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Journal of Virology, August 2003, p. 8524-8531, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8524-8531.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Human Cellular Nucleic Acid-Binding Protein Zn2+ Fingers Support Replication of Human Immunodeficiency Virus Type 1 When They Are Substituted in the Nucleocapsid Protein

Connor F. McGrath,1 James S. Buckman,2 Tracy D. Gagliardi,2 William J. Bosche,2 Lori V. Coren,2 and Robert J. Gorelick2*

Developmental Therapeutics Program—Target Structure Based Drug Discovery Group,1 AIDS Vaccine Program, Science Applications International Corporation—Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland 21702-12012

Received 16 December 2002/ Accepted 8 May 2003

A family of cellular nucleic acid binding proteins (CNBPs) contains seven Zn2+ fingers that have many of the structural characteristics found in retroviral nucleocapsid (NC) Zn2+ fingers. The sequence of the NH2-terminal NC Zn2+ finger of the pNL4-3 clone of human immunodeficiency virus type 1 (HIV-1) was replaced individually with sequences from each of the seven fingers from human CNBP. Six of the mutants were normal with respect to protein composition and processing, full-length genomic RNA content, and infectivity. One of the mutants, containing the fifth CNBP Zn2+ finger (CNBP-5) packaged reduced levels of genomic RNA and was defective in infectivity. There appear to be defects in reverse transcription in the CNBP-5 infections. Models of Zn2+ fingers were constructed by using computational methods based on available structural data, and atom-atom interactions were determined by the hydropathic orthogonal dynamic analysis of the protein method. Defects in the CNBP-5 mutant could possibly be explained, in part, by restrictions of a set of required atom-atom interactions in the CNBP-5 Zn2+ finger compared to mutant and wild-type Zn2+ fingers in NC that support replication. The present study shows that six of seven of the Zn2+ fingers from the CNBP protein can be used as substitutes for the Zn2+ finger in the NH2-terminal position of HIV-1 NC. This has obvious implications in antiviral therapeutics and DNA vaccines employing NC Zn2+ finger mutants.

* Corresponding author. Mailing address: AIDS Vaccine Program, Science Applications International Corporation—Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702-1201. Phone: (301) 846-5980. Fax: (301) 846-7119. E-mail: gorelick{at}ncifcrf.gov.

Journal of Virology, August 2003, p. 8524-8531, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8524-8531.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chatel-Chaix, L., Abrahamyan, L., Frechina, C., Mouland, A. J., DesGroseillers, L. (2007). The Host Protein Staufen1 Participates in Human Immunodeficiency Virus Type 1 Assembly in Live Cells by Influencing pr55Gag Multimerization. J. Virol. 81: 6216-6230 [Abstract] [Full Text]  
  • Thomas, J. A., Ott, D. E., Gorelick, R. J. (2007). Efficiency of Human Immunodeficiency Virus Type 1 Postentry Infection Processes: Evidence against Disproportionate Numbers of Defective Virions. J. Virol. 81: 4367-4370 [Abstract] [Full Text]  


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