Advertisement

A Single Amino Acid in Human APOBEC3F Alters Susceptibility to HIV-1 Vif*

  • John S. Albin
    Footnotes
    Affiliations
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

    Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota 55455

    Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota 55455
    Search for articles by this author
  • Rebecca S. LaRue
    Footnotes
    Affiliations
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

    Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota 55455

    Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota 55455
    Search for articles by this author
  • Jessalyn A. Weaver
    Affiliations
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

    Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota 55455

    Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota 55455
    Search for articles by this author
  • William L. Brown
    Affiliations
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

    Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota 55455

    Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota 55455
    Search for articles by this author
  • Keisuke Shindo
    Affiliations
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

    Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota 55455

    Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota 55455
    Search for articles by this author
  • Elena Harjes
    Affiliations
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

    Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota 55455
    Search for articles by this author
  • Hiroshi Matsuo
    Affiliations
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

    Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota 55455
    Search for articles by this author
  • Reuben S. Harris
    Correspondence
    To whom correspondence should be addressed: 6-155 Jackson Hall, 321 Church St. S.E., Minneapolis, MN 55455. Tel.: 612-624-0457; Fax: 612-625-2163
    Affiliations
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

    Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota 55455

    Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota 55455
    Search for articles by this author
  • Author Footnotes
    * This work was supported, in whole or in part, by the National Institutes of Health Grant R01 AI064046 through the NIAID (to R. S. H.).
    The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.
    1 Supported by the National Institute on Drug Abuse (F30 DA026310) and the University of Minnesota Medical Scientist Training Program (T32 GM008244).
    2 Supported in part by a studentship from the Minnesota Agricultural Experiment Station and the College of Veterinary Medicine.
Open AccessPublished:October 22, 2010DOI:https://doi.org/10.1074/jbc.M110.173161
      Human APOBEC3F (huA3F) potently restricts the infectivity of HIV-1 in the absence of the viral accessory protein virion infectivity factor (Vif). Vif functions to preserve viral infectivity by triggering the degradation of huA3F but not rhesus macaque A3F (rhA3F). Here, we use a combination of deletions, chimeras, and systematic mutagenesis between huA3F and rhA3F to identify Glu324 as a critical determinant of huA3F susceptibility to HIV-1 Vif-mediated degradation. A structural model of the C-terminal deaminase domain of huA3F indicates that Glu324 is a surface residue within the α4 helix adjacent to residues corresponding to other known Vif susceptibility determinants in APOBEC3G and APOBEC3H. This structural clustering suggests that Vif may bind a conserved surface present in multiple APOBEC3 proteins.

