# MECHANISMS IN PAPOVAVIRUS ASSEMBLY

> **NIH NIH R01** · DANA-FARBER CANCER INST · 1992 · $255,058

## Abstract

The structures of several plant and animal viruses are now known to near
atomic resolution, and represent some of the most complex biological
assemblies understood.  These structures provide a rational basis for
studying virus-cell interactions, as well as designing anti-viral
therapeutic agents.  Although the final virion structures are defined, the
mechanisms involved in assembling these structures are still largely
unknown.  This knowledge is significant not only to the problems of protein
folding, regulation of other protein assemblies, and the interaction of
structural proteins with eukaryotic chromosomes, but also provides another
target (i.e. the assembly process rather than the final structure) for
possible therapeutic intervention.  In addition to other DNA viruses, the
papovaviruses themselves are a relevant target for anti-viral agents.
Papillomaviruses are already of recognized medical importance, and in an
era of immunosuppression secondary to transplantation regimens, cancer
chemotherapy, and HIV infection, human polyomaviruses also may be more
frequently encountered as pathogenic agents.

The purpose of this proposal is to use papovaviruses as a model system to
understand how DNA virus assembly is regulated, and to define the relative
importance of different protein bonding interactions in forming the final
virus structure.  Three experimental approaches utilize purified
recombinant polyomavirus capsid proteins to study protein-protein and
protein-chromatin interactions in vitro.  Site-directed mutagenesis of
recombinant polyoma VP1 oat proteins expressed in bacteria will be used to
assess the relative contribution of specific intercapsomeric bonds to
capsid stability and assembly in vitro.  Recombinant VP1 proteins will also
be used to identify assembly intermediates in forming capsids in vitro, and
determine whether bonding interactions between coat proteins are
functionally conserved between the murine polyoma and SV40 viruses.
Recombinant VP2 and VP3 coat proteins will be used to study their possible
interaction with VP1 and the viral minichromosome.  Capsid proteins
expressed in insect cells using baculovirus vectors will e used to study
the regulation of capsid assembly in vivo.  Combinatorial infections with
vectors expressing these proteins will determine the contribution of the
VP2 and VP3 proteins to the nuclear transport of VP1 and to the
ultrastructure of the viral capsid.  Finally, approaches used to study
polyomavirus assembly will be extended to investigate bovine papillomavirus
(BPV) coat proteins, and BPV virus purified from bovine warts will be used
to crystallize this prototype papillomavirus for high resolution structural
analysis.  The ultimate goal of these studies will be to compare the
strategies of assembly between polyoma and papillomaviruses, and identify
general principles in constructing a T=7 icosahedral DNA virus.

## Key facts

- **NIH application ID:** 3175459
- **Project number:** 2R01CA037667-09
- **Recipient organization:** DANA-FARBER CANCER INST
- **SAM.gov UEI:** DPMGH9MG1X67
- **Principal Investigator:** Robert L Garcea
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $255,058
- **Award type:** 2
- **Project period:** 1984-07-01 → 1993-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175459

## Citation

> US National Institutes of Health, RePORTER application 3175459, MECHANISMS IN PAPOVAVIRUS ASSEMBLY (2R01CA037667-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175459. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*