Document 0098
 DOCN  M9460098
 TI    Spontaneous substitutions in the vicinity of the V3 analog affect cell
       tropism and pathogenicity of simian immunodeficiency virus.
 DT    9404
 AU    Hirsch VM; Martin JE; Dapolito G; Elkins WR; London WT; Goldstein S;
       Johnson PR; Immunodeficiency Viruses Section, National Institute of
       Allergy; and Infectious Diseases, Rockville, MD 20852.
 SO    J Virol. 1994 Apr;68(4):2649-61. Unique Identifier : AIDSLINE
       GENBANK/U04991
 AB    Simian immunodeficiency virus (SIV) exists within tissues of infected
       macaques as a mixture of diverse genotypes. The goal of this study was
       to investigate the biologic significance of this variation in terms of
       cellular tropism and pathogenicity. PCR was used to amplify and clone
       3'-half genomes from the spleen of an immunodeficiency SIV-infected
       pig-tailed macaque (Macaca nemestrina). Eight infectious clones were
       generated by ligation of respective 3' clones into a related SIVsm 5'
       clone, and virus stocks were generated by transient transfection. Four
       of these viruses were infectious for macaque peripheral blood
       mononuclear cells (PBMC) or monocyte-derived macrophages (MDM). Three
       viruses with distinct tropism for macaque PBMC or MDM were tested for in
       vivo infectivity and pathogenicity. The ability of these three viruses
       to infect PBMC and macrophages correlated with differences in
       infectivity and pathogenicity. Thus, a virus that was infectious for
       both PBMC and MDM was highly infectious for macaques and induced AIDS in
       half of the inoculated animals. In contrast, virus that was less
       infectious for PBMC and not infectious for MDM induced only transient
       viremia. Finally, a virus that was not infectious for either primary
       cell type did not infect macaques. Chimeric clones exchanging portions
       of the envelope gene of the 62A and smH4 molecular clones and a series
       of point mutants were used to map the determinant of tropism to a
       60-amino-acid region of gp120 encompassing the V3 analog of SIV.
       Naturally occurring mutations within this region were critical for
       determining tropism and, as a result, pathogenicity of these SIVsm
       clones.
 DE    Amino Acid Sequence  Animal  Base Sequence  Chimeric Proteins  Cloning,
       Molecular  Comparative Study  Cytopathogenic Effect, Viral  DNA
       Mutational Analysis  HIV Envelope Protein gp120/*GENETICS  Leukocytes,
       Mononuclear/MICROBIOLOGY  Macaca  Macrophages/MICROBIOLOGY  Molecular
       Sequence Data  Point Mutation  Polymerase Chain Reaction  Precipitin
       Tests  Sequence Homology, Amino Acid  Simian Acquired Immunodeficiency
       Syndrome/*MICROBIOLOGY  Spleen/MICROBIOLOGY
       SIV/*GENETICS/*PATHOGENICITY  Transfection  JOURNAL ARTICLE

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