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Natural biology of polyomavirus middle T antigen
1Department of Molecular Biology and Biochemistry, Biological Sciences II, University of California-Irvine, Irvine, CA 92697, USA.
Abstract:
"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.
Insights
Polyomavirus middle T antigen (MT) is not essential for viral replication in adult mice. MT mutants show impaired replication only in newborn mice, suggesting polyomavirus is adapted to neonatal lung infections.
Area of Science:
- Virology
- Molecular Biology
- Oncology
Background:
- The name "polyomavirus" implies tumor-inducing capabilities, but this is not inherent to the virus.
- The middle T antigen (MT) is a key transforming gene product of polyomavirus.
- Previous understanding of polyomavirus biology and MT function was limited.
Purpose of the Study:
- To redefine polyomavirus and its middle T antigen (MT) gene based on natural biology and function.
- To investigate the in vivo role of MT in polyomavirus replication and persistence.
- To clarify the natural function of MT beyond its association with transformation.
Main Methods:
- In vivo analysis of polyomavirus middle T antigen (MT) function.
- Intranasal inoculation of adult SCID mice with wild-type and MT-mutant polyomaviruses.
- Comparison of viral replication levels in adult and newborn mice.
Main Results:
- Polyomavirus replicates to high levels in adult SCID mice even with MT lacking transformation functions.
- MT mutants replicate similarly to wild-type viruses in adult competent mice, indicating a subtle role in acute replication and persistence.
- MT mutants exhibit significantly reduced replication in newborn mice, suggesting adaptation to neonatal hosts.
Conclusions:
- Middle T antigen (MT) is not essential for polyomavirus replication in adult immunocompetent or SCID mice.
- Polyomavirus appears highly adapted for replication in newborn lungs.
- The function of MT in polyomavirus pathogenesis requires re-evaluation in the context of natural infection dynamics.
