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Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics

Published online by Cambridge University Press:  22 January 2010

John S. Albin  and
Reuben S. Harris
John S. Albin
Affiliation:
Department of Biochemistry, Molecular Biology & Biophysics, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Reuben S. Harris*
Affiliation:
Department of Biochemistry, Molecular Biology & Biophysics, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
*
*Corresponding author: Reuben Harris, Department of Biochemistry, Molecular Biology & Biophysics, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, 6-155 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA. E-mail: [email protected]
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Abstract

Restriction factors are natural cellular proteins that defend individual cells from viral infection. These factors include the APOBEC3 family of DNA cytidine deaminases, which restrict the infectivity of HIV-1 by hypermutating viral cDNA and inhibiting reverse transcription and integration. HIV-1 thwarts this restriction activity through its accessory protein virion infectivity factor (Vif), which uses multiple mechanisms to prevent APOBEC3 proteins such as APOBEC3G and APOBEC3F from entering viral particles. Here, we review the basic biology of the interactions between human APOBEC3 proteins and HIV-1 Vif. We also summarise, for the first time, current clinical data on the in vivo effects of APOBEC3 proteins, and survey strategies and progress towards developing therapeutics aimed at the APOBEC3–Vif axis.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 12 , January 2010 , e4
Copyright
Copyright © Cambridge University Press 2010

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References

References

The Los Alamos National Laboratory HIV Sequence Database provides not only an excellent collection of HIV sequence information, but also a number of analysis tools (e.g. Hypermut, a program designed to detect and analyse hypermutated sequences) and HIV reference materials:

1Chiu, Y.L. and Greene, W.C. (2008) The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annual Review of Immunology 26, 317-353CrossRefGoogle ScholarPubMed
2Harris, R.S. and Liddament, M.T. (2004) Retroviral restriction by APOBEC proteins. Nature Reviews Immunology 4, 868-877CrossRefGoogle ScholarPubMed
3Malim, M.H. and Emerman, M. (2008) HIV-1 accessory proteins–ensuring viral survival in a hostile environment. Cell Host and Microbe 3, 388-398CrossRefGoogle Scholar
4Gramberg, T., Sunseri, N. and Landau, N.R. (2009) Accessories to the crime: recent advances in HIV accessory protein biology. Current HIV/AIDS Reports 6, 36-42CrossRefGoogle Scholar
5Garrett, E.D., Tiley, L.S. and Cullen, B.R. (1991) Rev activates expression of the human immunodeficiency virus type 1 vif and vpr gene products. Journal of Virology 65, 1653-1657CrossRefGoogle ScholarPubMed
6Schwartz, S., Felber, B.K. and Pavlakis, G.N. (1991) Expression of human immunodeficiency virus type 1 vif and vpr mRNAs is Rev-dependent and regulated by splicing. Virology 183, 677-686CrossRefGoogle ScholarPubMed
7Kan, N.C. et al. (1986) Identification of HTLV-III/LAV sor gene product and detection of antibodies in human sera. Science 231, 1553-1555CrossRefGoogle ScholarPubMed
8Lee, T.H. et al. (1986) A new HTLV-III/LAV protein encoded by a gene found in cytopathic retroviruses. Science 231, 1546-1549CrossRefGoogle ScholarPubMed
9Sodroski, J. et al. (1986) Replicative and cytopathic potential of HTLV-III/LAV with sor gene deletions. Science 231, 1549-1553CrossRefGoogle ScholarPubMed
10Desrosiers, R.C. et al. (1998) Identification of highly attenuated mutants of simian immunodeficiency virus. Journal of Virology 72, 1431-1437CrossRefGoogle ScholarPubMed
11Strebel, K. et al. (1987) The HIV 'A' (sor) gene product is essential for virus infectivity. Nature 328, 728-730CrossRefGoogle Scholar
12Gabuzda, D.H. et al. (1992) Role of Vif in replication of human immunodeficiency virus type 1 in CD4+ T lymphocytes. Journal of Virology 66, 6489-6495CrossRefGoogle ScholarPubMed
13Gabuzda, D.H. et al. (1994) Essential role of vif in establishing productive HIV-1 infection in peripheral blood T lymphocytes and monocyte/macrophages. Journal of Acquired Immune Deficiency Syndromes 7, 908-915Google Scholar
14Fisher, A.G. et al. (1987) The sor gene of HIV-1 is required for efficient virus transmission in vitro. Science 237, 888-893CrossRefGoogle ScholarPubMed
15Simon, J.H. and Malim, M.H. (1996) The human immunodeficiency virus type 1 Vif protein modulates the postpenetration stability of viral nucleoprotein complexes. Journal of Virology 70, 5297-5305CrossRefGoogle ScholarPubMed
