Human Cellular Nucleic Acid-Binding Protein Zn2+Fingers Support Replication of Human Immunodeficiency Virus Type 1 When They Are Substituted in the Nucleocapsid Protein
Open Access
- 1 August 2003
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 77 (15) , 8524-8531
- https://doi.org/10.1128/jvi.77.15.8524-8531.2003
Abstract
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.Keywords
This publication has 79 references indexed in Scilit:
- Human Immunodeficiency Virus Type 1 Nucleocapsid Zn 2+ Fingers Are Required for Efficient Reverse Transcription, Initial Integration Processes, and Protection of Newly Synthesized Viral DNAJournal of Virology, 2003
- Mpe1, a Zinc Knuckle Protein, Is an Essential Component of Yeast Cleavage and Polyadenylation Factor Required for the Cleavage and Polyadenylation of mRNAMolecular and Cellular Biology, 2001
- Regulation of Mouse Colony-Stimulating Factor-1 Gene Promoter Activity by AP1 and Cellular Nucleic Acid-Binding ProteinDNA and Cell Biology, 1998
- Involvement of the Xenopus laevis Ro60 autoantigen in the alternative interaction of La and CNBP proteins with the 5′UTR of L4 ribosomal protein mRNA † 1 †In previous papers the numbering of Xenopus ribosomal proteins followed the system introduced in our first study (Pierandrei-Amaldi & Beccari, 1980). The large amount of sequencing data now accumulated in many species allows adoption of the rat system for a unified nomenclature (Wool et al., 1990). Thus, the Xenopus r-protein that we previously designated L1 is here identified as L4, L14 as L18 and S1 as S3 (Amaldi et al., 1995). 1Edited by M. YanivJournal of Molecular Biology, 1998
- Use of 3D QSAR Methodology for Data Mining the National Cancer Institute Repository of Small Molecules: Application to HIV-1 Reverse Transcriptase InhibitionMethods, 1998
- Mouse Cellular Nucleic Acid Binding Proteins: A Highly Conserved Family Identified by Genetic Mapping and SequencingGenomics, 1994
- Phosphorescence and Optically Detected Magnetic Resonance Investigation of the Binding of the Nucleocapsid Protein of the Human Immunodeficiency Virus Type 1 and Related Peptides to RNABiochemistry, 1994
- KEY, LOCK, and LOCKSMITH: Complementary hydropathic map predictions of drug structure from a known receptor-receptor structure from known drugsJournal of Molecular Graphics, 1992
- Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDSScience, 1984