their capacity to
replicate in a number of mouse and monkey cell lines, which express the large T antigen
of one or the other virus. The results of this analysis showed that the auxiliary
domains of the viral replication origins could substitute for one another in DNA replication,
provided that the viral origin core and its cognate large T antigen were present in
a permissive cellular milieu. Surprisingly, the large T antigens of the viruses could
not substitute for one another, regardless of the species of origin of the host cell,
even though the two large T antigens bind to the same sequence motif in vitro. These
results suggest that species-specific permissive factors do not interact with the
origin-auxiliary domains but, rather, with either the origin core or the large T antigen
or with both components to effect DNA replication.</jats:p>
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https://hdl.handle.net/10161/23900Published Version (Please cite this version)
10.1128/jvi.63.12.5371-5385.1989Publication Info
Bennett, ER; Naujokas, M; & Hassell, JA (1989). Requirements for species-specific papovavirus DNA replication. Journal of Virology, 63(12). pp. 5371-5385. 10.1128/jvi.63.12.5371-5385.1989. Retrieved from https://hdl.handle.net/10161/23900.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Ellen Ruth Bennett
Adjunct Assistant Professor in the Department of Neurology

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