Previous Article | Next Article ![]()
Journal of Virology, October 2001, p. 9357-9366, Vol. 75, No. 19
Laboratory of Molecular Genetics, National
Institute of Child Health and Human
Development,1 and Laboratory of
Molecular Microbiology, National Institute of Allergy and Infectious
Diseases,2 Bethesda, Maryland 20892, and
HIV Drug Resistance Program, Frederick Cancer Research and
Development Center, National Cancer Institute, Frederick, Maryland
217023
Received 21 March 2001/Accepted 23 June 2001
A group of conserved hydrophobic residues faces the interior of the
coiled-coil-like structure within the N-terminal domain of the human
immunodeficiency virus type 1 (HIV-1) capsid protein (CA). It has been
suggested that these residues are important for maintaining stable
structure and functional activity. To investigate this possibility, we
constructed two HIV-1 clones, in which Trp23 or Phe40 was changed to
Ala. We also constructed a third mutant, D51A, which has a mutation
that destroys a salt bridge between Pro1 and Asp51. All three mutants
are replication defective but produce virus particles. Mutant virions
contain all of the viral proteins, although the amount and stability of
CA are decreased and levels of virion-associated integrase are reduced.
The mutations do not affect endogenous reverse transcriptase activity;
however, the mutants are blocked in their ability to initiate reverse
transcription in infected cells and no minus-strand strong-stop DNA is
detected. The defect in reverse transcription is associated with
striking defects in the morphology of mutant virus cores, as determined by transmission electron microscopy. Our data indicate that the mutations made in this study disrupt CA structure and prevent proper
maturation of virus cores. We propose that this results in a defect in
core stability or in an early postentry event preceding reverse transcription.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.19.9357-9366.2001
Human Immunodeficiency Virus Type 1 N-Terminal Capsid Mutants
That Exhibit Aberrant Core Morphology and Are Blocked in Initiation
of Reverse Transcription in Infected Cells
*
Corresponding author. Mailing address: Laboratory of
Molecular Genetics, NICHD, Building 6B, Room 216, NIH, Bethesda, MD
20892-2780. Phone: (301) 496-1970. Fax: (301) 496-0243. E-mail:
jlevin{at}mail.nih.gov.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|