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M94A3332.TXT
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1994-10-25
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Document 3332
DOCN M94A3332
TI Restricted replication of SIVMAC239 in macrophages.
DT 9412
AU Mori K; Desrosiers R; New England Regional Primate Research Center,
Harvard Medical; School, Southborough, MA.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):10 (abstract no. 013A). Unique
Identifier : AIDSLINE ICA10/94369243
AB An infectious, pathogenic, molecular clone of SIVmac239 causes AIDS and
death in rhesus monkeys in a time frame suitable for laboratory
investigation. This cloned SIVmac239 replicates poorly in primary
macrophage cultures from rhesus monkeys. Variants with high replicative
capacity for macrophages emerge in about 40% of rhesus monkeys that die
with AIDS following infection with this cloned virus. Changes of
67V-->M, 176K-->E, and 382G-->R within envelope were shown to be
primarily responsible for the markedly increased replicative capacity
for macrophages in three independent cases that were examined.
Measurement of early events demonstrated that restricted replication of
SIVmac239 in macrophages was not due to initial restricted entry. This
was somewhat surprising since the restricted replication was
env-determined. SIVmac239 RNA levels increased normally for the first 72
hours in macrophages but then subsequently declined. Careful inspection
of the kinetics of virus production suggested that SIVmac239 is produced
in normal amounts for the initial 2-4 days following infection but that
production subsequently declines. After 2 or more days of infection,
macrophages were found to restrict entry and reverse transcription of
SIVmac239 but not of the variants with high replicative capacity for
macrophages. These results suggest that variants with high replicative
capacity for macrophages are insensitive to an antiviral state that
develops in macrophage cultures following infection.
DE Animal Cells, Cultured Macaca mulatta/*MICROBIOLOGY Macrophages RNA,
Viral Simian Acquired Immunodeficiency Syndrome/*MICROBIOLOGY
SIV/*GROWTH & DEVELOPMENT/GENETICS Transcription, Genetic Viral
Envelope Proteins *Virus Replication MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).