Molecular Analysis of the Retroviral Budding Mechanism

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): The diseases caused by retroviruses (e.g.,
AIDS and cancer) cannot be cured and have no vaccines for prevention.
Therefore, a better understanding of the viruses that cause these diseases is
needed. One of the least understood parts of the retrovirus replication cycle
is budding, the step during which new virus particles emerge from the
infected-cell surface and are release to spread the infection to new cells.
Budding is mediated by the Gag protein, and during previous funding periods we
have identified and characterized the primary domains (the M, I, and L domains)
of this protein that are needed for particle released from the plasma membrane.
Although a good understanding of Gag proteins has been acquired, the
contributions of the host cell to the budding process are a mystery. The
long-range goal of this Continuation Application is to identify and
characterize the host factors required for budding. This is a challenging
endeavor, but fortunately, glimpses of the host machinery have been made during
the previous funding period. Interestingly, all the evidence points towards the
involvement of components of the endocytic and vesicular trafficking machinery
of the cell. We request funding to pursue two large Specific Aims. The first is
to thoroughly analyze the role of ubiquitin in retrovirus budding. During the
previous funding period, we discovered that this host protein is actually part
of the budding machinery at the plasma membrane. This raises a variety of
important clues and questions that need to be addressed. The second aim is to
identify and characterize additional host proteins that are involved in
budding. Again, clues from our previous work provide guidance on how to do
this. For both aims, the primary focus will be Rous sarcoma virus, but as in
the previous funding periods, we will utilize other enveloped viruses when they
offer the possibility of gaining additional insights. Indeed, we have shown
that the mechanism of budding used by retroviruses has features in common with
unrelated viruses, and hence what we learn from these studies is likely to be
useful for a variety of other viral diseases as well.
StatusFinished
Effective start/end date6/20/015/31/07

Funding

  • National Cancer Institute: $487,030.00
  • National Cancer Institute: $472,846.00
  • National Cancer Institute: $501,640.00
  • National Cancer Institute: $445,700.00
  • National Cancer Institute: $459,072.00

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