16Courcoul, M. et al. (1995) Peripheral blood mononuclear cells produce normal amounts of defective Vif- human immunodeficiency virus type 1 particles which are restricted for the preretrotranscription steps. Journal of Virology 69, 2068-2074CrossRefGoogle ScholarPubMed
17Goncalves, J. et al. (1996) Role of Vif in human immunodeficiency virus type 1 reverse transcription. Journal of Virology 70, 8701-8709CrossRefGoogle ScholarPubMed
18Sova, P. and Volsky, D.J. (1993) Efficiency of viral DNA synthesis during infection of permissive and nonpermissive cells with vif-negative human immunodeficiency virus type 1. Journal of Virology 67, 6322-6326CrossRefGoogle ScholarPubMed
19Madani, N. and Kabat, D. (1998) An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein. Journal of Virology 72, 10251-10255CrossRefGoogle ScholarPubMed
20Simon, J.H. et al. (1998) Evidence for a newly discovered cellular anti-HIV-1 phenotype. Nature Medicine 4, 1397-1400CrossRefGoogle ScholarPubMed
21Sheehy, A.M. et al. (2002) Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418, 646-650CrossRefGoogle ScholarPubMed
22Haché, G. et al. (2008) Evolution of HIV-1 isolates that use a novel Vif-independent mechanism to resist restriction by human APOBEC3G. Current Biology 18, 819-824CrossRefGoogle ScholarPubMed
23Jarmuz, A. et al. (2002) An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22. Genomics 79, 285-296CrossRefGoogle Scholar
24Petersen-Mahrt, S.K., Harris, R.S. and Neuberger, M.S. (2002) AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 418, 99-103CrossRefGoogle ScholarPubMed
25Harris, R.S., Petersen-Mahrt, S.K. and Neuberger, M.S. (2002) RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Molecular Cell 10, 1247-1253CrossRefGoogle ScholarPubMed
26Harris, R.S. et al. (2003) DNA deamination mediates innate immunity to retroviral infection. Cell 113, 803-809CrossRefGoogle ScholarPubMed
27Mangeat, B. et al. (2003) Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424, 99-103CrossRefGoogle ScholarPubMed
28Zhang, H. et al. (2003) The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 424, 94-98CrossRefGoogle ScholarPubMed
29Lecossier, D. et al. (2003) Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science 300, 1112CrossRefGoogle ScholarPubMed
30Browne, E.P., Allers, C. and Landau, N.R. (2009) Restriction of HIV-1 by APOBEC3G is cytidine deaminase-dependent. Virology 387, 313-321CrossRefGoogle ScholarPubMed
31Holmes, R.K. et al. (2007) APOBEC3F can inhibit the accumulation of HIV-1 reverse transcription products in the absence of hypermutation. Comparisons with APOBEC3G. Journal of Biological Chemistry 282, 2587-2595CrossRefGoogle ScholarPubMed
32Miyagi, E. et al. (2007) Enzymatically active APOBEC3G is required for efficient inhibition of human immunodeficiency virus type 1. Journal of Virology 81, 13346-13353CrossRefGoogle ScholarPubMed
33Schumacher, A.J. et al. (2008) The DNA deaminase activity of human APOBEC3G is required for Ty1, MusD, and human immunodeficiency virus type 1 restriction. Journal of Virology 82, 2652-2660CrossRefGoogle ScholarPubMed
34Shindo, K. et al. (2003) The enzymatic activity of CEM15/Apobec-3G is essential for the regulation of the infectivity of HIV-1 virion but not a sole determinant of its antiviral activity. Journal of Biological Chemistry 278, 44412-44416CrossRefGoogle Scholar
35Newman, E.N. et al. (2005) Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity. Current Biology 15, 166-170CrossRefGoogle ScholarPubMed
36Bishop, K.N., Holmes, R.K. and Malim, M.H. (2006) Antiviral potency of APOBEC proteins does not correlate with cytidine deamination. Journal of Virology 80, 8450-8458CrossRefGoogle Scholar
37Bishop, K.N. et al. (2008) APOBEC3G inhibits elongation of HIV-1 reverse transcripts. PLoS Pathogens 4, e1000231CrossRefGoogle ScholarPubMed
38Iwatani, Y. et al. (2007) Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G. Nucleic Acids Research 35, 7096-7108CrossRefGoogle ScholarPubMed
39Guo, F. et al. (2006) Inhibition of formula-primed reverse transcription by human APOBEC3G during human immunodeficiency virus type 1 replication. Journal of Virology 80, 11710-11722CrossRefGoogle ScholarPubMed
40Yang, Y. et al. (2007) Inhibition of initiation of reverse transcription in HIV-1 by human APOBEC3F. Virology 365, 92-100CrossRefGoogle ScholarPubMed
41Li, X.Y. et al. (2007) APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. Journal of Biological Chemistry 282, 32065-32074CrossRefGoogle ScholarPubMed
