Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-2-25
pubmed:abstractText
Retroviruses including HIV-1 integrates a DNA copy of their RNA genome into cellular DNA of the infected cell. This reaction, essential and unique to replication of retroviruses, is mediated by the viral enzyme, integrase (IN). We constructed a recombinant gene encoding a single-chain, antigen-binding peptide (scAb2-19), which interacted with a carboxyl terminal part of HIV-1 IN. HeLa CD4 cells expressing scAb2-19 localized in either cytoplasmic or nuclear compartment were resistant to HIV-1 infection at an multiplicity of infection (MOI) of 0.25 or 0.063, but the resistance was overcome when MOI was increased to 1. To determine whether this resistance was due to inhibition of the early events, transduction experiments were performed with a replication-incompetent HIV-1 vector carrying bacterial lacZ driven by an internal Tat-independent cytomegalovirus immediate early promoter. Both cytoplasmic and nuclear expressions of scAb2-19 resulted in decrease in the transduction efficiency on HeLa CD4 cells. This implies that an early step of replication--before or during integration--was affected by the scAb2-19. Furthermore, cytoplasmic expression of scAb2-19 did not affect the viral amount released from the cells transfected with HIV-1 infectious clone DNA (pLAI). However, infectivity relative to reverse transcriptase activity was lower for virions released from the 293T cells cotransfected with pLAI and the cytoplasmic scAb2-19 expression plasmid than for those released from the 293T cells transfected with pLAI alone. This implies that scAb2-19 reduced infectivity of released virions by interfering a late step of the viral replication. The single-chain, antigen-binding peptide molecule may prove useful not only for studies of the functions of IN and its role in the viral life cycle but also for developing a gene therapy strategy against AIDS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1077-9450
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
105-14
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10048896-Amino Acid Sequence, pubmed-meshheading:10048896-Antibodies, Monoclonal, pubmed-meshheading:10048896-Base Sequence, pubmed-meshheading:10048896-Cell Line, pubmed-meshheading:10048896-Cell Nucleus, pubmed-meshheading:10048896-Cloning, Molecular, pubmed-meshheading:10048896-Cytoplasm, pubmed-meshheading:10048896-DNA Primers, pubmed-meshheading:10048896-Genetic Vectors, pubmed-meshheading:10048896-HIV Antibodies, pubmed-meshheading:10048896-HIV Integrase, pubmed-meshheading:10048896-HIV Integrase Inhibitors, pubmed-meshheading:10048896-HIV-1, pubmed-meshheading:10048896-HeLa Cells, pubmed-meshheading:10048896-Humans, pubmed-meshheading:10048896-Molecular Sequence Data, pubmed-meshheading:10048896-Transduction, Genetic, pubmed-meshheading:10048896-Virus Integration, pubmed-meshheading:10048896-Virus Replication
pubmed:year
1999
pubmed:articleTitle
Inhibition of replication of HIV-1 at both early and late stages of the viral life cycle by single-chain antibody against viral integrase.
pubmed:affiliation
Division of Molecular Genetics, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan. yochan@nih.go.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't