Structural Insights into APOBEC3-Mediated Lentiviral Restriction
Mammals have developed clever adaptive and innate immune defense mechanisms to protect against invading bacterial and viral pathogens. Human innate immunity is continuously evolving to expand the repertoire of restriction factors and one such family of intrinsic restriction factors is the APOBEC3 (A...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/6/587 |
| _version_ | 1797566885473026048 |
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| author | Krista A. Delviks-Frankenberry Belete A. Desimmie Vinay K. Pathak |
| author_facet | Krista A. Delviks-Frankenberry Belete A. Desimmie Vinay K. Pathak |
| author_sort | Krista A. Delviks-Frankenberry |
| collection | DOAJ |
| description | Mammals have developed clever adaptive and innate immune defense mechanisms to protect against invading bacterial and viral pathogens. Human innate immunity is continuously evolving to expand the repertoire of restriction factors and one such family of intrinsic restriction factors is the APOBEC3 (A3) family of cytidine deaminases. The coordinated expression of seven members of the A3 family of cytidine deaminases provides intrinsic immunity against numerous foreign infectious agents and protects the host from exogenous retroviruses and endogenous retroelements. Four members of the A3 proteins—A3G, A3F, A3H, and A3D—restrict HIV-1 in the absence of virion infectivity factor (Vif); their incorporation into progeny virions is a prerequisite for cytidine deaminase-dependent and -independent activities that inhibit viral replication in the host target cell. HIV-1 encodes Vif, an accessory protein that antagonizes A3 proteins by targeting them for polyubiquitination and subsequent proteasomal degradation in the virus producing cells. In this review, we summarize our current understanding of the role of human A3 proteins as barriers against HIV-1 infection, how Vif overcomes their antiviral activity, and highlight recent structural and functional insights into A3-mediated restriction of lentiviruses. |
| first_indexed | 2024-03-10T19:33:45Z |
| format | Article |
| id | doaj.art-710a8f87787a467888f845029a01ee67 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T19:33:45Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-710a8f87787a467888f845029a01ee672023-11-20T01:55:55ZengMDPI AGViruses1999-49152020-05-0112658710.3390/v12060587Structural Insights into APOBEC3-Mediated Lentiviral RestrictionKrista A. Delviks-Frankenberry0Belete A. Desimmie1Vinay K. Pathak2Viral Mutation Section, HIV Dynamics and Replication Program, National Cancer Institute at Frederick, Frederick, MD 21702, USAViral Mutation Section, HIV Dynamics and Replication Program, National Cancer Institute at Frederick, Frederick, MD 21702, USAViral Mutation Section, HIV Dynamics and Replication Program, National Cancer Institute at Frederick, Frederick, MD 21702, USAMammals have developed clever adaptive and innate immune defense mechanisms to protect against invading bacterial and viral pathogens. Human innate immunity is continuously evolving to expand the repertoire of restriction factors and one such family of intrinsic restriction factors is the APOBEC3 (A3) family of cytidine deaminases. The coordinated expression of seven members of the A3 family of cytidine deaminases provides intrinsic immunity against numerous foreign infectious agents and protects the host from exogenous retroviruses and endogenous retroelements. Four members of the A3 proteins—A3G, A3F, A3H, and A3D—restrict HIV-1 in the absence of virion infectivity factor (Vif); their incorporation into progeny virions is a prerequisite for cytidine deaminase-dependent and -independent activities that inhibit viral replication in the host target cell. HIV-1 encodes Vif, an accessory protein that antagonizes A3 proteins by targeting them for polyubiquitination and subsequent proteasomal degradation in the virus producing cells. In this review, we summarize our current understanding of the role of human A3 proteins as barriers against HIV-1 infection, how Vif overcomes their antiviral activity, and highlight recent structural and functional insights into A3-mediated restriction of lentiviruses.https://www.mdpi.com/1999-4915/12/6/587APOBEC3Gcytidine deaminationrestriction factorVifsubstrate selectionhypermutation |
| spellingShingle | Krista A. Delviks-Frankenberry Belete A. Desimmie Vinay K. Pathak Structural Insights into APOBEC3-Mediated Lentiviral Restriction Viruses APOBEC3G cytidine deamination restriction factor Vif substrate selection hypermutation |
| title | Structural Insights into APOBEC3-Mediated Lentiviral Restriction |
| title_full | Structural Insights into APOBEC3-Mediated Lentiviral Restriction |
| title_fullStr | Structural Insights into APOBEC3-Mediated Lentiviral Restriction |
| title_full_unstemmed | Structural Insights into APOBEC3-Mediated Lentiviral Restriction |
| title_short | Structural Insights into APOBEC3-Mediated Lentiviral Restriction |
| title_sort | structural insights into apobec3 mediated lentiviral restriction |
| topic | APOBEC3G cytidine deamination restriction factor Vif substrate selection hypermutation |
| url | https://www.mdpi.com/1999-4915/12/6/587 |
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