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Journal of Virology, April 2000, p. 3046-3057, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Basic Residues in Human Immunodeficiency Virus Type 1 Nucleocapsid Promote Virion Assembly via Interaction with
RNA
Andrea
Cimarelli,1
Sara
Sandin,2
Stefan
Höglund,2 and
Jeremy
Luban1,3,*
Departments of
Microbiology1 and
Medicine,3 College of Physicians and
Surgeons, Columbia University, New York, New York 10032, and
Department of Biochemistry, Biomedical Center, Uppsala,
Sweden2
Received 16 September 1999/Accepted 5 December 1999
Retroviral Gag polyproteins drive virion assembly by polymerizing
to form a spherical shell that lines the inner membrane of nascent
virions. Deletion of the nucleocapsid (NC) domain of the Gag
polyprotein disrupts assembly, presumably because NC is required for
polymerization. Human immunodeficiency virus type 1 NC possesses two
zinc finger motifs that are required for specific recognition and
packaging of viral genomic RNA. Though essential, zinc fingers and
genomic RNA are not required for virion assembly. NC promiscuously
associates with cellular RNAs, many of which are incorporated into
virions. It has been hypothesized that Gag polymerization and virion
assembly are promoted by nonspecific interaction of NC with RNA.
Consistent with this model, we found an inverse relationship between
the number of NC basic residues replaced with alanine and NC's
nonspecific RNA-binding activity, Gag's ability to polymerize in vitro
and in vivo, and Gag's capacity to assemble virions. In contrast,
mutation of NC's zinc fingers had only minor effects on these properties.
*
Corresponding author. Mailing address: Departments of
Microbiology and Medicine, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-8706. Fax: (212) 305-0333. E-mail:
Luban{at}cuccfa.ccc.columbia.edu.
Journal of Virology, April 2000, p. 3046-3057, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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[Full Text]
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