Faculty Research
Leslie J. Parent
Assistant Professor
Medicine and Microbiology and Immunology
Graduate Program Affiliations:
Microbiology and Immunology, Cell and Molecular Biology, Molecular
Medicine/Integrative Biosciences, M.D./Ph.D.
M.D., Duke University School of Medicine, 1987; Postdoctoral training, Duke
University Medical Center, 1989-1991; Fellowship in Infectious Diseases, Penn
State University College of Medicine, 1991-1994; Postdoctoral training, Penn
State University College of Medicine, 1992-1997
E mail: lparent@psu.edu
Selected publications:
- Scheifele, L.Z., Garbitt, R.A., Rhodes, J.R., and Parent, L.J.
Nuclear entry and CRM1-dependent nuclear export of the Rous sarcoma virus
Gag polyprotein. Submitted.
- Garbitt, R.A., Kessler, M.D., Albert, J.A., and Parent, L.J. 2001. Trans-inhibition
of genomic RNA dimerization by Rous sarcoma virus matrix mutants. Journal
of Virology 75:260-268.
- Parent, L.J.,
Albert, J.A., Wilson, C.B., Wills, J.W and Craven, R.C.
2000. Dimerization defect in a Rous sarcoma virus matrix mutant. Journal of
Virology 74:164-172.
- Puffer, B., Parent, L.J., Wills, J.W. and Montelaro, R.C. 1997.
Equine infectious anemia virus utilizes a YXXL motif within the late
assembly domain of the Gag p9 protein. Journal of Virology
71:6541-6546.
- Craven, R.C. and Parent, L.J. 1996. Dynamic interactions of the Gag
polyprotein, in Current Topics in Microbiology and Immunology: Morphogenesis
and Maturation of Retroviruses, ed. H-G. Krausslich, 241:65-94.
- Parent, L.J.
, C.B. Wilson, M.D. Resh, J.W. Wills. 1996. Evidence for a
second function of the MA sequence in the Rous sarcoma virus Gag protein. Journal
of Virology 70:1016-1026.
- Parent, L.J.
, R.B. Bennett, R.C. Craven, J.B. Browzard, T.D. Nelle,
N.K. Krishna, C.B. Wilson, B. Puffer, R. Montelaro, and J.W. Wills. 1995.
Positionally independent and exchangeable late budding functions in the RSV
and HIV Gag proteins. Journal of Virology 69:5455-5460.
- Zhou, W., L.J. Parent, J.W. Wills, and M.D. Resh. 1994.
Identification of a membrane-binding domain within the amino-terminal region
of human immunodeficiency virus type 1 Gag protein which interacts with
acidic phospholipids. Journal of Virology 68:2556-69.
Overall goals:
Our research centers around understanding the interactions between viruses
and host cells at the molecular level. We use retroviruses as a model system to
dissect molecular mechanisms of virus replication, which has led us to study the
intracellular trafficking pathways of retroviral proteins and cellular factors
that are recruited to facilitate virus propagation.
Retrovirus replication:
The main structural proteins of the oncogenic retrovirus Rous sarcoma virus
(RSV) are the Gag proteins, which are initially synthesized as a polyprotein
precursor. The Gag polyprotein directs the assembly and budding of progeny
retrovirus particles from the plasma membrane of infected cells. Gag proteins
are synthesized on free ribosomes in the cytosol, and previously it was believed
that they were then targeted directly to the plasma membrane. However, recently
we discovered that the RSV Gag protein actually enters the nucleus using a
signal in the MA domain for nuclear targeting. Gag proteins are exported out of
the nucleus through the nuclear pore complex via the cellular exportin CRM-1
pathway and an interaction with the nuclear pore complex protein Nup214. After
nuclear export, Gag proteins form multimeric complexes using viral RNA as
scaffolding. The assembling virus particles are targeted to the plasma membrane
where they interact with cellular machinery to allow budding of nascent virions.
Gag proteins and the nuclear compartment:
One of our main goals is to understand what role Gag proteins play in the
nucleus. We are testing two main hypotheses. First, Gag or the MA protein might
be required early in infection, prior to the synthesis of the Gag polyprotein
precursor. Alternatively, the Gag polyprotein might enter the nucleus in order
to interact with the viral RNA to initiate the genome encapsidation process. We
are utilizing a multidisciplinary approach and a variety of techniques to test
these hypotheses. We are interested in the intracellular trafficking pathways
utilized by Gag proteins in their travel from cytosolic ribosomes to the
nucleus, back to the cytoplasm and then to the plasma membrane. By dissecting
the signals and factors involved in transport among subcellular compartments,
our research interfaces with basic questions in cellular biology.
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