42Luo, K. et al. (2007) Cytidine deaminases APOBEC3G and APOBEC3F interact with human immunodeficiency virus type 1 integrase and inhibit proviral DNA formation. Journal of Virology 81, 7238-7248CrossRefGoogle ScholarPubMed
43Mbisa, J.L. et al. (2007) HIV-1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration. Journal of Virology 81, 7099-7110CrossRefGoogle ScholarPubMed
44Schumacher, A.J., Nissley, D.V. and Harris, R.S. (2005) APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast. Proceedings of the National Academy of Sciences of the United States of America 102, 9854-9859CrossRefGoogle ScholarPubMed
45Turelli, P. et al. (2004) Inhibition of hepatitis B virus replication by APOBEC3G. Science 303, 1829CrossRefGoogle ScholarPubMed
46Bogerd, H.P. et al. (2006) Cellular inhibitors of long interspersed element 1 and Alu retrotransposition. Proceedings of the National Academy of Sciences of the United States of America 103, 8780-8785CrossRefGoogle ScholarPubMed
47Muckenfuss, H. et al. (2006) APOBEC3 proteins inhibit human LINE-1 retrotransposition. Journal of Biological Chemistry 281, 22161-22172CrossRefGoogle ScholarPubMed
48Stenglein, M.D. and Harris, R.S. (2006) APOBEC3B and APOBEC3F inhibit L1 retrotransposition by a DNA deamination-independent mechanism. Journal of Biological Chemistry 281, 16837-16841CrossRefGoogle ScholarPubMed
49Holmes, R.K., Malim, M.H. and Bishop, K.N. (2007) APOBEC-mediated viral restriction: not simply editing? Trends in Biochemical Sciences 32, 118-128CrossRefGoogle Scholar
50Bonvin, M. and Greeve, J. (2008) Hepatitis B: modern concepts in pathogenesis–APOBEC3 cytidine deaminases as effectors in innate immunity against the hepatitis B virus. Current Opinion in Infectious Diseases 21, 298-303CrossRefGoogle ScholarPubMed
51Harris, R.S. et al. (2003) DNA deamination: not just a trigger for antibody diversification but also a mechanism for defense against retroviruses. Nature Immunology 4, 641-643CrossRefGoogle Scholar
52Yang, B. et al. (2007) Virion-associated uracil DNA glycosylase-2 and apurinic/apyrimidinic endonuclease are involved in the degradation of APOBEC3G-edited nascent HIV-1 DNA. Journal of Biological Chemistry 282, 11667-11675CrossRefGoogle ScholarPubMed
53Chen, R. et al. (2004) Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages. Journal of Biological Chemistry 279, 28419-28425CrossRefGoogle ScholarPubMed
54Mansky, L.M. et al. (2000) The interaction of vpr with uracil DNA glycosylase modulates the human immunodeficiency virus type 1 In vivo mutation rate. Journal of Virology 74, 7039-7047CrossRefGoogle ScholarPubMed
55Priet, S. et al. (2005) HIV-1-associated uracil DNA glycosylase activity controls dUTP misincorporation in viral DNA and is essential to the HIV-1 life cycle. Molecular Cell 17, 479-490CrossRefGoogle Scholar
56Schröfelbauer, B. et al. (2005) Human immunodeficiency virus type 1 Vpr induces the degradation of the UNG and SMUG uracil-DNA glycosylases. Journal of Virology 79, 10978-10987CrossRefGoogle ScholarPubMed
57Kaiser, S.M. and Emerman, M. (2006) Uracil DNA glycosylase is dispensable for human immunodeficiency virus type 1 replication and does not contribute to the antiviral effects of the cytidine deaminase APOBEC3G. Journal of Virology 80, 875-882CrossRefGoogle ScholarPubMed
58Conticello, S.G., Harris, R.S. and Neuberger, M.S. (2003) The Vif protein of HIV triggers degradation of the human antiretroviral DNA deaminase APOBEC3G. Current Biology 13, 2009-2013CrossRefGoogle ScholarPubMed
59Marin, M. et al. (2003) HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nature Medicine 9, 1398-1403CrossRefGoogle ScholarPubMed
60Sheehy, A.M., Gaddis, N.C. and Malim, M.H. (2003) The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nature Medicine 9, 1404-1407CrossRefGoogle ScholarPubMed
61Stopak, K. et al. (2003) HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Molecular Cell 12, 591-601CrossRefGoogle ScholarPubMed
62Yu, X. et al. (2003) Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science 302, 1056-1060CrossRefGoogle ScholarPubMed
63Mehle, A. et al. (2004) Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway. Journal of Biological Chemistry 279, 7792-7798CrossRefGoogle ScholarPubMed
64Mehle, A. et al. (2004) Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation. Genes and Development 18, 2861-2866CrossRefGoogle ScholarPubMed
65Yu, Y. et al. (2004) Selective assembly of HIV-1 Vif-Cul5-ElonginB-ElonginC E3 ubiquitin ligase complex through a novel SOCS box and upstream cysteines. Genes and Development 18, 2867-2872CrossRefGoogle ScholarPubMed
66Kao, S. et al. (2003) The human immunodeficiency virus type 1 Vif protein reduces intracellular expression and inhibits packaging of APOBEC3G (CEM15), a cellular inhibitor of virus infectivity. Journal of Virology 77, 11398-11407CrossRefGoogle ScholarPubMed
