Document 0251
 DOCN  M94A0251
 TI    Persistent infection of MT-4 cells by human immunodeficiency virus type
       1 becomes increasingly likely with in vitro serial passage of wild-type
       but not nef mutant virus.
 DT    9412
 AU    Nishino Y; Nakaya T; Fujinaga K; Kishi M; Azuma I; Ikuta K; Institute of
       Immunological Science, Hokkaido University, Sapporo,; Japan.
 SO    J Gen Virol. 1994 Sep;75 ( Pt 9):2241-51. Unique Identifier : AIDSLINE
       MED/94358722
 AB    Our previous studies have shown that human immunodeficiency virus type 1
       (HIV-1), with mutations in accessory genes such as vif, vpr or vpu, can
       generate persistent infection of MT-4 cells, whereas infection by
       wild-type or nef mutant HIV-1 causes extensive cell death. The
       possibility of generating a naturally attenuated form of HIV-1 with
       reduced cytopathogenicity in MT-4 cells was examined by in vitro serial
       passage of the wild-type and a nef mutant form of HIV-1, each derived
       from the infectious molecular clone pNL432. The ability to cause
       persistent infection was observed after four passages of wild-type HIV-1
       with the frequency of persistence becoming progressively higher with
       serial passage. In contrast, persistent infection was not observed even
       after 50 passages of the nef mutant virus. Sequence analysis of the
       accessory gene loci in genomes recovered from the persistent infections
       caused by passaged virus revealed mutations in vif and vpr, but not in
       vpu. The processing of the Env precursor to mature forms was not
       modified in any of the passages of either wild-type or nef mutant HIV-1.
       However, when compared with acute infections caused by similarly
       passaged virus of both wild-type and nef mutant HIV-1, persistent
       infections by passaged wild-type HIV-1 showed a significant decrease in
       the cell surface expression and function of Env. Cell surface CD4 was
       only partially down-regulated on cells acutely infected with the
       passaged viruses, whereas on cells persistently infected with passaged
       wild-type HIV-1 it was completely down-regulated. These results suggest
       that, during serial passage of HIV-1, mutations accumulate at least in
       the accessory genes vif and vpr in parallel with a lesser interaction
       between cell surface Env and CD4 molecules, and lead to the generation
       of less cytopathogenic viruses capable of persistent infection. Our
       results also suggest an important role for the nef gene product in the
       generation of HIV-1 strains that are less cytopathogenic.
 DE    Amino Acid Sequence  Antigens, CD/BIOSYNTHESIS  Antigens,
       CD4/BIOSYNTHESIS  Base Sequence  Cell Membrane/METABOLISM/ULTRASTRUCTURE
       Clone Cells  Comparative Study  DNA Primers  Gene Products,
       env/BIOSYNTHESIS  *Genes, nef  Genes, vif  Genes, vpr  Genes, vpu  Giant
       Cells  Human  HIV Envelope Protein gp120/BIOSYNTHESIS
       HIV-1/GENETICS/*PHYSIOLOGY/PATHOGENICITY  Kinetics  Molecular Sequence
       Data  *Mutation  Polymerase Chain Reaction  Reverse
       Transcriptase/METABOLISM  Support, Non-U.S. Gov't  T-Lymphocytes  Time
       Factors  Viral Proteins/BIOSYNTHESIS/CHEMISTRY  *Virus Replication
       JOURNAL ARTICLE

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