       Document 0387
 DOCN  M9620387
 TI    Processing of the envelope glycoprotein gp160 in immunotoxin-resistant
       cell lines chronically infected with human immunodeficiency virus type
       1.
 DT    9602
 AU    Duensing TD; Fang H; Dorward DW; Pincus SH; Laboratory of Microbial
       Structure and Function, Rocky Mountain; Laboratories, National Institute
       of Allergy and Infectious; Diseases, Hamilton, Montana 59840, USA.
 SO    J Virol. 1995 Nov;69(11):7122-31. Unique Identifier : AIDSLINE
       MED/96013815
 AB    We describe the isolation and characterization of variant cell lines
       which are chronically infected with the human immunodeficiency virus
       (HIV) and resistant to the action of immunotoxins directed against the
       HIV envelope protein. These variants all produce normal levels of HIV
       proteins, budding virions, and the envelope protein precursor gp160. Two
       of the variants, 10E and 11E, contain a mutation within the env gene
       which results in the production of a truncated precursor and altered
       processing and transport of the protein to the cell surface. Variants B9
       and G4 are defective in gp160 cleavage and do not efficiently transport
       the envelope protein to the cell surface. There are no mutations in the
       expressed viruses of B9 and G4. These cell lines express higher levels
       of CD4 protein and mRNA than H9/NL4-3. Thus, 10E, 11E, B9, and G4 have
       escaped immunotoxin action by downmodulating the envelope protein from
       their cell surfaces. None of these variants produce infectious HIV. Two
       other immunotoxin-resistant variants, E9-3 and 41-17, produce normal
       levels of gp160, efficiently transport the cleaved and processed
       subunits to the cell surface, and secrete infectious HIV. These studies
       identify alterations in gp160 processing that underscore the importance
       of the relationship between HIV and the cell that it infects.
 DE    Antigens, CD/BIOSYNTHESIS  Antigens, CD4/BIOSYNTHESIS  Cell
       Division/DRUG EFFECTS  Cell Line  Comparative Study  Dose-Response
       Relationship, Drug  Drug Resistance  Gene Products, env/*BIOSYNTHESIS
       Genes, env  Hela Cells  Human  HIV-1/GENETICS/*PHYSIOLOGY/ULTRASTRUCTURE
       Immunotoxins/*TOXICITY  Microscopy, Electron, Scanning  Protein
       Precursors/*BIOSYNTHESIS  *Protein Processing, Post-Translational  RNA,
       Messenger/ANALYSIS/BIOSYNTHESIS  Variation (Genetics)
       Virion/GENETICS/PHYSIOLOGY/ULTRASTRUCTURE  JOURNAL ARTICLE

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