67Mariani, R. et al. (2003) Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 114, 21-31CrossRefGoogle ScholarPubMed
68Santa-Marta, M. et al. (2005) HIV-1 Vif can directly inhibit apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G-mediated cytidine deamination by using a single amino acid interaction and without protein degradation. Journal of Biological Chemistry 280, 8765-8775CrossRefGoogle ScholarPubMed
69Conticello, S.G. et al. (2005) Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases. Molecular Biology and Evolution 22, 367-377CrossRefGoogle ScholarPubMed
70Wedekind, J.E. et al. (2003) Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business. Trends in Genetics 19, 207-216CrossRefGoogle ScholarPubMed
71Malim, M.H. (2009) APOBEC proteins and intrinsic resistance to HIV-1 infection. Philosophical Transactions of the Royal Society of London Series B Biological Sciences 364, 675-687CrossRefGoogle ScholarPubMed
72Li, Q. et al. (2009) Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection. Journal of Immunology 183, 1975-1982CrossRefGoogle ScholarPubMed
73OhAinle, M. et al. (2008) Antiretroelement activity of APOBEC3H was lost twice in recent human evolution. Cell Host and Microbe 4, 249-259CrossRefGoogle ScholarPubMed
74Harari, A. et al. (2009) Polymorphisms and splice variants influence the antiretroviral activity of human APOBEC3H. Journal of Virology 83, 295-303CrossRefGoogle ScholarPubMed
75Tan, L. et al. (2009) Sole copy of Z2-type human cytidine deaminase APOBEC3H has inhibitory activity against retrotransposons and HIV-1. FASEB Journal 23, 279-287CrossRefGoogle ScholarPubMed
76Yu, Q. et al. (2004) APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. Journal of Biological Chemistry 279, 53379-53386CrossRefGoogle ScholarPubMed
77Yu, Q. et al. (2004) Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nature Structural and Molecular Biology 11, 435-442CrossRefGoogle ScholarPubMed
78Bishop, K.N. et al. (2004) Cytidine deamination of retroviral DNA by diverse APOBEC proteins. Current Biology 14, 1392-1396CrossRefGoogle ScholarPubMed
79Liddament, M.T. et al. (2004) APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo. Current Biology 14, 1385-1391CrossRefGoogle ScholarPubMed
80Wiegand, H.L. et al. (2004) A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins. EMBO Journal 23, 2451-2458CrossRefGoogle ScholarPubMed
81Zheng, Y.H. et al. (2004) Human APOBEC3F is another host factor that blocks human immunodeficiency virus type 1 replication. Journal of Virology 78, 6073-6076CrossRefGoogle ScholarPubMed
82Watts, J.M. et al. (2009) Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460, 711-716CrossRefGoogle ScholarPubMed
83Janini, M. et al. (2001) Human immunodeficiency virus type 1 DNA sequences genetically damaged by hypermutation are often abundant in patient peripheral blood mononuclear cells and may be generated during near-simultaneous infection and activation of CD4(+) T cells. Journal of Virology 75, 7973-7986CrossRefGoogle ScholarPubMed
84Vartanian, J.P. et al. (1991) Selection, recombination, and G--A hypermutation of human immunodeficiency virus type 1 genomes. Journal of Virology 65, 1779-1788CrossRefGoogle ScholarPubMed
85Vartanian, J.P. et al. (1994) G--> A hypermutation of the human immunodeficiency virus type 1 genome: evidence for dCTP pool imbalance during reverse transcription. Proceedings of the National Academy of Sciences of the United States of America 91, 3092-3096CrossRefGoogle Scholar
86Pathak, V.K. and Temin, H.M. (1990) Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations. Proceedings of the National Academy of Sciences of the United States of America 87, 6019-6023CrossRefGoogle Scholar
87Kieffer, T.L. et al. (2005) G--> A hypermutation in protease and reverse transcriptase regions of human immunodeficiency virus type 1 residing in resting CD4+ T cells in vivo. Journal of Virology 79, 1975-1980CrossRefGoogle Scholar
88Pace, C. et al. (2006) Population level analysis of human immunodeficiency virus type 1 hypermutation and its relationship with APOBEC3G and vif genetic variation. Journal of Virology 80, 9259-9269CrossRefGoogle ScholarPubMed
89Piantadosi, A. et al. (2009) Analysis of the percentage of human immunodeficiency virus type 1 sequences that are hypermutated and markers of disease progression in a longitudinal cohort, including one individual with a partially defective Vif. Journal of Virology 83, 7805-7814CrossRefGoogle Scholar
90Land, A.M. et al. (2008) Human immunodeficiency virus (HIV) type 1 proviral hypermutation correlates with CD4 count in HIV-infected women from Kenya. Journal of Virology 82, 8172-8182CrossRefGoogle ScholarPubMed
