High frequency of defective nef alleles in a long-term survivor with nonprogressive human immunodeficiency virus type 1 infection

Mariani, R., Kirchhoff, F., Greenough, T. C., Sullivan, J. L., Desrosiers, R. C., Skowronski, J. (November 1996) High frequency of defective nef alleles in a long-term survivor with nonprogressive human immunodeficiency virus type 1 infection. Journal of Virology, 70 (11). pp. 7752-64. ISSN 0022-538X

URL: http://www.ncbi.nlm.nih.gov/pubmed/8892896

Abstract

A large number of nef alleles were obtained from peripheral blood mononuclear cells (PBMC) of four long-term nonprogressing survivors of human immunodeficiency virus type 1 (HIV-1) infection and from five individuals with progressive HIV-1 infection. These primary nef alleles were characterized by DNA sequence analysis and for their ability to downregulate CD4 surface expression. Intact nef open reading frames that directed the expression of Nef protein were recovered from all of the individuals. Most of the Nef proteins derived from three of four individuals with nonprogressive infection and from all five individuals with progressive infection were functional as judged by their ability to induce a decrease in surface CD4 expression. In contrast, one individual with nonprogressive HIV-1 infection yielded an unusually high frequency of disrupted nef open reading frames and Nef proteins defective for CD4 downregulation. Approximately 70% of the nef clones obtained from the PBMC of this individual at eight time points over a 12-year period were disrupted or defective for CD4 downregulation. While functional Nef proteins were demonstrated early in the course of infection (1983), functional nef alleles have surprisingly not come to predominate over time in PBMC DNA in this individual.

Item Type: Paper
Uncontrolled Keywords: Alleles Amino Acid Sequence Antigens, CD4/metabolism DNA, Viral Follow-Up Studies Gene Frequency Genes, nef HIV Infections/ virology HIV-1/ genetics/metabolism Humans Jurkat Cells Molecular Sequence Data Mutation Phylogeny Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Sequence Homology, Amino Acid Survivors
Subjects: bioinformatics > genomics and proteomics > design > amino acid design
diseases & disorders > viral diseases > HIV
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:
Communities: CSHL labs > Skowronski lab
Depositing User: Kathleen Darby
Date: November 1996
Date Deposited: 13 May 2014 16:50
Last Modified: 13 May 2014 16:50
PMCID: PMC190845
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30088

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