1887

Abstract

APOBEC3 (A3) proteins are host-encoded restriction factors that inhibit retrovirus infection by mutagenic deamination of cytosines in minus-strand DNA replication intermediates. APOBEC3F (A3F) and APOBEC3G (A3G) are two of the most potent A3 enzymes in humans with each having a different target DNA specificity. A3G prefers to deaminate cytosines preceded by a cytosine (5′-C), whereas A3F preferentially targets cytosines preceded by a thymine (5′-T). Here we performed a detailed comparative analysis of retrovirus-encoded gene sequences edited by A3F and A3G, with the aim of correlating the context and intensity of the mutations with their effects on gene function. Our results revealed that, when there are few (TGG) tryptophan codons in the sequence, both enzymes alter gene function with a similar efficiency when given equal opportunities to deaminate in their preferred target DNA context. In contrast, tryptophan-rich genes are efficiently inactivated in the presence of a low mutational burden, through termination codon generation by A3G but not A3F. Overall, our results clearly demonstrated that the target DNA specificity of an A3 enzyme along with the intensity of the mutational burden and the tryptophan content of the gene being targeted are the factors that have the most forceful influence on whether A3-induced mutations will favour either terminal inactivation or genetic diversification of a retrovirus.

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2015-09-01
2021-10-27
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References

  1. Albin J.S., Brown W.L., Harris R.S. 2014; Catalytic activity of APOBEC3F is required for efficient restriction of Vif-deficient human immunodeficiency virus. Virology 450-451:49–54 [View Article][PubMed]
    [Google Scholar]
  2. Ara A., Love R.P., Chelico L. 2014; Different mutagenic potential of HIV-1 restriction factors APOBEC3G and APOBEC3F is determined by distinct single-stranded DNA scanning mechanisms. PLoS Pathog 10:e1004024 [View Article][PubMed]
    [Google Scholar]
  3. Armitage A.E., Deforche K., Chang C.H., Wee E., Kramer B., Welch J.J., Gerstoft J., Fugger L., McMichael A., other authors. 2012; APOBEC3G-induced hypermutation of human immunodeficiency virus type-1 is typically a discrete all or nothing phenomenon. PLoS Genet 8:e1002550 [View Article][PubMed]
    [Google Scholar]
  4. Armitage A.E., Deforche K., Welch J.J., Van Laethem K., Camacho R., Rambaut A., Iversen A.K. 2014; Possible footprints of APOBEC3F and/or other APOBEC3 deaminases, but not APOBEC3G, on HIV-1 from patients with acute/early and chronic infections. J Virol 88:12882–12894 [View Article][PubMed]
    [Google Scholar]
  5. Arpino J.A., Rizkallah P.J., Jones D.D. 2012; Crystal structure of enhanced green fluorescent protein to 1.35 Å resolution reveals alternative conformations for Glu222. PLoS One 7:e47132 [View Article][PubMed]
    [Google Scholar]
  6. Bélanger K., Savoie M., Rosales Gerpe M.C., Couture J.F., Langlois M.A. 2013; Binding of RNA by APOBEC3G controls deamination-independent restriction of retroviruses. Nucleic Acids Res 41:7438–7452 [View Article][PubMed]
    [Google Scholar]
  7. Bélanger K., Savoie M., Aydin H., Renner T.M., Montazeri Z., Langlois M.A. 2014; Deamination intensity profiling of human APOBEC3 protein activity along the near full-length genomes of HIV-1 and MoMLV by HyperHRM analysis. Virology 448:168–175 [View Article][PubMed]
    [Google Scholar]
  8. Bogerd H.P., Wiegand H.L., Doehle B.P., Cullen B.R. 2007; The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active cytidine deaminase domains. Virology 364:486–493 [View Article][PubMed]
    [Google Scholar]
  9. Browne E.P., Allers C., Landau N.R. 2009; Restriction of HIV-1 by APOBEC3G is cytidine deaminase-dependent. Virology 387:313–321 [View Article][PubMed]
    [Google Scholar]
  10. Chelico L., Pham P., Calabrese P., Goodman M.F. 2006; APOBEC3G DNA deaminase acts processively 3′ -> 5′-on single-stranded DNA. Nat Struct Mol Biol 13:392–399 [View Article][PubMed]
    [Google Scholar]
