Document 0423
 DOCN  M9490423
 TI    Biological, molecular, and structural analysis of a cytopathic variant
       from a molecularly cloned simian immunodeficiency virus.
 DT    9411
 AU    LaBranche CC; Sauter MM; Haggarty BS; Vance PJ; Romano J; Hart TK;
       Bugelski PJ; Hoxie JA; Hematology-Oncology Division, Hospital of the
       University of; Pennsylvania, Philadelphia 19104.
 SO    J Virol. 1994 Sep;68(9):5509-22. Unique Identifier : AIDSLINE
       MED/94335063
 AB    Some isolates of simian immunodeficiency virus (SIV) have been shown to
       infect Sup-T1 cells with slow kinetics and in the absence of cytopathic
       effects, including cell fusion or CD4 down-modulation (J. A. Hoxie, B.
       S. Haggarty, S. Bonser, J. Rackowski, H. Shan, and P. Kanki, J. Virol.
       62:2557-2568, 1988). In the present study, we describe the isolation and
       characterization of a SIVmac variant, derived from the BK28 infectious
       molecular clone, that became highly cytopathic for Sup-T1 cells. This
       variant, termed CP-MAC, exhibited a number of differences from BK28,
       including (i) an altered tropism which largely restricted its host range
       to Sup-T1 cells, (ii) the ability to induce cell fusion and CD4
       down-modulation, and (iii) a highly stable interaction of its external
       (SU) and transmembrane (TM) envelope glycoproteins. In addition, a
       marked increase in the level of surface envelope glycoproteins was
       observed both on CP-MAC-infected cells and on virions. The CP-MAC env
       gene was PCR amplified from infected cells, and sequence analysis
       identified five amino acid changes in SU and six in TM compared with
       BK28. The introduction of these changes into BK28 was shown to fully
       reconstitute the biological and morphological properties of CP-MAC. The
       limited number of mutations in CP-MAC should enable the molecular
       determinants to be more precisely defined and help to identify the
       underlying mechanisms responsible for the striking biological and
       structural alterations exhibited by this virus.
 DE    Amino Acid Sequence  Base Sequence  Cloning, Molecular  Comparative
       Study  Cytopathogenic Effect, Viral  DNA Primers/CHEMISTRY  Gene
       Products, env/*PHYSIOLOGY  Genes, env  Molecular Sequence Data  Sequence
       Alignment  Sequence Homology, Amino Acid  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  SIV/GENETICS/*PATHOGENICITY/ULTRASTRUCTURE
       Virion/CHEMISTRY  Virus Replication  JOURNAL ARTICLE

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