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M9620387.TXT
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1996-02-26
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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).