  11. Derdeyn C.A., Decker J.M., Sfakianos J.N., Wu X., O'Brien W.A., Ratner L., Kappes J.C., Shaw G.M., Hunter E. 2000; Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120. J Virol 74:8358–8367 [View Article][PubMed]
    [Google Scholar]
  12. Desimmie B.A., Delviks-Frankenberrry K.A., Burdick R.C., Qi D., Izumi T., Pathak V.K. 2014; Multiple APOBEC3 restriction factors for HIV-1 and one Vif to rule them all. J Mol Biol 426:1220–1245 [View Article][PubMed]
    [Google Scholar]
  13. Feng Y., Baig T.T., Love R.P., Chelico L. 2014; Suppression of APOBEC3-mediated restriction of HIV-1 by Vif. Front Microbiol 5:450 [View Article][PubMed]
    [Google Scholar]
  14. Fourati S., Lambert-Niclot S., Soulie C., Malet I., Valantin M.A., Descours B., Ait-Arkoub Z., Mory B., Carcelain G., other authors. 2012a; HIV-1 genome is often defective in PBMCs and rectal tissues after long-term HAART as a result of APOBEC3 editing and correlates with the size of reservoirs. J Antimicrob Chemother 67:2323–2326 [View Article][PubMed]
    [Google Scholar]
  15. Fourati S., Malet I., Lambert S., Soulie C., Wirden M., Flandre P., Fofana D.B., Sayon S., Simon A., other authors. 2012b; E138K and M184I mutations in HIV-1 reverse transcriptase coemerge as a result of APOBEC3 editing in the absence of drug exposure. AIDS 26:1619–1624 [View Article][PubMed]
    [Google Scholar]
  16. Gervaix A., West D., Leoni L.M., Richman D.D., Wong-Staal F., Corbeil J. 1997; A new reporter cell line to monitor HIV infection and drug susceptibility in vitro. Proc Natl Acad Sci U S A 94:4653–4658 [View Article][PubMed]
    [Google Scholar]
  17. Haché G., Mansky L.M., Harris R.S. 2006; Human APOBEC3 proteins, retrovirus restriction, and HIV drug resistance. AIDS Rev 8:148–157[PubMed]
    [Google Scholar]
  18. Harris R.S., Dudley J.P. 2015; APOBECs and virus restriction. Virology 479:(480C)131–145 [View Article][PubMed]
    [Google Scholar]
  19. Hultquist J.F., Lengyel J.A., Refsland E.W., LaRue R.S., Lackey L., Brown W.L., Harris R.S. 2011; Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1. J Virol 85:11220–11234 [View Article][PubMed]
    [Google Scholar]
  20. Jern P., Russell R.A., Pathak V.K., Coffin J.M. 2009; Likely role of APOBEC3G-mediated G-to-A mutations in HIV-1 evolution and drug resistance. PLoS Pathog 5:e1000367 [View Article][PubMed]
    [Google Scholar]
  21. Kim E.Y., Lorenzo-Redondo R., Little S.J., Chung Y.S., Phalora P.K., Maljkovic Berry I., Archer J., Penugonda S., Fischer W., other authors. 2014; Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection. PLoS Pathog 10:e1004281 [View Article][PubMed]
    [Google Scholar]
  22. Kobayashi M., Takaori-Kondo A., Miyauchi Y., Iwai K., Uchiyama T. 2005; Ubiquitination of APOBEC3G by an HIV-1 Vif-Cullin5-Elongin B-Elongin C complex is essential for Vif function. J Biol Chem 280:18573–18578 [View Article][PubMed]
    [Google Scholar]
  23. Kobayashi T., Koizumi Y., Takeuchi J.S., Misawa N., Kimura Y., Morita S., Aihara K., Koyanagi Y., Iwami S., Sato K. 2014; Quantification of deaminase activity-dependent and -independent restriction of HIV-1 replication mediated by APOBEC3F and APOBEC3G through experimental-mathematical investigation. J Virol 88:5881–5887 [View Article][PubMed]
    [Google Scholar]
  24. Koito A., Ikeda T. 2013; Intrinsic immunity against retrotransposons by APOBEC cytidine deaminases. Front Microbiol 4:28 [View Article][PubMed]
    [Google Scholar]
  25. Langlois M.A., Beale R.C., Conticello S.G., Neuberger M.S. 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 Res 33:1913–1923 [View Article][PubMed]
    [Google Scholar]
  26. Langlois M.-A., Kemmerich K., Rada C., Neuberger M.S. 2009; The AKV murine leukemia virus is restricted and hypermutated by mouse APOBEC3. J Virol 83:11550–11559 [View Article][PubMed]
    [Google Scholar]
  27. Liu B., Yu X., Luo K., Yu Y., Yu X.F. 2004; Influence of primate lentiviral Vif and proteasome inhibitors on human immunodeficiency virus type 1 virion packaging of APOBEC3G. J Virol 78:2072–2081 [View Article][PubMed]
    [Google Scholar]
