Home LiteratureArticle Details
该文献已被撤稿(Retracted Publication),引用前请核实。
PMID: 8197188 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retracted Publication

Potent inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody.

Duan L, Bagasra O, Laughlin MA, Oakes JW, Pomerantz RJ

Abstract

Human immunodeficiency virus type 1 (HIV-1) has a complex life cycle, which has made it a difficult target for conventional therapeutic modalities. A single-chain antibody moiety, directed against the HIV-1 regulatory protein Rev, which rescues unspliced viral RNA from the nucleus of infected cells, has now been developed. This anti-Rev single-chain construct (SFv) consists of both light and heavy chain variable regions of anti-Rev monoclonal antibody, which, when expressed intracellularly within human cells, potently inhibits HIV-1 replication. This intracellular SFv molecule is demonstrated to specifically antagonize Rev function. Thus, intracellular SFv expression, against a retroviral regulatory protein, may be useful as a gene therapeutic approach to combat HIV-1 infections.

MeSH Terms
Amino Acid Sequence Animals Antiviral Agents Blotting, Northern Fluorescent Antibody Technique Gene Products, rev/immunology HIV Antibodies/genetics,immunology HIV-1/immunology HeLa Cells Humans Mice Molecular Sequence Data Transfection Virus Replication rev Gene Products, Human Immunodeficiency Virus
Chemicals
Antiviral Agents Gene Products, rev HIV Antibodies rev Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Duan L
Dorrance H. Hamilton Laboratories, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Bagasra O
Laughlin M A
Oakes J W
Pomerantz R J
References (19)
19 references, click to expand
  1. Immunodeficiency virus rev trans-activator modulates the expression of the viral regulatory genes.
    Nature. 1988 Sep 8;335(6186):181-3 PMID: 3412474
  2. Gene therapy. Intracellular immunization.
    Nature. 1988 Sep 29;335(6189):395-6 PMID: 3166513
  3. 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
  4. Specific inhibition of human immunodeficiency virus type 1 replication by antisense oligonucleotides: an in vitro model for treatment.
    Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11209-13 PMID: 1454800
  5. 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
  6. Expression and targeting of intracellular antibodies in mammalian cells.
    EMBO J. 1990 Jan;9(1):101-8 PMID: 2153072
  7. Identification of sequences important in the nucleolar localization of human immunodeficiency virus Rev: relevance of nucleolar localization to function.
    J Virol. 1990 Feb;64(2):881-5 PMID: 2404140
  8. Cells nonproductively infected with HIV-1 exhibit an aberrant pattern of viral RNA expression: a molecular model for latency.
    Cell. 1990 Jun 29;61(7):1271-6 PMID: 2364429
  9. Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication.
    Cell. 1990 Nov 2;63(3):601-8 PMID: 2225067
  10. Man-made antibodies.
    Nature. 1991 Jan 24;349(6307):293-9 PMID: 1987490
  11. Ras C-terminal processing enzymes--new drug targets?
    Cell. 1991 Apr 5;65(1):1-4 PMID: 2013090
  12. Specific complex of human immunodeficiency virus type 1 rev and nucleolar B23 proteins: dissociation by the Rev response element.
    Mol Cell Biol. 1991 May;11(5):2567-75 PMID: 2017166
  13. Detection of mutations associated with zidovudine resistance in human immunodeficiency virus by use of the polymerase chain reaction.
    J Infect Dis. 1991 Dec;164(6):1075-81 PMID: 1720152
  14. Selective killing of CD4+ cells harboring a human immunodeficiency virus-inducible suicide gene prevents viral spread in an infected cell population.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):182-6 PMID: 1346066
  15. Efficient replication of human immunodeficiency virus type 1 requires a threshold level of Rev: potential implications for latency.
    J Virol. 1992 Mar;66(3):1809-13 PMID: 1738210
  16. CD14 is involved in control of human immunodeficiency virus type 1 expression in latently infected cells by lipopolysaccharide.
    Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6285-9 PMID: 1378624
  17. 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
  18. Mechanism of action of regulatory proteins encoded by complex retroviruses.
    Microbiol Rev. 1992 Sep;56(3):375-94 PMID: 1406488
  19. Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10802-6 PMID: 1438280
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
1994-05-24
Pages
5075-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC43934
Subset
IM
Grants
NIAID NIH HHS · AI31836 · United States
Corrections
CommentIn
RetractionIn
CommentIn
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: [email protected]