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Journal of Virology, January 2001, p. 242-250, Vol. 75, No. 1
Department of Microbiology and Immunology,
The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033
Received 13 June 2000/Accepted 27 September 2000
The major structural protein of the retroviral core (CA) contains a
conserved sequence motif shared with the CA-like proteins of distantly
related transposable elements. The function of this major region of
homology (MHR) has not been defined, in part due to the baffling array
of phenotypes in mutants of several viruses and the yeast TY3. This
report describes new mutations in the CA protein of Rous sarcoma virus
(RSV) that were designed to test whether these different phenotypes
might indicate distinct functional subdomains in the MHR. A comparison
of 25 substitutions at 10 positions in the RSV conserved motif argues
against this possibility. Most of the replacements destroyed virus
infectivity, although either of two lethal phenotypes was obtained
depending on the residue introduced. At most of the positions, one or
more replacements (generally the more conservative substitutions)
caused a severe replication defect without having any obvious effects
on virus assembly, budding, Gag-Pol and genome incorporation, or
protein processing. The mutant particles exhibited a defect in
endogenous viral DNA synthesis and showed increased sensitivity of the
core proteins to detergent, indicating that the mutations interfere with the formation and/or activity of the virion core. The distribution of these mutations across the MHR, with no evidence of clustering, suggests that the entire region is important for a critical postbudding function. In contrast, a second class of lethal substitutions (those
that destroyed virus assembly and release) consists of alterations that
are expected to cause severe effects on protein structure by disruption
either of the hydrophobic core of the CA carboxyl-terminal domain or of
the hydrogen bond network that stabilizes the domain. We suggest that
this duality of phenotypes is consistent with a role for the MHR in the
maturation process that links the two parts of the life cycle.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.1.242-250.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Viral DNA Synthesis Defects in Assembly-Competent
Rous Sarcoma Virus CA Mutants
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, The Pennsylvania State University College of Medicine, 500 University Dr., P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-3528. Fax: (717) 531-6522. E-mail:
rcraven{at}psu.edu.
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