Home LiteratureArticle Details
PMID: 8855316 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A conditionally replicating HIV-1 vector interferes with wild-type HIV-1 replication and spread.

Dropulić B, Hĕrmánková M, Pitha PM

Abstract

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.

MeSH Terms
Cell Line Defective Viruses Genetic Vectors HIV-1/genetics Humans RNA, Catalytic/metabolism RNA, Viral/metabolism Viral Interference Virion/metabolism Virus Replication
Chemicals
RNA, Catalytic RNA, Viral
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dropulić B
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. dropulic@welchlink.welch.jhu.edu
Hĕrmánková M
Pitha P M
References (45)
45 references, click to expand
  1. Effects of defective interfering viruses on virus replication and pathogenesis in vitro and in vivo.
    Adv Virus Res. 1991;40:181-211 PMID: 1957718
  2. Sequence requirements of the hammerhead RNA self-cleavage reaction.
    Biochemistry. 1990 Nov 27;29(47):10695-702 PMID: 1703005
  3. Human immunodeficiency virus vectors for inducible expression of foreign genes.
    J Virol. 1992 May;66(5):2731-9 PMID: 1560523
  4. Genetic diversity and evolution of retroviruses.
    Curr Top Microbiol Immunol. 1992;176:143-64 PMID: 1600751
  5. Small catalytic RNAs.
    Annu Rev Biochem. 1992;61:641-71 PMID: 1497321
  6. Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication.
    J Exp Med. 1992 Oct 1;176(4):1197-201 PMID: 1402661
  7. Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication--potential effectiveness against most presently sequenced HIV-1 isolates.
    Nucleic Acids Res. 1992 Sep 11;20(17):4581-9 PMID: 1408760
  8. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.
    Science. 1993 Mar 19;259(5102):1749-54 PMID: 8096089
  9. Downregulation of cell-surface CD4 expression by simian immunodeficiency virus Nef prevents viral super infection.
    J Exp Med. 1993 Jun 1;177(6):1561-6 PMID: 8098729
  10. Packaging of human immunodeficiency virus type 1 RNA requires cis-acting sequences outside the 5' leader region.
    J Virol. 1993 Jul;67(7):3997-4005 PMID: 8510213
  11. Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody.
    Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7889-93 PMID: 8356098
  12. Tethering ribozymes to a retroviral packaging signal for destruction of viral RNA.
    Science. 1993 Dec 3;262(5139):1566-9 PMID: 8248806
  13. Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations.
    J Biol Chem. 1994 Jan 28;269(4):2550-61 PMID: 8300583
  14. Human immunodeficiency virus type 1 mRNA expression in peripheral blood cells predicts disease progression independently of the numbers of CD4+ lymphocytes.
    Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1104-8 PMID: 7905630
  15. Analysis in human immunodeficiency virus type 1 vectors of cis-acting sequences that affect gene transfer into human lymphocytes.
    J Virol. 1994 Jun;68(6):3888-95 PMID: 7910642
  16. Gene therapy for human immunodeficiency virus infection: genetic antiviral strategies and targets for intervention.
    Hum Gene Ther. 1994 Aug;5(8):927-39 PMID: 7948142
  17. Nonviral and viral delivery of a human immunodeficiency virus protective gene into primary human T cells.
    Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11581-5 PMID: 7972106
  18. Viral dynamics in human immunodeficiency virus type 1 infection.
    Nature. 1995 Jan 12;373(6510):117-22 PMID: 7529365
  19. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.
    Nature. 1995 Jan 12;373(6510):123-6 PMID: 7816094
  20. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy.
    Science. 1995 Jan 27;267(5197):483-9 PMID: 7824947
