       Document 0518
 DOCN  M9630518
 TI    Biological characterization of nef in long-term survivors of human
       immunodeficiency virus type 1 infection.
 DT    9603
 AU    Huang Y; Zhang L; Ho DD; Aaron Diamond AIDS Research Center, New York
       University School of; Medicine, New York 10016, USA.
 SO    J Virol. 1995 Dec;69(12):8142-6. Unique Identifier : AIDSLINE
       MED/96079075
 AB    We have previously shown that there were no gross deletions or obvious
       sequence abnormalities within nef of human immunodeficiency virus type 1
       (HIV-1) in the 10 long-term survivors studied (Y. Huang, L. Zhang, and
       D. D. Ho, J. Virol. 69:93-100, 1995). Here we extend our study to
       examine these nef alleles in a functional context. Using a new
       technique, termed site-directed gene replacement, we have precisely
       replaced the nef of an infectious molecular clone, HIV-1HXB2, with nef
       alleles derived from 10 long-term survivors as well as from a patient
       with AIDS. The replication properties of these chimeric viruses
       demonstrated that the nef alleles derived from long-term survivors
       neither significantly increased nor decreased viral replication,
       compared with the nef allele of Nef+ HIV-1HXB2 and that derived from a
       patient with AIDS. However, Nef+ viruses always replicated faster than
       virus lacking nef. Moreover, single-cell infection analysis by the MAGI
       assay showed that these chimeric viruses, as well as Nef+ HIV-1HXB2,
       were more infectious than Nef- HIV-1HXB2 was. Therefore, we conclude
       that the genotypic and phenotypic features of nef are not likely to
       account for the nonprogression of HIV-1 infection in the 10 cases
       studied, unless the function of the nef gene in vivo is not accurately
       reflected by the in vitro assays we used.
 DE    Acquired Immunodeficiency Syndrome/PHYSIOPATHOLOGY/*VIROLOGY  Alleles
       Amino Acid Sequence  Cells, Cultured  Chimera  Comparative Study
       Follow-Up Studies  Gene Deletion  Gene Products, nef/*CHEMISTRY/GENETICS
       *Genes, nef  Human  HIV Seropositivity/*PHYSIOPATHOLOGY/*VIROLOGY
       HIV-1/*GENETICS/ISOLATION & PURIF/PHYSIOLOGY  Kinetics
       Lymphocytes/IMMUNOLOGY/VIROLOGY  Molecular Sequence Data  Mutagenesis,
       Site-Directed  Sequence Homology, Amino Acid  Support, U.S. Gov't,
       P.H.S.  Time Factors  Virus Replication  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

