Natural biology of polyomavirus middle T antigen.

"It has been commented by someone that 'polyoma' is an adjective composed of a prefix and suffix, with no root between--a meatless linguistic sandwich" (C. J. Dawe). The very name "polyomavirus" is a vague mantel: a name given before our understanding of these viral agents was clear but implying a clear tumor life-style, as noted by the late C. J. Dawe. However, polyomavirus are not by nature tumor-inducing agents. Since it is the purpose of this review to consider the natural function of middle T antigen (MT), encoded by one of the seemingly crucial transforming genes of polyomavirus, we will reconsider and redefine the virus and its MT gene in the context of its natural biology and function. This review was motivated by our recent in vivo analysis of MT function. Using intranasal inoculation of adult SCID mice, we have shown that polyomavirus can replicate with an MT lacking all functions associated with transformation to similar levels to wild-type virus. These observations, along with an almost indistinguishable replication of all MT mutants with respect to wild-type viruses in adult competent mice, illustrate that MT can have a play subtle role in acute replication and persistence. The most notable effect of MT mutants was in infections of newborns, indicating that polyomavirus may be highly adapted to replication in newborn lungs. It is from this context that our current understanding of this well-studied virus and gene is presented.

Approaches to study interactions between small DNA viruses and differentiated tissue.

Polyomavirus (Py) derives its name from the early observation of multiple tumors that develop in newborn mice following inoculation with this family of viruses. In nature, however, tumor development is rare in the virus life cycle, rather a two-phase infection occurs, acute and persistent, resulting in a final latent infection in the kidneys. The acute phase induces an antiviral immune response, although no recognizable inflammation, which can last the lifetime of the mouse, even passing on antibodies to its offspring. The structure, replication, and expression of the Py viral genome in permissive and nonpermissive infections has been studied extensively in various cell culture systems. However, the nature of Py expression, replication, and immunopathogenesis in mice has not been thoroughly researched.