1887

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Volume 98, Issue 9

Moderate sensitivity of mouse mammary tumour virus to inhibition by human APOBEC3G Free

Abstract

Infectivity of the mouse mammary tumour virus (MMTV) is inhibited by mouse APOBEC3 (mA3) which is efficiently packaged into virions. As the inhibition is only partial, the virus can replicate in tissues expressing mA3 and complete its replication cycle. Here, we have examined the sensitivity of MMTV to inhibition by a human orthologue of mA3, A3G. We report that the virus containing A3G is only moderately susceptible to inhibition by the human factor. Whereas the -deficient HIV-1 vector produced in human epithelial cells expressing endogenous levels of A3G was efficiently inhibited, an MMTV vector remained fully infectious. Greater A3G expression levels were necessary to restrict infectivity of MMTV, but only when the factor retained its deaminase activity. Furthermore, the spreading kinetic of a replication competent MMTV was only moderately accelerated in cells with downmodulated A3G expression. These data suggest that MMTV has evolved a mechanism to neutralize antiviral activity of APOBEC3 proteins.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): APOBEC3 , betaretrovirus , innate immunity , mouse mammary tumor virus and resistance MMTV
© 2017 The Authors
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2017-09-01
2024-04-25
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References

  1. Sheehy AM, Gaddis NC, Malim MH. The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med 2003; 9:1404–1407 [View Article][PubMed]
     [Google Scholar]
  2. Okeoma CM, Lovsin N, Peterlin BM, Ross SR. APOBEC3 inhibits mouse mammary tumour virus replication in vivo. Nature 2007; 445:927–930 [View Article][PubMed]
     [Google Scholar]
  3. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK et al. DNA deamination mediates innate immunity to retroviral infection. Cell 2003; 113:803–809 [View Article][PubMed]
     [Google Scholar]
  4. Bishop KN, Holmes RK, Sheehy AM, Davidson NO, Cho SJ et al. Cytidine deamination of retroviral DNA by diverse APOBEC proteins. Curr Biol 2004; 14:1392–1396 [View Article][PubMed]
     [Google Scholar]
  5. Mangeat B, Turelli P, Caron G, Friedli M, Perrin L et al. Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 2003; 424:99–103 [View Article][PubMed]
     [Google Scholar]
  6. Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC et al. The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 2003; 424:94–98 [View Article][PubMed]
     [Google Scholar]
  7. Macmillan AL, Kohli RM, Ross SR. APOBEC3 inhibition of mouse mammary tumor virus infection: the role of cytidine deamination versus inhibition of reverse transcription. J Virol 2013; 87:4808–4817 [View Article][PubMed]
     [Google Scholar]
  8. Bishop KN, Verma M, Kim EY, Wolinsky SM, Malim MH. APOBEC3G inhibits elongation of HIV-1 reverse transcripts. PLoS Pathog 2008; 4:e1000231 [View Article][PubMed]
     [Google Scholar]
  9. Iwatani Y, Chan DS, Wang F, Maynard KS, Sugiura W et al. Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G. Nucleic Acids Res 2007; 35:7096–7108 [View Article][PubMed]
     [Google Scholar]
  10. Mbisa JL, Bu W, Pathak VK. APOBEC3F and APOBEC3G inhibit HIV-1 DNA integration by different mechanisms. J Virol 2010; 84:5250–5259 [View Article][PubMed]
     [Google Scholar]
  11. Okeoma CM, Huegel AL, Lingappa J, Feldman MD, Ross SR. APOBEC3 proteins expressed in mammary epithelial cells are packaged into retroviruses and can restrict transmission of milk-borne virions. Cell Host Microbe 2010; 8:534–543 [View Article][PubMed]
     [Google Scholar]
  12. Konstantoulas CJ, Indik S. C3H strain of mouse mammary tumour virus, like GR strain, infects human mammary epithelial cells, albeit less efficiently than murine mammary epithelial cells. J Gen Virol 2015; 96:650–662 [View Article][PubMed]
     [Google Scholar]
  13. Indik S, Günzburg WH, Kulich P, Salmons B, Rouault F. Rapid spread of mouse mammary tumor virus in cultured human breast cells. Retrovirology 2007; 4:73 [View Article][PubMed]
     [Google Scholar]
  14. Indik S, Günzburg WH, Salmons B, Rouault F. Mouse mammary tumor virus infects human cells. Cancer Res 2005; 65:6651–6659 [View Article][PubMed]
     [Google Scholar]
  15. Konstantoulas CJ, Indik S. Mouse mammary tumor virus-based vector transduces non-dividing cells, enters the nucleus via a TNPO3-independent pathway and integrates in a less biased fashion than other retroviruses. Retrovirology 2014; 11:34 [View Article][PubMed]
     [Google Scholar]
  16. Aguiar RS, Peterlin BM. APOBEC3 proteins and reverse transcription. Virus Res 2008; 134:74–85 [View Article][PubMed]
     [Google Scholar]
  17. Newman EN, Holmes RK, Craig HM, Klein KC, Lingappa JR et al. Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity. Curr Biol 2005; 15:166–170 [View Article][PubMed]
     [Google Scholar]
  18. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M et al. A third-generation lentivirus vector with a conditional packaging system. J Virol 1998; 72:8463–8471[PubMed]
     [Google Scholar]
  19. Yu Q, König R, Pillai S, Chiles K, Kearney M et al. Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol 2004; 11:435–442 [View Article][PubMed]
     [Google Scholar]
  20. Cullen BR. Role and mechanism of action of the APOBEC3 family of antiretroviral resistance factors. J Virol 2006; 80:1067–1076 [View Article][PubMed]
     [Google Scholar]
  21. Derse D, Hill SA, Princler G, Lloyd P, Heidecker G. Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid. Proc Natl Acad Sci USA 2007; 104:2915–2920 [View Article][PubMed]
     [Google Scholar]
  22. Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 2002; 418:646–650 [View Article][PubMed]
     [Google Scholar]
  23. Doehle BP, Bogerd HP, Wiegand HL, Jouvenet N, Bieniasz PD et al. The betaretrovirus Mason-Pfizer monkey virus selectively excludes simian APOBEC3G from virion particles. J Virol 2006; 80:12102–12108 [View Article][PubMed]
     [Google Scholar]
  24. Russell RA, Wiegand HL, Moore MD, Schäfer A, McClure MO et al. Foamy virus Bet proteins function as novel inhibitors of the APOBEC3 family of innate antiretroviral defense factors. J Virol 2005; 79:8724–8731 [View Article][PubMed]
     [Google Scholar]
  25. Löchelt M, Romen F, Bastone P, Muckenfuss H, Kirchner N et al. The antiretroviral activity of APOBEC3 is inhibited by the foamy virus accessory Bet protein. Proc Natl Acad Sci USA 2005; 102:7982–7987 [View Article][PubMed]
     [Google Scholar]
  26. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 2001; 25:402–408 [View Article][PubMed]
     [Google Scholar]
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Moderate sensitivity of mouse mammary tumour virus to inhibition by human APOBEC3G
J. Gen. Virol. 98, 2362 (2017); https://doi.org/10.1099/jgv.0.000897
/content/journal/jgv/10.1099/jgv.0.000897
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