Characterization of human immunodeficiency virus (HIV)-2 vector mobilization by HIV-1.
Conditionally replicating human immunodeficiency virus type 2 (crHIV-2) vectors can compete with HIV-1 for packaging in HIV-1-infected cells, indicating that the mobilization of vectors could selectively target as well as protect reservoirs susceptible to HIV-1 infection. The incorporation of HIV-1-specific antiviral transgenes in crHIV-2 vectors, although increasing the direct antiviral effect, may decrease mobilization and transmission to surrounding cells. To investigate how HIV-1-specific catalytic RNA cassettes (ribozymes) affect this balance between antiviral activity and mobilization, crHIV-2 vectors shown to display anti-HIV-1 activity were packaged by HIV-2 and used to transduce cells previously infected with HIV-1 or to transduce uninfected cells that were subsequently challenged with HIV-1. Vector mobilization was greater when HIV-1-infected cells were transduced with vector than when transduced cells were infected with HIV-1, and approximately 3-fold lower vector production was observed in cultures transduced with vectors expressing anti-HIV-1 ribozymes. Vector and antiviral effects could be transferred to new cultures by passaging supernatants to fresh cultures. No evidence of recombination with HIV-1 was observed. Vector mobilization and protection from HIV-1 infection were also demonstrated in human peripheral blood mononuclear cells. These data suggest that strategies employing vector mobilization for HIV-1 gene therapy should use vectors with maximal antiviral potency, despite resulting reductions in mobilization of the vector.
Morris
Kevin V
KV
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA. kmorris@scripps.edu
Looney
David J
DJ
D001483:Base Sequence; D015316:Genetic Therapy; D005822:Genetic Vectors; D015658:HIV Infections / Q000235:genetics / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D015498:HIV-2 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016337:RNA, Catalytic / Q000235:genetics*; D012367:RNA, Viral; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D014762:Viral Interference / Q000235:genetics; D014779:Virus Replication
D016337:RNA, Catalytic; D012367:RNA, Viral