A Single Amino Acid of APOBEC3G Controls Its Species-specific Interaction with Virion Infectivity Factor (Vif)

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Feb 24

PMID 14978281

Citations 191

Authors

Barbel Schrofelbauer

Darlene Chen

Nathaniel R Landau

Affiliations

Soon will be listed here.

Abstract

The virion infectivity factor (Vif) accessory protein of HIV-1 forms a complex with the cellular cytidine deaminase APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) to block its antiviral activity. The antiviral property of APOBEC3G is conserved in several mammalian species, but the ability of Vif to block this activity is species-specific. HIV-1 Vif blocks human APOBEC3G but does not block the mouse or African green monkey (AGM) enzyme. Conversely, SIV(AGM) Vif blocks the antiviral activity of AGM but not human APOBEC3G. We demonstrate that the species specificity is caused by a single amino acid difference in APOBEC3G. Replacement of Asp-128 in human APOBEC3G with the Lys-128 of AGM APOBEC3G caused the enzyme to switch its interaction, becoming sensitive to SIV(AGM) Vif and resistant to HIV-1 Vif. Conversely, the reciprocal Lys to Asp switch in AGM APOBEC3G reversed its specificity for Vif. The reversal of biological activity was accompanied by the corresponding switch in the species specificity with which the enzyme physically associated with Vif and was excluded from virions. The charge of the amino acid at position 128 was a critical determinant of species specificity. Based on the crystal structure of the distantly related Escherichia coli cytidine deaminase, we propose that this amino acid is positioned on a solvent-exposed loop of APOBEC3G on the same face of the protein as the catalytic site.

Citing Articles

The impact of digital economy on high-quality economic development: Research based on the consumption expansion.

Li X, Wu Q PLoS One. 2023; 18(12):e0292925.

PMID: 38100500 PMC: 10723678. DOI: 10.1371/journal.pone.0292925.

MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors.

Pawar P, Gokavi J, Wakhare S, Bagul R, Ghule U, Khan I Viruses. 2023; 15(11).

PMID: 38005883 PMC: 10675553. DOI: 10.3390/v15112206.

Potent dual block to HIV-1 infection using lentiviral vectors expressing fusion inhibitor peptide mC46- and Vif-resistant APOBEC3G.

Delviks-Frankenberry K, Ojha C, Hermann K, Hu W, Torbett B, Pathak V Mol Ther Nucleic Acids. 2023; 33:794-809.

PMID: 37662965 PMC: 10470399. DOI: 10.1016/j.omtn.2023.08.007.

Structural insights into RNA bridging between HIV-1 Vif and antiviral factor APOBEC3G.

Kouno T, Shibata S, Shigematsu M, Hyun J, Kim T, Matsuo H Nat Commun. 2023; 14(1):4037.

PMID: 37419875 PMC: 10328928. DOI: 10.1038/s41467-023-39796-5.

The structural basis for HIV-1 Vif antagonism of human APOBEC3G.

Li Y, Langley C, Azumaya C, Echeverria I, Chesarino N, Emerman M Nature. 2023; 615(7953):728-733.

PMID: 36754086 PMC: 10033410. DOI: 10.1038/s41586-023-05779-1.

References

Gaddis N, Chertova E, Sheehy A, Henderson L, Malim M . Comprehensive investigation of the molecular defect in vif-deficient human immunodeficiency virus type 1 virions. J Virol. 2003; 77(10):5810-20. PMC: 154025. DOI: 10.1128/jvi.77.10.5810-5820.2003. View

Lecossier D, Bouchonnet F, Clavel F, Hance A . Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science. 2003; 300(5622):1112. DOI: 10.1126/science.1083338. View

Harris R, Bishop K, Sheehy A, Craig H, Petersen-Mahrt S, Watt I . DNA deamination mediates innate immunity to retroviral infection. Cell. 2003; 113(6):803-9. DOI: 10.1016/s0092-8674(03)00423-9. View

Zhang H, Yang B, Pomerantz R, Zhang C, Arunachalam S, Gao L . The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature. 2003; 424(6944):94-8. PMC: 1350966. DOI: 10.1038/nature01707. View

Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D . Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature. 2003; 424(6944):99-103. DOI: 10.1038/nature01709. View

Mariani R, Chen D, Schrofelbauer B, Navarro F, Konig R, Bollman B . Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell. 2003; 114(1):21-31. DOI: 10.1016/s0092-8674(03)00515-4. View

Stopak K, de Noronha C, Yonemoto W, Greene W . HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol Cell. 2003; 12(3):591-601. DOI: 10.1016/s1097-2765(03)00353-8. View

Kao S, Khan M, Miyagi E, Plishka R, Buckler-White A, Strebel K . The human immunodeficiency virus type 1 Vif protein reduces intracellular expression and inhibits packaging of APOBEC3G (CEM15), a cellular inhibitor of virus infectivity. J Virol. 2003; 77(21):11398-407. PMC: 229358. DOI: 10.1128/jvi.77.21.11398-11407.2003. View

Sheehy A, Gaddis N, Malim M . The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med. 2003; 9(11):1404-7. DOI: 10.1038/nm945. View

10.

Marin M, Rose K, Kozak S, Kabat D . HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med. 2003; 9(11):1398-403. DOI: 10.1038/nm946. View

11.

Yu X, Yu Y, Liu B, Luo K, Kong W, Mao P . Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science. 2003; 302(5647):1056-60. DOI: 10.1126/science.1089591. View

12.

Strebel K, Daugherty D, Clouse K, Cohen D, Folks T, Martin M . The HIV 'A' (sor) gene product is essential for virus infectivity. Nature. 1987; 328(6132):728-30. DOI: 10.1038/328728a0. View

13.

Gabuzda D, Lawrence K, Langhoff E, Terwilliger E, Dorfman T, Haseltine W . Role of vif in replication of human immunodeficiency virus type 1 in CD4+ T lymphocytes. J Virol. 1992; 66(11):6489-95. PMC: 240141. DOI: 10.1128/JVI.66.11.6489-6495.1992. View

14.

von Schwedler U, Song J, Aiken C, Trono D . Vif is crucial for human immunodeficiency virus type 1 proviral DNA synthesis in infected cells. J Virol. 1993; 67(8):4945-55. PMC: 237882. DOI: 10.1128/JVI.67.8.4945-4955.1993. View

15.

Betts L, Xiang S, Short S, Wolfenden R, Carter Jr C . Cytidine deaminase. The 2.3 A crystal structure of an enzyme: transition-state analog complex. J Mol Biol. 1994; 235(2):635-56. DOI: 10.1006/jmbi.1994.1018. View

16.

Anant S, MacGinnitie A, Davidson N . apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme, is a novel RNA-binding protein. J Biol Chem. 1995; 270(24):14762-7. View

17.

Trono D . HIV accessory proteins: leading roles for the supporting cast. Cell. 1995; 82(2):189-92. DOI: 10.1016/0092-8674(95)90306-2. View

18.

Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M . Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996; 381(6584):661-6. DOI: 10.1038/381661a0. View

19.

Simon J, Miller D, Fouchier R, Soares M, Peden K, Malim M . The regulation of primate immunodeficiency virus infectivity by Vif is cell species restricted: a role for Vif in determining virus host range and cross-species transmission. EMBO J. 1998; 17(5):1259-67. PMC: 1170474. DOI: 10.1093/emboj/17.5.1259. View

20.

Emerman M, Malim M . HIV-1 regulatory/accessory genes: keys to unraveling viral and host cell biology. Science. 1998; 280(5371):1880-4. DOI: 10.1126/science.280.5371.1880. View