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Published on: January 16, 2017
Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies
Michael J Wichroski1, G Brett Robb, Tariq M Rana
1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Abstract:
APOBEC3G is an antiviral host factor capable of inhibiting the replication of both exogenous and endogenous retroviruses as well as hepatitis B, a DNA virus that replicates through an RNA intermediate. To gain insight into the mechanism whereby APOBEC3G restricts retroviral replication, we investigated the subcellular localization of the protein. Herein, we report that APOBEC3G localizes to mRNA processing (P) bodies, cytoplasmic compartments involved in the degradation and storage of nontranslating mRNAs. Biochemical analysis revealed that APOBEC3G localizes to a ribonucleoprotein complex with other P-body proteins which have established roles in cap-dependent translation (eIF4E and eIF4E-T), translation suppression (RCK/p54), RNA interference-mediated post-transcriptional gene silencing (AGO2), and decapping of mRNA (DCP2). Similar analysis with other APOBEC3 family members revealed a potential link between the localization of APOBEC3G and APOBEC3F to a common ribonucleoprotein complex and P-bodies with potent anti-HIV-1 activity. In addition, we present evidence suggesting that an important role for HIV-1 Vif, which subverts both APOBEC3G and APOBEC3F antiviral function by inducing their degradation, could be to selectively remove these proteins from and/or restrict their localization to P-bodies. Taken together, the results of this study reveal a novel link between innate immunity against retroviruses and P-bodies suggesting that APOBEC3G and APOBEC3F could function in the context of P-bodies to restrict HIV-1 replication.
Insights
The antiviral protein APOBEC3G localizes to P-bodies, crucial for mRNA regulation. This finding links innate immunity and P-bodies, suggesting APOBEC3G and APOBEC3F restrict HIV-1 replication within these compartments.
Area of Science:
- * Molecular Biology
- * Virology
- * Cellular Biology
Background:
- * APOBEC3G is a host factor that inhibits retroviral and hepatitis B virus replication.
- * Understanding APOBEC3G's mechanism requires investigating its subcellular localization.
- * P-bodies are cytoplasmic sites involved in mRNA regulation.
Purpose of the Study:
- * To determine the subcellular localization of APOBEC3G.
- * To elucidate the mechanism by which APOBEC3G restricts retroviral replication.
- * To explore the role of P-bodies in APOBEC3G's antiviral activity.
Main Methods:
- * Biochemical analysis of APOBEC3G localization.
- * Investigation of APOBEC3G's association with other P-body proteins.
- * Comparative analysis of APOBEC3 family members' localization.
Main Results:
- * APOBEC3G localizes to mRNA processing (P) bodies.
- * APOBEC3G forms ribonucleoprotein complexes with key P-body proteins involved in translation and gene silencing.
- * APOBEC3G and APOBEC3F localize to a common complex in P-bodies, correlating with anti-HIV-1 activity.
- * HIV-1 Vif may restrict APOBEC3G/APOBEC3F localization to P-bodies.
Conclusions:
- * APOBEC3G and APOBEC3F function within P-bodies to restrict HIV-1 replication.
- * A novel link exists between innate antiviral immunity and P-body function.
- * P-body localization is critical for the antiviral activity of APOBEC3G and APOBEC3F against retroviruses.
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