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M9490423.TXT
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1994-09-19
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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).