A conditionally replicating HIV-1 vector interferes with wild-type HIV-1 replication and spread.
Defective-interfering viruses are known to modulate virus pathogenicity. We describe conditionally replicating HIV-1 (crHIV) vectors that interfere with wild-type HIV-1 (wt-HIV) replication and spread. crHIV vectors are defective-interfering HIV genomes that do not encode viral proteins and replicate only in the presence of wt-HIV helper virus. In cells that contain both wt-HIV and crHIV genomes, the latter are shown to have a selective advantage for packaging into progeny virions because they contain ribozymes that cleave wt-HIV RNA but not crHIV RNA. A crHIV vector containing a triple anti-U5 ribozyme significantly interferes with wt-HIV replication and spread. crHIV vectors are also shown to undergo the full viral replicative cycle after complementation with wt-HIV helper-virus. The application of defective interfering crHIV vectors may result in competition with wt-HIVs and decrease pathogenic viral loads in vivo.
Dropulić
B
B
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. dropulic@welchlink.welch.jhu.edu
Hĕrmánková
M
M
Pitha
P M
PM
D002460:Cell Line; D003673:Defective Viruses; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016337:RNA, Catalytic / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D014762:Viral Interference; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
D016337:RNA, Catalytic; D012367:RNA, Viral