AIDS and Cancer Virus Program
Robert J. Gorelick received his Ph.D. in 1985 from the University of Delaware, Department
of Chemistry and Biochemistry studying enzymology of flavoproteins involved in fatty
acid metabolism and electron transport. In 1985, he began his postdoctoral research
with the ABL-Basic Research Program, Frederick National Laboratory for Cancer Research,
and received an NIH National Research Service Award from 1988 to 1990 focusing efforts
on determining the function of retroviral nucleocapsid proteins in virus assembly
and infection processes. In 1990, Dr. Gorelick joined the AIDS and Cancer Virus
Program serving as the Head of the Retroviral Mutagenesis Section since 1995.
The majority of the research from this section focuses on retroviral nucleocapsid
(NC) proteins and their highly conserved CCHC (-Cys-X2-Cys-X4-His-X4-Cys-)
Zn2+-fingers, located in Gag. Site-directed mutagenesis, protein chemistry,
and cell culture techniques are used to study the functions of NC proteins in viral
replication. Remarkable defects in viral assembly and replication processes result
from various conservative alterations to NC and its highly conserved Zn2+-finger
structures. Deficiencies included a reduction in the level of packaged genomes and
severe defects in replication. Some mutants can package significant levels of genomic
RNA, yet remain as much as 106-fold less infectious than wild-type virus;
compelling evidence demonstrating NC's involvement in assembly processes as well
as other functions in viral infection. Extended studies have determined precisely
what steps are disrupted in the replication process upon altering NC. Cell culture-based
results show the involvement of NC in i) reverse transcription processes, ii) integration
processes, and iii) the correct timing of reverse transcription initiation. The
knowledge gained from these studies shows that NC and its Zn2+-fingers
are extremely sensitive to mutagenic or chemical alteration, thus they are attractive
This Section is also involved in the preparation, purification and distribution
of mutant and wild-type recombinant NC proteins and full-length viral genomes to
qualified research laboratories upon request by contacting Dr. Robert Gorelick (email@example.com). NC proteins
are produced and purified with the expert assistance of the ACVP Retroviral Protein
Chemistry Core and genomes are prepared from virus generated by the ACVP Biological
Products Core. The purpose of this endeavor is to assist other laboratories in assessing
the molecular determinants of NC function. Such studies have greatly extended the
understanding of the properties and functions of NC in viral replication.
- Judith G. Levin, NICHD, NIH
- Gilles Mirambeau, University of Barcelona, Spain
- Karin Musier-Forsyth, The Ohio State University
- Alan Rein, NCI
- Kevin M. Weeks, University of North Carolina-Chapel Hill
- Mark C. Williams, Northeastern University
- Gherghe, C., T. Lombo, C. W. Leonard, S. A. K. Datta, J. W. Bess, R. J. Gorelick,
A. Rein, and K. M. Weeks. 2010. Definition of a high-affinity Gag recognition structure
mediating packaging of a retroviral RNA genome. Proc. Natl. Acad. Sci. U.S.A. 107:19248-53.
- Mirambeau, G., S. Lyonnais, D. Coulaud, L. Hameau, S. Lafosse, J. Jeusset, I. Borde,
M. Reboud-Ravaux, T. Restle, R. J. Gorelick, and E. Le Cam. 2007. HIV-1 protease
and reverse transcriptase control the architecture of their nucleocapsid partner.
PLoS One. 2:e669.
- Mirambeau, G., S. Lyonnais, and R. J. Gorelick. 2010. Features, processing states,
and heterologous protein interactions in the modulation of the retroviral nucleocapsid
protein function. RNA Biol. 7:85-95.
- Qualley, D. F., K. M. Stewart-Maynard, F. Wang, M. Mitra, R. J. Gorelick, I. Rouzina,
M. C. Williams, and K. Musier-Forsyth. 2010. C-terminal domain modulates the nucleic
acid chaperone activity of human t-cell leukemia virus type 1 nucleocapsid protein
via an electrostatic mechanism. J. Biol. Chem. 285:295-307.
- Thomas, J. A., W. J. Bosche, T. L. Shatzer, D. G. Johnson, and R. J. Gorelick. 2008.
Mutations in human immunodeficiency virus type 1 nucleocapsid protein zinc fingers
cause premature reverse transcription. J. Virol. 82:9318-9328.
- Thomas, J. A., T. D. Gagliardi, W. G. Alvord, M. Lubomirski, W. J. Bosche, and R.
J. Gorelick. 2006. Human immunodeficiency virus type 1 nucleocapsid zinc-finger
mutations cause defects in reverse transcription and integration. Virology 353:41-51.
- Thomas, J. A., and R. J. Gorelick. 2008. Nucleocapsid protein function in early
infection processes. Virus Res. 134:39-63.
- Thomas, J. A., D. E. Ott, and R. J. Gorelick. 2007. Efficiency of human immunodeficiency
virus type 1 postentry infection processes: Evidence against disproportionate numbers
of defective virions. J. Virol. 81:4367-4370.
- Watts, J. M., K. K. Dang, R. J. Gorelick, C. W. Leonard, J. W. Bess Jr, R. Swanstrom,
C. L. Burch, and K. M. Weeks. 2009. Architecture and secondary structure of an entire
HIV-1 RNA genome. Nature 460:711-716.
- Wilkinson, K. A., R. J. Gorelick, S. M. Vasa, N. Guex, A. Rein, D. H. Mathews, M.
C. Giddings, and K. M. Weeks. 2008. High-throughput SHAPE analysis reveals structures
in HIV-1 genomic RNA strongly conserved across distinct biological states. PLoS
- James A. Thomas, Ph.D., Scientist I
- Donald G. Johnson, Research Associate II
- William J. Bosche, Research Associate II