M. Shahabuddin et As. Khan, Inhibition of human immunodeficiency virus type 1 by packageable, multigenic antisense RNA, ANTISENSE N, 10(3), 2000, pp. 141-151
Viral-based vectors can provide an efficient delivery mechanism for stable
expression of antisense RNA. To enhance and propagate the antiviral effect
of antisense RNA, two novel human immunodeficiency virus type 1 (HIV-1)-bas
ed vector DNAs, designated as pMAG7 and pMAG19, were constructed which cont
ained HIV-1 cis-acting packaging elements and produced multigenic HIV-1 ant
isense RNA that could target the entire pal, env, vif, vpu, vpr, rev, and t
at and portions of gag and nef. The two DNAs were identical except that pMA
G19 had additional gag coding sequences, Cotransfection of pMAG DNA and inf
ectious, cloned HIV-1 DNA in 293 cells inhibited virus production (81%-98%
reduction in reverse transcriptase activity) of various T cell-tropic and m
acrophage-tropic clade B isolates, such as NL4-3, YU-2, and JR-CSF, In addi
tion, virion-associated pMAG antisense RNA was detected in residual virus p
articles produced by pNL4-3 in the presence of pMAG7 DNA, and the antisense
sequences were stably transferred by infection of 174 x CEM cells. The res
ults suggest that pMAG DNA may confer broad protection against HIV-1 by red
ucing initial virus burden due to antisense RNA and subsequent virus spread
by propagation of antisense sequences along with wild-type virus.