Virology. 1997 Jun 9;232(2):291-9. Unique Identifier : AIDSLINE
Lentiviruses control virion production via posttranscriptional
regulation mediated by the viral Rev protein. In this study, we
demonstrate that the Rev regulation of SIVmac239 can be replaced by the
presence of the cis-acting transport element (CTE) of the type D simian
retroviruses 1 (SRV-1). To avoid the possibility of generating
revertants, the Rev-Independent SIV clones have both rev and the Rev
responsive element (RRE) destroyed by multiple point mutations that do
not affect the overlapping tat and env open reading frames. Virus stocks
generated from these Rev-independent SIV molecular clones can infect and
can be propagated in rhesus peripheral blood mononuclear cells (PBMCs).
Therefore, the Rev/RRE system of SIVmac239 can be replaced by the SRV-1
CTE as previously shown for HIV-1. In both rhesus and human primary
cells, the replicative capacity of the Rev-independent SIV is 10- to
20-fold lower than that of the wild-type virus. Rhesus PBMC-derived
virus stocks of the Rev-independent SIV have lower infectivity.
Interestingly, in CEM x 174 cells, no difference in replicative capacity
between wild-type and Rev-independent SIV has been observed. The
Rev-independent SIV has a stable genotype after several passages in
primary cells. The availability of such Rev-Independent viruses will
allow the study of the role of Rev in pathogenesis and the potential
generation of attenuated SIV strains.
*Gene Expression Regulation, Viral *Gene Products, rev/GENETICS
*Leukocytes, Mononuclear/VIROLOGY *SIV/GENETICS *SIV/PHYSIOLOGY