Specific properties of shRNA-mediated CCR5 downregulation that enhance the inhibition of HIV-1 infection in combination with shRNA targeting HIV-1 rev

Cardona Gomez, Maria EugeniaLinköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Karolinska Inst, Sweden (author)

Funding Agencies|Corporacion para el Desarrollo de la Ciencia y la Tecnologia
Treatment with RNAi against HIV-1 transcripts efficiently inhibits viral replication but induces selection of escape mutants; therefore, the CCR5 coreceptor was suggested as an additional target. Blocking viral and host transcripts improved the antiviral effect. We have used short hairpin RNA (shRNA) targeting the human CCR5 (shCCR5) or the HIV-1 rev (shRev) transcripts to demonstrate distinctive properties of anti-CCR5 shRNA: shCCR5 induced more sustained protection than shRev; partial reduction in CCR5 expression substantially decreased HIV-1 infection, and shCCR5 performed better than shRev in the mixed shRNA-treated and untreated cultures. These observations indicate that CCR5 inhibitors should be conveniently included in HIV-1 gene silencing treatment schedules when only a certain cell fraction is protected to further reduce endogenous virus in a properly ART-treated HIV-1 infected individual.

Hinkula, Jorma,1958-Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten(Swepub:liu)jorhi40 (author)
Gustafsson, KristinKarolinska Inst, Sweden (author)
Christensson, BirgerKarolinska Univ Hosp, Sweden (author)
Wahren, BrittaKarolinska Institutet (author)
Mohamed, Abdalla J.Karolinska Inst, Sweden (author)
Smith, C. I. EdvardKarolinska Institutet (author)
Arteaga, H. JoseKarolinska Inst, Sweden; Univ Ind Santander, Colombia (author)
Linköpings universitetAvdelningen för molekylär medicin och virologi (creator_code:org_t)

By the author/editor: Cardona Gomez, M ...; Hinkula, Jorma, ...; Gustafsson, Kris ...; Christensson, Bi ...; Wahren, Britta; Mohamed, Abdalla ...; show more...; Smith, C. I. Edv ...; Arteaga, H. Jose; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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