      Introduction

      Human APOBEC3 proteins including APOBEC3F (huA3F) and APOBEC3G (huA3G) are DNA cytidine deaminases that restrict the infectivity of HIV-1 in target cells following virion incorporation in producer cells (recently reviewed in Refs.
      • Romani B.
      • Engelbrecht S.
      • Glashoff R.H.
      ,
      • Henriet S.
      • Mercenne G.
      • Bernacchi S.
      • Paillart J.C.
      • Marquet R.
      ,
      • Albin J.S.
      • Harris R.S.
      ). HIV-1 overcomes this restriction activity by utilizing its accessory protein virion infectivity factor (Vif)
      The abbreviations used are: Vif
      virion infectivity factor
      agm
      African green monkey
      CTD
      C-terminal deaminase domain
      hu
      human
      NTD
      N-terminal deaminase domain
      rh
      rhesus
      SIV
      simian immunodeficiency virus.
      to facilitate the degradation of APOBEC3 proteins in producer cells, thus preventing particle incorporation and restriction.
      Previously, several groups identified specific changes in the N-terminal deaminase domain (NTD) of huA3G that affect the ability of HIV-1 Vif to neutralize this restriction factor (
      • Mangeat B.
      • Turelli P.
      • Liao S.
      • Trono D.
      ,
      • Bogerd H.P.
      • Doehle B.P.
      • Wiegand H.L.
      • Cullen B.R.
      ,
      • Schröfelbauer B.
      • Chen D.
      • Landau N.R.
      ,
      • Xu H.
      • Svarovskaia E.S.
      • Barr R.
      • Zhang Y.
      • Khan M.A.
      • Strebel K.
      • Pathak V.K.
      ,
      • Huthoff H.
      • Malim M.H.
      ,
      • Russell R.A.
      • Smith J.
      • Barr R.
      • Bhattacharyya D.
      • Pathak V.K.
      ,
      • Lavens D.
      • Peelman F.
      • Van der Heyden J.
      • Uyttendaele I.
      • Catteeuw D.
      • Verhee A.
      • Van Schoubroeck B.
      • Kurth J.
      • Hallenberger S.
      • Clayton R.
      • Tavernier J.
      ). The first of these studies sought to determine the basis for the observation that the Vif proteins of the lentiviruses infecting different species neutralize the A3G proteins of their natural host species but not the A3G proteins of other species (
      • Mariani R.
      • Chen D.
      • Schröfelbauer B.
      • Navarro F.
      • König R.
      • Bollman B.
      • Münk C.
      • Nymark-McMahon H.
      • Landau N.R.
      ). For example, African green monkey A3G (agmA3G) is susceptible to Vif from the simian immunodeficiency virus (SIV) that naturally infects Chlorocebus aethiops (agmSIV) but not to HIV-1 Vif, whereas huA3G is susceptible to HIV-1 Vif but not to agmSIV Vif. By substituting agmA3G residues into huA3G where the two differed, several groups identified Asp128 as a critical determinant of this species specificity (
      • Mangeat B.
      • Turelli P.
      • Liao S.
      • Trono D.
      ,
      • Bogerd H.P.
      • Doehle B.P.
      • Wiegand H.L.
      • Cullen B.R.
      ,
      • Schröfelbauer B.
      • Chen D.
      • Landau N.R.
      ,
      • Xu H.
      • Svarovskaia E.S.
      • Barr R.
      • Zhang Y.
      • Khan M.A.
      • Strebel K.
      • Pathak V.K.
      ). Subsequent mutational analyses have confirmed that huA3G Asp128 and surrounding residues including Asp130 impact HIV-1 Vif-mediated degradation (
      • Huthoff H.
      • Malim M.H.
      ,
      • Russell R.A.
      • Smith J.
      • Barr R.
      • Bhattacharyya D.
      • Pathak V.K.
      ,
      • Lavens D.
      • Peelman F.
      • Van der Heyden J.
      • Uyttendaele I.
      • Catteeuw D.
      • Verhee A.
      • Van Schoubroeck B.
      • Kurth J.
      • Hallenberger S.
      • Clayton R.
      • Tavernier J.
      ).
      More recently, two reports showed that, in contrast with huA3G, huA3F is recognized at its C-terminal deaminase domain (CTD) by HIV-1 Vif (
      • Russell R.A.
      • Smith J.
      • Barr R.
      • Bhattacharyya D.
      • Pathak V.K.
      ,
      • Zhang W.
      • Chen G.
      • Niewiadomska A.M.
      • Xu R.
      • Yu X.F.
      ). One of these groups further narrowed the determinants of this recognition to amino acids 283–300, although individual amino acid changes critical for HIV-1 Vif susceptibility were not identified in a manner analogous to the huA3G studies cited above. Thus, the residues of huA3F critical for the ability of HIV-1 Vif to bind and degrade this restriction factor are presently unknown.
      Here, we identify a critical determinant of huA3F susceptibility to HIV-1 Vif by comparing huA3F with the closely related but HIV-1 Vif-resistant rhA3F (
      • Virgen C.A.
      • Hatziioannou T.
      ,
      • Zennou V.
      • Bieniasz P.D.
      ). Using chimeras between these orthologs as well as single-domain studies, we confirm that Vif recognizes the CTD of huA3F. Through systematic replacement of selected C-terminal huA3F residues with their corresponding rhA3F residues, we further identify huA3F Gln323/Glu324 as a critical determinant of this differential susceptibility. Additional mutagenesis between these two residues revealed that mutation of Glu324 to the rhA3F lysine or to alanine results in resistance to HIV-1 Vif-mediated degradation. To determine the three-dimensional context surrounding this residue, we created a model of the CTD of huA3F and found that Glu324 is a surface residue contained within the α4 helix that forms part of a broader surface shared with the linearly separate huA3F Vif interaction domain previously narrowed to residues 283–300 (
      • Russell R.A.
      • Smith J.
      • Barr R.
      • Bhattacharyya D.
      • Pathak V.K.
      ). Importantly, this analysis also revealed that the huA3F residues corresponding to three known Vif susceptibility determinants, Asp128 and Asp130 in huA3G and Asp/Glu121 in human APOBEC3H (huA3H), also cluster at this helix. These studies combine to suggest that a conserved structural surface is targeted by HIV-1 Vif en route to APOBEC3 neutralization and degradation.

