Linked Life Data

12551992

Source:http://linkedlifedata.com/resource/pubmed/id/12551992

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-1-28
pubmed:abstractText
Human immunodeficiency virus (HIV) gp120 induces multiple cellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3-kinase) pathway. The role of the PI3-kinase pathway in HIV-1 replication is not understood. Here we examined whether HIV-1 gp120 upregulates the PI3-kinase pathway and whether PI3-kinase activity plays a role in virus replication in primary human CD4(+) T cells and macrophages. Soluble and virion-associated HIV-1 gp120 induced calcium mobilization and phosphorylation of the PI3-kinase downstream effectors PKB/Akt and p70 S6 kinase. gp120-induced PI3-kinase activity and calcium mobilization were inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that the signaling is mediated through the chemokine receptor. The PI3-kinase inhibitor LY294002 inhibited infection of CD4(+) T cells and macrophages with X4 and R5 HIV-1-pseudotyped viruses at concentrations that did not induce cell toxicity or downregulate HIV-1 coreceptor expression. When gp120-induced signaling was bypassed with the vesicular stomatitis virus G envelope protein, infection was still sensitive to PI3-kinase inhibition, suggesting that basal PI3-kinase activity is required for infection. LY294002 inhibited HIV-1 infection when added after viral entry and did not affect formation of the HIV-1 reverse transcriptase products R/U5 and long terminal repeat/Gag in the presence of the inhibitor. However, when the inhibitor was added after viral integration had occurred, no inhibition of HIV infection was observed. Our studies show that inhibition of the PI3-kinase signaling pathway suppresses virus infection post-viral entry and post-reverse transcription but prior to HIV gene expression. This type of host-virus interaction has implications for anti-HIV therapeutics that target cellular signaling machinery.
pubmed:grant
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-538X
pubmed:author
pubmed:issnType
Print
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2539-49
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Phosphatidylinositol 3-kinase regulates human immunodeficiency virus type 1 replication following viral entry in primary CD4+ T lymphocytes and macrophages.
pubmed:affiliation
Division of Infectious Diseases, Mt. Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.