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Expression of HIV-1 nef decreases basal phosphatidyl-inositol 3-kinase activity
1Groupe de développement cellulaire et unité d'immunologie virale, Institut Pasteur, Paris, France.
Abstract:
CEM lymphoid cells expressing high levels of HIV-1 nef protein displayed a significant decrease in basal phosphatidyl-inositol 3-kinase (P13-kinase) activity associated with immunoprecipitates with anti-p85 regulatory subunit. In contrast, chronically infected U937 monocytic cells displayed a significant increase in basal P13-kinase activity in cells infected with HIV-1 nef compared to those infected with isogenic HIV-1 nef+. These findings suggest that HIV-1-nef expression is accompanied by a decrease in basal intracellular phosphatidyl-inositol 3-kinase activity and suggest that P13-kinase could be important for HIV-1 replication. Moreover, wortmannin, a potent in-vitro phosphatidyl-inositol 3-kinase inhibitor, can inhibit HIV-1 replication in U937 chronically infected cells. Together these results suggest a correlation between P13-kinase activity and HIV-1 replication.
Insights
HIV-1 nef protein impacts phosphatidyl-inositol 3-kinase (PI3K) activity, affecting viral replication. Inhibition of PI3K with wortmannin suppressed HIV-1 replication, suggesting PI3K
Area of Science:
- Molecular Virology
- Cellular Biology
- Immunology
Background:
- The HIV-1 nef protein is a key virulence factor influencing viral replication and pathogenesis.
- Phosphatidyl-inositol 3-kinase (PI3K) signaling pathways are crucial for various cellular processes, including immune cell function and viral infections.
Purpose of the Study:
- To investigate the role of HIV-1 nef protein expression on intracellular phosphatidyl-inositol 3-kinase (PI3K) activity.
- To determine the correlation between PI3K activity and HIV-1 replication.
Main Methods:
- Measuring basal PI3K activity in CEM lymphoid cells and chronically infected U937 monocytic cells expressing HIV-1 nef.
- Utilizing immunoprecipitation with anti-p85 regulatory subunit of PI3K.
- Assessing the effect of wortmannin, a PI3K inhibitor, on HIV-1 replication in infected cells.
Main Results:
- High-level HIV-1 nef expression in CEM cells correlated with decreased basal PI3K activity.
- Chronically infected U937 cells expressing HIV-1 nef showed increased basal PI3K activity compared to controls.
- Wortmannin significantly inhibited HIV-1 replication in U937 cells.
Conclusions:
- HIV-1 nef expression modulates intracellular PI3K activity, with differing effects in lymphoid versus monocytic cells.
- PI3K activity appears to play a significant role in HIV-1 replication.
- Targeting PI3K may represent a potential therapeutic strategy against HIV-1.