91Gandhi, S.K. et al. (2008) Role of APOBEC3G/F-mediated hypermutation in the control of human immunodeficiency virus type 1 in elite suppressors. Journal of Virology 82, 3125-3130CrossRefGoogle ScholarPubMed
92Ulenga, N.K. et al. (2008) The level of APOBEC3G (hA3G)-related G-to-A mutations does not correlate with viral load in HIV type 1-infected individuals. AIDS Research and Human Retroviruses 24, 1285-1290CrossRefGoogle Scholar
93Kidd, J.M. et al. (2007) Population stratification of a common APOBEC gene deletion polymorphism. PLoS Genetics 3, e63CrossRefGoogle ScholarPubMed
94Mulder, L.C., Harari, A. and Simon, V. (2008) Cytidine deamination induced HIV-1 drug resistance. Proceedings of the National Academy of Sciences of the United States of America 105, 5501-5506CrossRefGoogle ScholarPubMed
95Berkhout, B. and de Ronde, A. (2004) APOBEC3G versus reverse transcriptase in the generation of HIV-1 drug-resistance mutations. AIDS 18, 1861-1863CrossRefGoogle ScholarPubMed
96Haché, G., Mansky, L.M. and Harris, R.S. (2006) Human APOBEC3 proteins, retrovirus restriction, and HIV drug resistance. AIDS Reviews 8, 148-157Google ScholarPubMed
97Pillai, S.K., Wong, J.K. and Barbour, J.D. (2008) Turning up the volume on mutational pressure: is more of a good thing always better? (A case study of HIV-1 Vif and APOBEC3). Retrovirology 5, 26CrossRefGoogle Scholar
98Jern, P. et al. (2009) Likely role of APOBEC3G-mediated G-to-A mutations in HIV-1 evolution and drug resistance. PLoS Pathogens 5, e1000367CrossRefGoogle ScholarPubMed
99Wood, N. et al. (2009) HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC. PLoS Pathogens 5, e1000414CrossRefGoogle ScholarPubMed
100Vázquez-Pérez, J.A. et al. (2009) APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression. Retrovirology 6, 23CrossRefGoogle ScholarPubMed
101Jin, X. et al. (2005) APOBEC3G/CEM15 (hA3G) mRNA levels associate inversely with human immunodeficiency virus viremia. Journal of Virology 79, 11513-11516CrossRefGoogle ScholarPubMed
102Cho, S.J. et al. (2006) APOBEC3F and APOBEC3G mRNA levels do not correlate with human immunodeficiency virus type 1 plasma viremia or CD4+ T-cell count. Journal of Virology 80, 2069-2072CrossRefGoogle ScholarPubMed
103Ulenga, N.K. et al. (2008) Relationship between human immunodeficiency type 1 infection and expression of human APOBEC3G and APOBEC3F. Journal of Infectious Diseases 198, 486-492CrossRefGoogle ScholarPubMed
104Biasin, M. et al. (2007) Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G: a possible role in the resistance to HIV of HIV-exposed seronegative individuals. Journal of Infectious Diseases 195, 960-964CrossRefGoogle ScholarPubMed
105Do, H. et al. (2005) Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French cohort. Journal of Infectious Diseases 191, 159-163CrossRefGoogle Scholar
106An, P. et al. (2004) APOBEC3G genetic variants and their influence on the progression to AIDS. Journal of Virology 78, 11070-11076CrossRefGoogle ScholarPubMed
107Valcke, H.S. et al. (2006) APOBEC3G genetic variants and their association with risk of HIV infection in highly exposed Caucasians. AIDS 20, 1984-1986CrossRefGoogle ScholarPubMed
108An, P. et al. (2009) APOBEC3B deletion and risk of HIV-1 acquisition. Journal of Infectious Diseases 200, 1054-1058CrossRefGoogle ScholarPubMed
109OhAinle, M. et al. (2006) Adaptive evolution and antiviral activity of the conserved mammalian cytidine deaminase APOBEC3H. Journal of Virology 80, 3853-3862CrossRefGoogle ScholarPubMed
110Sawyer, S.L., Emerman, M. and Malik, H.S. (2004) Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G. PLoS Biology 2, E275CrossRefGoogle ScholarPubMed
111Chiu, Y.L. et al. (2005) Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells. Nature 435, 108-114CrossRefGoogle ScholarPubMed
112Chen, K. et al. (2006) Alpha interferon potently enhances the anti-human immunodeficiency virus type 1 activity of APOBEC3G in resting primary CD4 T cells. Journal of Virology 80, 7645-7657CrossRefGoogle ScholarPubMed
113Santoni de Sio, F.R. and Trono, D. (2009) APOBEC3G-depleted resting CD4+ T cells remain refractory to HIV1 infection. PLoS One 4, e6571CrossRefGoogle ScholarPubMed
114Kamata, M., Nagaoka, Y. and Chen, I.S. (2009) Reassessing the role of APOBEC3G in human immunodeficiency virus type 1 infection of quiescent CD4+ T-cells. PLoS Pathogens 5, e1000342CrossRefGoogle ScholarPubMed
115Vetter, M.L. et al. (2009) Differences in APOBEC3G expression in CD4+ T helper lymphocyte subtypes modulate HIV-1 infectivity. PLoS Pathogens 5, e1000292CrossRefGoogle ScholarPubMed
