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Published on: September 14, 2010
Lentivirus-associated MAPK/ERK2 phosphorylates EMD and regulates infectivity
Terence N Bukong1, William W Hall, Jean-Marc Jacqué
1University College Dublin, Centre for Research in Infectious Diseases, Belfield, Dublin 4, Ireland.
The Journal of General Virology
|May 14, 2010
Summary
Virion-associated mitogen-activated protein kinase (MAPK) phosphorylates emerin (EMD) in target cells, facilitating lentiviral DNA integration. Inhibiting MAPK reduces viral integration, highlighting MAPK
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Lentivirus infection involves synthesizing viral DNA within a pre-integration complex (PIC).
- Nuclear import of PICs in non-dividing cells requires the nuclear lamina protein emerin (EMD).
Purpose of the Study:
- To investigate the role of emerin (EMD) phosphorylation in lentiviral infection.
- To determine the involvement of mitogen-activated protein kinase (MAPK) in EMD phosphorylation and viral integration.
Main Methods:
- Monitoring EMD phosphorylation post-infection in primary non-dividing cells.
- Utilizing MAPK kinase inhibitors to assess effects on EMD phosphorylation and viral DNA integration.
- Employing kinase-inactive and constitutively active MEK1 mutants in virus-producer cells.
Main Results:
- EMD phosphorylation occurs early after lentivirus infection and is dependent on virion-associated MAPK.
- MAPK inhibition significantly reduces EMD phosphorylation and proviral DNA integration.
- Impaired EMD phosphorylation and viral integration were observed when using a kinase-inactive MEK1 mutant.
Conclusions:
- Virion-associated MAPK facilitates lentiviral cDNA integration by phosphorylating target-cell EMD.
- MAPK plays a crucial role in post-nuclear translocation steps of lentiviral infection.
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