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N-terminally truncated POM121C inhibits HIV-1 replication
Hideki Saito1, Hiroaki Takeuchi1, Takao Masuda2
1Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Plos One
|September 6, 2017
Summary
A truncated nuclear pore protein, POM121C, blocks HIV-1 infection by interfering with viral DNA integration. This inhibition is linked to its interaction with importin-β (KPNB1), highlighting KPNB1
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Host cell factors regulate early human immunodeficiency virus type 1 (HIV-1) infection stages, including viral cDNA synthesis and capsid (CA) core orientation.
- Mechanisms of viral DNA import through the nuclear pore and integration into host DNA remain incompletely understood.
Purpose of the Study:
- To investigate the role of nuclear pore complex components in HIV-1 nuclear import and integration.
- To elucidate the mechanism by which N-terminally truncated POM121C inhibits HIV-1 infection.
Main Methods:
- Expression of N-terminally truncated POM121C in host cells.
- Analysis of HIV-1 infection stages, including cDNA synthesis, 2-LTR circle formation, and proviral DNA integration.
- Studies using HIV-1/murine leukemia virus (MLV) chimeric viruses to identify viral determinants of inhibition.
- Investigation of the interaction between truncated POM121C and importin-β (KPNB1) using mutational analysis.
Main Results:
- N-terminally truncated POM121C inhibits HIV-1 infection by reducing 2-LTR circle formation and proviral DNA integration.
- This truncated protein localizes to the cytoplasm, does not bind HIV-1 CA, and does not affect viral cDNA synthesis.
- The HIV-1 Gag protein is a determinant of inhibition by truncated POM121C.
- Inhibition by truncated POM121C is dependent on its binding to importin-β (KPNB1).
Conclusions:
- N-terminally truncated POM121C inhibits HIV-1 replication post-reverse transcription and pre-integration.
- The interaction between truncated POM121C and importin-β (KPNB1) is crucial for this inhibitory effect.
- Importin-β (KPNB1) plays a significant role in HIV-1 replication.