  21. Intracellular susceptibility to ribozymes in a tethered substrate-ribozyme provirus model is not predicted by secondary structures of human immunodeficiency virus type 1 RNAs in vitro.
    Antisense Res Dev. 1994 Fall;4(3):217-21 PMID: 7849493
  22. The human immunodeficiency virus type 1 (HIV-1) CD4 receptor and its central role in promotion of HIV-1 infection.
    Microbiol Rev. 1995 Mar;59(1):63-93 PMID: 7708013
  23. RNA chaperones and the RNA folding problem.
    J Biol Chem. 1995 Sep 8;270(36):20871-4 PMID: 7545662
  24. Systemic gene therapy: biodistribution and long-term expression of a transgene in mice.
    Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9742-6 PMID: 7568209
  25. Nonviral gene therapy: the promise of genes as pharmaceutical products.
    Hum Gene Ther. 1995 Sep;6(9):1129-44 PMID: 8527471
  26. Initiation of polyribosome formation in poliovirus-infected HeLa cells.
    J Mol Biol. 1970 Feb 14;47(3):275-91 PMID: 4313849
  27. Viral interference by defective particles of vesicular stomatitis virus measured in individual cells.
    Virology. 1980 Jul 15;104(1):247-52 PMID: 6249028
  28. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.
    J Virol. 1986 Aug;59(2):284-91 PMID: 3016298
  29. Defective interfering viruses and infections of animals.
    Curr Top Microbiol Immunol. 1986;128:55-84 PMID: 3533448
  30. The chemistry of self-splicing RNA and RNA enzymes.
    Science. 1987 Jun 19;236(4808):1532-9 PMID: 2438771
  31. Envelope glycoprotein of HIV induces interference and cytolysis resistance in CD4+ cells: mechanism for persistence in AIDS.
    Cell. 1988 May 6;53(3):483-96 PMID: 2966682
  32. Extensive variation of human immunodeficiency virus type-1 in vivo.
    Nature. 1988 Aug 4;334(6181):440-4 PMID: 3405290
  33. Simple RNA enzymes with new and highly specific endoribonuclease activities.
    Nature. 1988 Aug 18;334(6183):585-91 PMID: 2457170
  34. Gene therapy. Intracellular immunization.
    Nature. 1988 Sep 29;335(6189):395-6 PMID: 3166513
  35. Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function.
    Cell. 1989 Jul 14;58(1):205-14 PMID: 2752419
  36. Mutational analysis of HIV-1 Tat minimal domain peptides: identification of trans-dominant mutants that suppress HIV-LTR-driven gene expression.
    Cell. 1989 Jul 14;58(1):215-23 PMID: 2752420
  37. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations.
    Cell. 1989 Sep 8;58(5):901-10 PMID: 2550139
  38. HIV-1 Gag mutants can dominantly interfere with the replication of the wild-type virus.
    Cell. 1989 Oct 6;59(1):113-20 PMID: 2676192
  39. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons.
    N Engl J Med. 1989 Dec 14;321(24):1621-5 PMID: 2586564
  40. Plasma viremia in human immunodeficiency virus infection.
    N Engl J Med. 1989 Dec 14;321(24):1626-31 PMID: 2511447
  41. Ribozymes as potential anti-HIV-1 therapeutic agents.
    Science. 1990 Mar 9;247(4947):1222-5 PMID: 2107573
  42. Noninfectious human immunodeficiency virus type 1 mutants deficient in genomic RNA.
    J Virol. 1990 Jul;64(7):3207-11 PMID: 2191147
  43. A transdominant tat mutant that inhibits tat-induced gene expression from the human immunodeficiency virus long terminal repeat.
    Proc Natl Acad Sci U S A. 1990 Jul;87(13):5079-83 PMID: 2195547
  44. Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication.
    Cell. 1990 Nov 2;63(3):601-8 PMID: 2225067
  45. Functional characterization of a U5 ribozyme: intracellular suppression of human immunodeficiency virus type 1 expression.
    J Virol. 1992 Mar;66(3):1432-41 PMID: 1738200
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1996-10-01
Pages
11103-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38291
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com