116Koning, F.A. et al. (2009) Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets. Journal of Virology 83, 9474-9485CrossRefGoogle ScholarPubMed
117Peng, G. et al. (2007) Myeloid differentiation and susceptibility to HIV-1 are linked to APOBEC3 expression. Blood 110, 393-400CrossRefGoogle ScholarPubMed
118Pion, M. et al. (2006) APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection. Journal of Experimental Medicine 203, 2887-2893CrossRefGoogle ScholarPubMed
119Peng, G. et al. (2006) Induction of APOBEC3 family proteins, a defensive maneuver underlying interferon-induced anti-HIV-1 activity. Journal of Experimental Medicine 203, 41-46CrossRefGoogle ScholarPubMed
120Russell, R.A. and Pathak, V.K. (2007) Identification of two distinct human immunodeficiency virus type 1 Vif determinants critical for interactions with human APOBEC3G and APOBEC3F. Journal of Virology 81, 8201-8210CrossRefGoogle ScholarPubMed
121Simon, V. et al. (2005) Natural variation in Vif: differential impact on APOBEC3G/3F and a potential role in HIV-1 diversification. PLoS Pathogens 1, e6CrossRefGoogle Scholar
122Zhang, W. et al. (2008) Distinct determinants in HIV-1 Vif and human APOBEC3 proteins are required for the suppression of diverse host anti-viral proteins. PLoS One 3, e3963CrossRefGoogle ScholarPubMed
123He, Z. et al. (2008) Characterization of conserved motifs in HIV-1 Vif required for APOBEC3G and APOBEC3F interaction. Journal of Molecular Biology 381, 1000-1011CrossRefGoogle ScholarPubMed
124Tian, C. et al. (2006) Differential requirement for conserved tryptophans in human immunodeficiency virus type 1 Vif for the selective suppression of APOBEC3G and APOBEC3F. Journal of Virology 80, 3112-3115CrossRefGoogle ScholarPubMed
125Yamashita, T. et al. (2008) Identification of amino acid residues in HIV-1 Vif critical for binding and exclusion of APOBEC3G/F. Microbes and Infection 10, 1142-1149CrossRefGoogle ScholarPubMed
126Huthoff, H. et al. (2009) RNA-dependent oligomerization of APOBEC3G is required for restriction of HIV-1. PLoS Pathogens 5, e1000330CrossRefGoogle ScholarPubMed
127Huthoff, H. and Malim, M.H. (2007) Identification of amino acid residues in APOBEC3G required for regulation by human immunodeficiency virus type 1 Vif and Virion encapsidation. Journal of Virology 81, 3807-3815CrossRefGoogle ScholarPubMed
128Russell, R.A. et al. (2009) Distinct domains within APOBEC3G and APOBEC3F interact with separate regions of human immunodeficiency virus type 1 Vif. Journal of Virology 83, 1992-2003CrossRefGoogle ScholarPubMed
129Zhang, L. et al. (2008) Function analysis of sequences in human APOBEC3G involved in Vif-mediated degradation. Virology 370, 113-121CrossRefGoogle ScholarPubMed
130Pery, E. et al. (2009) Regulation of APOBEC3 proteins by a novel YXXL motif in human immunodeficiency virus type 1 Vif and simian immunodeficiency virus SIVagm Vif. Journal of Virology 83, 2374-2381CrossRefGoogle ScholarPubMed
131Chen, G. et al. (2009) A patch of positively charged amino acids surrounding the human immunodeficiency virus type 1 Vif SLVx4Yx9Y motif influences its interaction with APOBEC3G. Journal of Virology 83, 8674-8682CrossRefGoogle ScholarPubMed
132Dang, Y. et al. (2009) Identification of a novel WxSLVK motif in the N terminus of human immunodeficiency virus and simian immunodeficiency virus Vif that is critical for APOBEC3G and APOBEC3F neutralization. Journal of Virology 83, 8544-8552CrossRefGoogle Scholar
133Harjes, E. et al. (2009) An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model. Journal of Molecular Biology 389, 819-832CrossRefGoogle ScholarPubMed
134Nathans, R. et al. (2008) Small-molecule inhibition of HIV-1 Vif. Nature Biotechnology 26, 1187-1192CrossRefGoogle ScholarPubMed
135Chen, K.M. et al. (2008) Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G. Nature 452, 116-119CrossRefGoogle ScholarPubMed
136Holden, L.G. et al. (2008) Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications. Nature 456, 121-124CrossRefGoogle ScholarPubMed
137Furukawa, A. et al. (2009) Structure, interaction and real-time monitoring of the enzymatic reaction of wild-type APOBEC3G. EMBO Journal 28, 440-451CrossRefGoogle ScholarPubMed
138Prochnow, C. et al. (2007) The APOBEC-2 crystal structure and functional implications for the deaminase AID. Nature 445, 447-451CrossRefGoogle ScholarPubMed
139Bransteitter, R., Prochnow, C. and Chen, X.S. (2009) The current structural and functional understanding of APOBEC deaminases. Cellular and Molecular Life Sciences 66, 3137-3147CrossRefGoogle ScholarPubMed
140Mitsuyasu, R.T. et al. (2009) Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells. Nature Medicine 15, 285-292CrossRefGoogle ScholarPubMed
141Hutter, G. et al. (2009) Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. New England Journal of Medicine 360, 692-698CrossRefGoogle ScholarPubMed
142Rossi, J.J., June, C.H. and Kohn, D.B. (2007) Genetic therapies against HIV. Nature Biotechnology 25, 1444-1454CrossRefGoogle Scholar
143Bogerd, H.P. et al. (2004) A single amino acid difference in the host APOBEC3G protein controls the primate species specificity of HIV type 1 virion infectivity factor. Proceedings of the National Academy of Sciences of the United States of America 101, 3770-3774CrossRefGoogle ScholarPubMed
144Mangeat, B. et al. (2004) A single amino acid determinant governs the species-specific sensitivity of APOBEC3G to Vif action. Journal of Biological Chemistry 279, 14481-14483CrossRefGoogle ScholarPubMed
145Schröfelbauer, B., Chen, D. and Landau, N.R. (2004) A single amino acid of APOBEC3G controls its species-specific interaction with virion infectivity factor (Vif). Proceedings of the National Academy of Sciences of the United States of America 101, 3927-3932CrossRefGoogle ScholarPubMed
146Xu, H. et al. (2004) A single amino acid substitution in human APOBEC3G antiretroviral enzyme confers resistance to HIV-1 virion infectivity factor-induced depletion. Proceedings of the National Academy of Sciences of the United States of America 101, 5652-5657CrossRefGoogle ScholarPubMed
147Li, L. et al. (2008) APOBEC3G-UBA2 fusion as a potential strategy for stable expression of APOBEC3G and inhibition of HIV-1 replication. Retrovirology 5, 72CrossRefGoogle ScholarPubMed
148Yamanaka, S. et al. (1995) Apolipoprotein B mRNA-editing protein induces hepatocellular carcinoma and dysplasia in transgenic animals. Proceedings of the National Academy of Sciences of the United States of America 92, 8483-8487CrossRefGoogle ScholarPubMed
149Ao, Z. et al. (2008) Vpr14-88-Apobec3G fusion protein is efficiently incorporated into Vif-positive HIV-1 particles and inhibits viral infection. PLoS One 3, e1995CrossRefGoogle ScholarPubMed
150Aguiar, R.S. et al. (2008) Vpr.A3A chimera inhibits HIV replication. Journal of Biological Chemistry 283, 2518-2525CrossRefGoogle ScholarPubMed
151Green, L.A., Liu, Y. and He, J.J. (2009) Inhibition of HIV-1 infection and replication by enhancing viral incorporation of innate anti-HIV-1 protein A3G: a non-pathogenic Nef mutant-based anti-HIV strategy. Journal of Biological Chemistry 284, 13363-13372CrossRefGoogle ScholarPubMed
152Goila-Gaur, R. et al. (2007) Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity. Retrovirology 4, 61CrossRefGoogle Scholar
153Marin, M. et al. (2008) Human immunodeficiency virus type 1 Vif functionally interacts with diverse APOBEC3 cytidine deaminases and moves with them between cytoplasmic sites of mRNA metabolism. Journal of Virology 82, 987-998CrossRefGoogle ScholarPubMed
154Rose, K.M. et al. (2005) Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G. AIDS Research and Human Retroviruses 21, 611-619CrossRefGoogle ScholarPubMed
155Bogerd, H.P. et al. (2008) Equine infectious anemia virus resists the antiretroviral activity of equine APOBEC3 proteins through a packaging-independent mechanism. Journal of Virology 82, 11889-11901CrossRefGoogle ScholarPubMed
156Bogerd, H.P. et al. (2006) APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in human cells. Nucleic Acids Research 34, 89-95CrossRefGoogle ScholarPubMed
157Chen, H. et al. (2006) APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons. Current Biology 16, 480-485CrossRefGoogle ScholarPubMed
158Gooch, B.D. and Cullen, B.R. (2008) Functional domain organization of human APOBEC3G. Virology 379, 118-124CrossRefGoogle ScholarPubMed
159Kinomoto, M. et al. (2007) All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition. Nucleic Acids Research 35, 2955-2964CrossRefGoogle ScholarPubMed
160Bogerd, H.P. et al. (2007) The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active cytidine deaminase domains. Virology 364, 486-493CrossRefGoogle ScholarPubMed
161Doehle, B.P., Schafer, A. and Cullen, B.R. (2005) Human APOBEC3B is a potent inhibitor of HIV-1 infectivity and is resistant to HIV-1 Vif. Virology 339, 281-288CrossRefGoogle ScholarPubMed
162Hakata, Y. and Landau, N.R. (2006) Reversed functional organization of mouse and human APOBEC3 cytidine deaminase domains. Journal of Biological Chemistry 281, 36624-36631CrossRefGoogle ScholarPubMed
163Langlois, M.A. et al. (2005) Mutational comparison of the single-domained APOBEC3C and double-domained APOBEC3F/G anti-retroviral cytidine deaminases provides insight into their DNA target site specificities. Nucleic Acids Research 33, 1913-1923CrossRefGoogle ScholarPubMed
