Linked Life Data

1714662

Source:http://linkedlifedata.com/resource/pubmed/id/1714662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-9-18
pubmed:abstractText
The genomes of HIV and SIV are complex and contain several accessory genes which modulate viral replication and pathogenicity. One of these genes, vpx, is unique to the HIV-2/SIV group of viruses and encodes a virion-associated protein of unknown function. To examine the function of vpx, we constructed a vpx-deficient HIV-2 proviral clone and characterized its in vitro biological properties. Following transfection into immortalized T-cell lines, vpx-mutant HIV-2 was fully replication competent and exhibited growth kinetics and cytopathic properties equivalent to wild-type HIV-2. In addition, vpx-deficient virions were indistinguishable from wild-type HIV-2 in ultrastructure, composition of major structural proteins, and reverse transcriptase activity. In PHA-stimulated normal peripheral blood mononuclear cells (PBMCs), however, vpx-deficient virus replicated at substantially lower titers and required a 100- to 1000-fold higher inoculum to establish a productive infection. This defect was localized to early events in the viral life cycle since vpx-deficient virus exhibited a 5- to 10-fold reduction in initial (single cycle) viral DNA synthesis following acute infection of primary PBMCs. Paradoxically, in long-term (9-23 months) cultures of immortalized T-cells (SupT1) continuous high level replication of vpx-deficient, but not wild-type, virus was observed, indicating less efficient viral spread and cell killing and a more attenuated phenotype of vpx-deficient HIV-2. Taken together, these results demonstrate that vpx is required for the production of fully infectious and cytopathic HIV-2 virions and that it functions early in the viral life cycle by facilitating viral entry and/or reverse transcription. The pronounced replicative defect of vpx-deficient HIV-2 in primary PBMCs but not in short-term cultures of immortalized T-cell lines emphasizes the need to characterize the properties of nonessential HIV accessory gene products in natural target cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:volume
184
pubmed:geneSymbol
vpx
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
197-209
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:1714662-Amino Acid Sequence, pubmed-meshheading:1714662-Base Sequence, pubmed-meshheading:1714662-Blotting, Southern, pubmed-meshheading:1714662-Cell Line, pubmed-meshheading:1714662-Cell Transformation, Viral, pubmed-meshheading:1714662-DNA, Viral, pubmed-meshheading:1714662-Genes, Viral, pubmed-meshheading:1714662-HIV Long Terminal Repeat, pubmed-meshheading:1714662-HIV-2, pubmed-meshheading:1714662-Humans, pubmed-meshheading:1714662-Kinetics, pubmed-meshheading:1714662-Molecular Sequence Data, pubmed-meshheading:1714662-Oligonucleotide Probes, pubmed-meshheading:1714662-Polymerase Chain Reaction, pubmed-meshheading:1714662-RNA-Directed DNA Polymerase, pubmed-meshheading:1714662-Restriction Mapping, pubmed-meshheading:1714662-Retroviridae Proteins, pubmed-meshheading:1714662-T-Lymphocytes, pubmed-meshheading:1714662-Transfection, pubmed-meshheading:1714662-Viral Regulatory and Accessory Proteins, pubmed-meshheading:1714662-Virion, pubmed-meshheading:1714662-Virus Replication
pubmed:year
1991
pubmed:articleTitle
Human immunodeficiency virus type 2 vpx protein augments viral infectivity.
pubmed:affiliation
Department of Medicine, University of Alabama, Birmingham 35294.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.