  28. Love R.P., Xu H., Chelico L. 2012; Biochemical analysis of hypermutation by the deoxycytidine deaminase APOBEC3A. J Biol Chem 287:30812–30822 [View Article][PubMed]
    [Google Scholar]
  29. Mehle A., Strack B., Ancuta P., Zhang C., McPike M., Gabuzda D. 2004; Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway. J Biol Chem 279:7792–7798 [View Article][PubMed]
    [Google Scholar]
  30. Miyagi E., Opi S., Takeuchi H., Khan M., Goila-Gaur R., Kao S., Strebel K. 2007; Enzymatically active APOBEC3G is required for efficient inhibition of human immunodeficiency virus type 1. J Virol 81:13346–13353 [View Article][PubMed]
    [Google Scholar]
  31. Monajemi M., Woodworth C.F., Benkaroun J., Grant M., Larijani M. 2012; Emerging complexities of APOBEC3G action on immunity and viral fitness during HIV infection and treatment. Retrovirology 9:35 [View Article][PubMed]
    [Google Scholar]
  32. Monajemi M., Woodworth C.F., Zipperlen K., Gallant M., Grant M.D., Larijani M. 2014; Positioning of APOBEC3G/F mutational hotspots in the human immunodeficiency virus genome favors reduced recognition by CD8+T cells. PLoS One 9:e93428 [View Article][PubMed]
    [Google Scholar]
  33. Mulder L.C., Harari A., Simon V. 2008; Cytidine deamination induced HIV-1 drug resistance. Proc Natl Acad Sci U S A 105:5501–5506 [View Article][PubMed]
    [Google Scholar]
  34. Neogi U., Shet A., Sahoo P.N., Bontell I., Ekstrand M.L., Banerjea A.C., Sonnerborg A. 2013; Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. J Int AIDS Soc 16:18472 [View Article][PubMed]
    [Google Scholar]
  35. Platt E.J., Wehrly K., Kuhmann S.E., Chesebro B., Kabat D. 1998; Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. J Virol 72:2855–2864[PubMed]
    [Google Scholar]
  36. Rausch J.W., Chelico L., Goodman M.F., Le Grice S.F. 2009; Dissecting APOBEC3G substrate specificity by nucleoside analog interference. J Biol Chem 284:7047–7058 [View Article][PubMed]
    [Google Scholar]
  37. Sadler H.A., Stenglein M.D., Harris R.S., Mansky L.M. 2010; APOBEC3G contributes to HIV-1 variation through sublethal mutagenesis. J Virol 84:7396–7404 [View Article][PubMed]
    [Google Scholar]
  38. Sato K., Takeuchi J.S., Misawa N., Izumi T., Kobayashi T., Kimura Y., Iwami S., Takaori-Kondo A., Hu W.S., other authors. 2014; APOBEC3D and APOBEC3F potently promote HIV-1 diversification and evolution in humanized mouse model. PLoS Pathog 10:e1004453 [View Article][PubMed]
    [Google Scholar]
  39. Simon V., Zennou V., Murray D., Huang Y., Ho D.D., Bieniasz P.D. 2005; Natural variation in Vif: differential impact on APOBEC3G/3F and a potential role in HIV-1 diversification. PLoS Pathog 1:e6 [View Article][PubMed]
    [Google Scholar]
  40. Sliva K., Erlwein O., Bittner A., Schnierle B.S. 2004; Murine leukemia virus (MLV) replication monitored with fluorescent proteins. Virol J 1:14 [View Article][PubMed]
    [Google Scholar]
  41. Strebel K. 2013; HIV accessory proteins versus host restriction factors. Curr Opin Virol 3:692–699 [View Article][PubMed]
    [Google Scholar]
  42. Suspène R., Rusniok C., Vartanian J.P., Wain-Hobson S. 2006; Twin gradients in APOBEC3 edited HIV-1 DNA reflect the dynamics of lentiviral replication. Nucleic Acids Res 34:4677–4684 [View Article][PubMed]
    [Google Scholar]
  43. Wood N., Bhattacharya T., Keele B.F., Giorgi E., Liu M., Gaschen B., Daniels M., Ferrari G., Haynes B.F., other authors. 2009; HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC. PLoS Pathog 5:e1000414 [View Article][PubMed]
    [Google Scholar]
  44. Yu X., Yu Y., Liu B., Luo K., Kong W., Mao P., Yu X.F. 2003; Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science 302:1056–1060 [View Article][PubMed]
    [Google Scholar]
  45. Yu Q., König R., Pillai S., Chiles K., Kearney M., Palmer S., Richman D., Coffin J.M., Landau N.R. 2004; Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol 11:435–442 [View Article][PubMed]
    [Google Scholar]
  46. Zennou V., Bieniasz P.D. 2006; Comparative analysis of the antiretroviral activity of APOBEC3G and APOBEC3F from primates. Virology 349:31–40 [View Article][PubMed]
    [Google Scholar]
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