164Dang, Y. et al. (2008) Human cytidine deaminase APOBEC3H restricts HIV-1 replication. Journal of Biological Chemistry 283, 11606-11614CrossRefGoogle ScholarPubMed
165Dang, Y. et al. (2006) Identification of APOBEC3DE as another antiretroviral factor from the human APOBEC family. Journal of Virology 80, 10522-10533CrossRefGoogle ScholarPubMed
166Han, Y. et al. (2008) APOBEC3G and APOBEC3F require an endogenous cofactor to block HIV-1 replication. PLoS Pathogens 4, e1000095CrossRefGoogle ScholarPubMed
167Li, M.M., Wu, L.I. and Emerman, M. (2010) The range of human APOBEC3H sensitivity to lentiviral Vif proteins. Journal of Virology 84, 88-95CrossRefGoogle ScholarPubMed
168Stenglein, M.D. et al. (2010) APOBEC3 proteins mediate the clearance of foreign DNA from human cells. Nature Structural & Molecular Biology Jan 10; [Epub ahead of print]CrossRefGoogle ScholarPubMed
Chiu, Y.L. and Greene, W.C. (2008) The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annual Review of Immunology 26, 317-353CrossRefGoogle ScholarPubMed
Malim, M.H. and Emerman, M. (2008) HIV-1 accessory proteins–ensuring viral survival in a hostile environment. Cell Host and Microbe 3, 388-398CrossRefGoogle Scholar
Smith, J.L. et al. (2009) Multiple ways of targeting APOBEC3-virion infectivity factor interactions for anti-HIV-1 drug development. Trends in Pharmacological Sciences 30, 638-646CrossRefGoogle ScholarPubMed
Goila-Gaur, R. and Strebel, K. (2008) HIV-1 Vif, APOBEC, and intrinsic immunity. Retrovirology 5, 51CrossRefGoogle ScholarPubMed
Henriet, S. et al. (2009) Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC3G and APOBEC3F restriction factors. Microbiology and Molecular Biology Reviews 73, 211-232CrossRefGoogle ScholarPubMed
Malim, M.H. (2009) APOBEC proteins and intrinsic resistance to HIV-1 infection. Philosophical Transactions of the Royal Society of London Series B Biological Sciences 364, 675-687CrossRefGoogle ScholarPubMed
http://www.hiv.lanl.gov/content/sequence/HIV/mainpage.htmlGoogle Scholar
http://hivdb.stanford.edu/Google Scholar
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=rv.TOCGoogle Scholar
Chiu, Y.L. and Greene, W.C. (2008) The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annual Review of Immunology 26, 317-353CrossRefGoogle ScholarPubMed
Malim, M.H. and Emerman, M. (2008) HIV-1 accessory proteins–ensuring viral survival in a hostile environment. Cell Host and Microbe 3, 388-398CrossRefGoogle Scholar
Smith, J.L. et al. (2009) Multiple ways of targeting APOBEC3-virion infectivity factor interactions for anti-HIV-1 drug development. Trends in Pharmacological Sciences 30, 638-646CrossRefGoogle ScholarPubMed
Goila-Gaur, R. and Strebel, K. (2008) HIV-1 Vif, APOBEC, and intrinsic immunity. Retrovirology 5, 51CrossRefGoogle ScholarPubMed
Henriet, S. et al. (2009) Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC3G and APOBEC3F restriction factors. Microbiology and Molecular Biology Reviews 73, 211-232CrossRefGoogle ScholarPubMed
Malim, M.H. (2009) APOBEC proteins and intrinsic resistance to HIV-1 infection. Philosophical Transactions of the Royal Society of London Series B Biological Sciences 364, 675-687CrossRefGoogle ScholarPubMed
http://www.hiv.lanl.gov/content/sequence/HIV/mainpage.htmlGoogle Scholar
http://hivdb.stanford.edu/Google Scholar
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=rv.TOCGoogle Scholar
Chiu, Y.L. and Greene, W.C. (2008) The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annual Review of Immunology 26, 317-353CrossRefGoogle ScholarPubMed
Malim, M.H. and Emerman, M. (2008) HIV-1 accessory proteins–ensuring viral survival in a hostile environment. Cell Host and Microbe 3, 388-398CrossRefGoogle Scholar
Smith, J.L. et al. (2009) Multiple ways of targeting APOBEC3-virion infectivity factor interactions for anti-HIV-1 drug development. Trends in Pharmacological Sciences 30, 638-646CrossRefGoogle ScholarPubMed
Goila-Gaur, R. and Strebel, K. (2008) HIV-1 Vif, APOBEC, and intrinsic immunity. Retrovirology 5, 51CrossRefGoogle ScholarPubMed
Henriet, S. et al. (2009) Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC3G and APOBEC3F restriction factors. Microbiology and Molecular Biology Reviews 73, 211-232CrossRefGoogle ScholarPubMed
Malim, M.H. (2009) APOBEC proteins and intrinsic resistance to HIV-1 infection. Philosophical Transactions of the Royal Society of London Series B Biological Sciences 364, 675-687CrossRefGoogle ScholarPubMed
http://www.hiv.lanl.gov/content/sequence/HIV/mainpage.htmlGoogle Scholar
http://hivdb.stanford.edu/Google Scholar
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=rv.TOCGoogle Scholar