Linked Life Data

18279037

Source:http://linkedlifedata.com/resource/pubmed/id/18279037

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-3-25
pubmed:abstractText
Species-specific innate resistance against viral infections offers novel avenues for antiviral therapeutics. The retroviral restriction factor TRIM5alpha (tripartite motif 5alpha protein) has been shown to potently restrict human immunodeficiency virus (HIV)-1 infection in otherwise susceptible cell lines and CD34(+) cell-derived macrophages. A 13-amino acid patch in the C-terminal B30.2 (SPRY) domain of rhesus macaque TRIM5alpha has been shown to be involved in HIV-1 capsid recognition and is critical for viral inhibition. A chimeric human-rhesus TRIM5alpha (TRIM5alpha-HRH) was generated by replacing an 11-amino acid patch in the human isoform with the rhesus 13-amino acid patch. Here we show that lentiviral vector expression of this human-rhesus chimera in HIV-1-permissive MAGI-CXCR4 cells conferred resistance as well as a selective survival advantage on HIV-1 challenge. To apply these findings in a stem cell gene therapy setting, TRIM5alpha-HRH was expressed in CD34(+) cell-derived macrophages in vitro and in SCID-hu mouse-derived thymocytes in vivo. On viral challenge, transgenic macrophages and thymocytes were highly resistant to HIV-1 compared with control cells. Normal development of TRIM5alpha-HRH-expressing macrophages and in vivo-derived T cells was also observed by phenotypic flow cytometric analysis. These results demonstrate the efficacy of TRIM5alpha-HRH in a stem cell setting and its further advancement for use in gene therapy applications.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
217-28
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Human immunodeficiency virus type 1 restriction by human-rhesus chimeric tripartite motif 5alpha (TRIM 5alpha) in CD34(+) cell-derived macrophages in vitro and in T cells in vivo in severe combined immunodeficient (SCID-hu) mice transplanted with human fetal tissue.
pubmed:affiliation
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural