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M9480505.TXT
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1994-08-20
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Document 0505
DOCN M9480505
TI Role of the major homology region of human immunodeficiency virus type 1
in virion morphogenesis.
DT 9410
AU Mammano F; Ohagen A; Hoglund S; Gottlinger HG; Division of Human
Retrovirology, Data-Farber Cancer Institute,; Boston, Massachusetts.
SO J Virol. 1994 Aug;68(8):4927-36. Unique Identifier : AIDSLINE
MED/94309156
AB Retroviral capsid (CA) proteins contain a uniquely conserved stretch of
20 amino acids which has been named the major homology region (MHR). To
examine the role of this region in human immunodeficiency virus type 1
morphogenesis and replication, four highly conserved positions in the
MHR were individually altered by site-directed mutagenesis. Conservative
substitution of two invariant residues (glutamine 155 and glutamic acid
159) abolished viral replication and significantly reduced the
particle-forming ability of the mutant gag gene products. Conservative
substitution of the third invariant residue in the MHR (arginine 167) or
of an invariably aromatic residue (tyrosine 164) had only a moderate
effect. However, removal of the extended side chains of these amino
acids by substitution with alanine prevented viral replication and
affected virion morphogenesis. The replacement of tyrosine 164 with
alanine substantially impaired viral particle production. By contrast,
the substitution of arginine 167 with alanine had only a two- to
threefold effect on particle yield but led to the formation of aberrant
core structures. The MHR mutant which were severely defective for
particle production had a dominant negative effect on particle formation
by the wild-type Gag product. The role of the MHR in the incorporation
of the Gag-Pol precursor was examined by expressing the Gag and Gag-Pol
polyproteins individually from separate plasmids. Only when the two
precursor polyproteins were coexpressed did processed Gag and Pol
products appear in the external medium. The appearance of these products
was unaffected or only moderately affected by substitutions in the MHR
of the Gag-Pol precursor, suggesting that the mutant Gag-Pol precursors
were efficiently incorporated into viral particles. The results of this
study indicate that specific residues within the MHR are required both
for human immunodeficiency virus type 1 particle assembly and for the
correct assembly of the viral core. However, mutant Gag and Gag-Pol
polyproteins with substitutions in the MHR retained the ability to
interact with wild-type Gag protein.
DE Amino Acid Sequence Base Sequence Capsid/GENETICS/*PHYSIOLOGY Cell
Line Conserved Sequence DNA, Viral Evolution Gene Products,
gag/GENETICS Hela Cells Human
HIV-1/*GENETICS/PHYSIOLOGY/ULTRASTRUCTURE Molecular Sequence Data
Morphogenesis Mutagenesis, Site-Directed Sequence Homology Support,
Non-U.S. Gov't Support, U.S. Gov't, P.H.S.
Virion/PHYSIOLOGY/ULTRASTRUCTURE *Virus Replication/GENETICS JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).