Document 0084
 DOCN  M9590084
 TI    The glycosylation of human immunodeficiency virus type 1 transmembrane
       glycoprotein (gp41) is important for the efficient intracellular
       transport of the envelope precursor gp160.
 DT    9509
 AU    Fenouillet E; Jones IM; Institute of Virology, NERC, Oxford, UK.
 SO    J Gen Virol. 1995 Jun;76 ( Pt 6):1509-14. Unique Identifier : AIDSLINE
       MED/95302048
 AB    The role of the glycans of the human immunodeficiency virus type 1
       transmembrane glycoprotein (gp41) in the intracellular events of Env
       precursor (gp160) biosynthesis has been examined by the use of a mutant
       gp160 in which the cluster of conserved glycosylation sites within the
       gp41 domain (Asn-621, -630 and 642) has been mutated. Expression of the
       wild-type and mutant forms of gp160 in BHK-21 cells using recombinant
       vaccinia viruses has shown that the kinetics of the events occurring in
       the endoplasmic reticulum (ER) were normal: both Env proteins had
       similar kinetics of disulphide bond formation, as determined by the
       acquisition of CD4-binding capability, and both had similar kinetics of
       oligomer formation. However, in contrast to the parental molecule,
       mutated gp160 displayed relatively slow transport from the cis to the
       medial Golgi where it was retained in the oligomeric state. Transport to
       the trans Golgi was impaired, as determined by the sensitivity of gp160
       to glycosidases. Cleavage of mutated gp160 at the gp120/gp41 junction
       was substantially reduced but this was apparently not due to the
       involvement of the gp41 glycosylation in the cleavage reaction by furin
       inasmuch as, in the baculovirus system, mutated gp160 could be cleaved
       when recombinant furin was co-expressed. The reduced cleavage in
       mammalian cells may thus reflect the impaired routing of mutated Env to
       the compartment where cleavage occurs. The glycan component of gp41 is,
       therefore, important for the efficient intracellular transport and
       processing of gp160. gp160 lacking gp41 carbohydrates is an additional
       example, among few others, of a protein lacking glycans that is arrested
       in the Golgi rather than the ER following its biosynthesis.
 DE    Amino Acid Sequence  Animal  Antigens, CD4/BIOSYNTHESIS/METABOLISM
       Asparagine  Cell Line  Conserved Sequence  Gene Products,
       env/BIOSYNTHESIS/*METABOLISM  Genetic Vectors  Glycosylation  Golgi
       Apparatus/METABOLISM  Hamsters  HIV Envelope Protein
       gp41/BIOSYNTHESIS/*METABOLISM  HIV-1/*METABOLISM  Kidney  Kinetics
       Mutagenesis, Site-Directed  Protein Precursors/BIOSYNTHESIS/*METABOLISM
       *Protein Processing, Post-Translational  Recombinant
       Proteins/BIOSYNTHESIS/METABOLISM  Subtilisins/BIOSYNTHESIS  Support,
       Non-U.S. Gov't  Transfection  Vaccinia Virus  JOURNAL ARTICLE

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