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).