      DISCUSSION

      The studies described here are the first to identify a single amino acid determinant of the susceptibility of huA3F to HIV-1 Vif. This represents an important advance in our understanding of the HIV-1 Vif-huA3F interaction, the relevance of which is strongly supported by a large body of work demonstrating the potency of huA3F-mediated restriction of HIV-1 (e.g.
      • Bishop K.N.
      • Holmes R.K.
      • Sheehy A.M.
      • Davidson N.O.
      • Cho S.J.
      • Malim M.H.
      ,
      • Liddament M.T.
      • Brown W.L.
      • Schumacher A.J.
      • Harris R.S.
      ,
      • Wiegand H.L.
      • Doehle B.P.
      • Bogerd H.P.
      • Cullen B.R.
      ,
      • Zheng Y.H.
      • Irwin D.
      • Kurosu T.
      • Tokunaga K.
      • Sata T.
      • Peterlin B.M.
      ). Our own long term viral evolution studies have also suggested that functional neutralization of huA3F by HIV-1 Vif is required for the virus propagate in the presence of huA3F (
      • Albin J.S.
      • Haché G.
      • Hultquist J.F.
      • Brown W.L.
      • Harris R.S.
      ). Thus, shielding the α4 region of huA3F described here from HIV-1 Vif may represent a viable strategy for the development of novel pharmacotherapies for HIV-1 infection (
      • Albin J.S.
      • Harris R.S.
      ,
      • Harris R.S.
      • Liddament M.T.
      ).
      Our work confirms prior reports that broadly localized Vif interaction to the CTD of huA3F (
      • Russell R.A.
      • Smith J.
      • Barr R.
      • Bhattacharyya D.
      • Pathak V.K.
      ,
      • Zhang W.
      • Chen G.
      • Niewiadomska A.M.
      • Xu R.
      • Yu X.F.
      ) (Fig. 1). An additional recent report on the existence of a Vif-susceptible splice variant of huA3F composed largely of the CTD is also consistent with these data (
      • Lassen K.G.
      • Wissing S.
      • Lobritz M.A.
      • Santiago M.
      • Greene W.C.
      ).
      Our identification of a single amino acid determinant of HIV-1 Vif susceptibility in huA3F echoes several prior reports localizing Vif susceptibility in huA3G and huA3H in that the residue identified is a single negative charge localized to the surface of an APOBEC3 protein (
      • Mangeat B.
      • Turelli P.
      • Liao S.
      • Trono D.
      ,
      • Bogerd H.P.
      • Doehle B.P.
      • Wiegand H.L.
      • Cullen B.R.
      ,
      • Schröfelbauer B.
      • Chen D.
      • Landau N.R.
      ,
      • Xu H.
      • Svarovskaia E.S.
      • Barr R.
      • Zhang Y.
      • Khan M.A.
      • Strebel K.
      • Pathak V.K.
      ) (FIGURE 4, FIGURE 5). Glu324 differs from these reports in one key respect, however, as a charge substitution was involved in all prior reports. For example, huA3G D128A has no phenotype, whereas D128K is Vif-resistant (e.g.
      • Bogerd H.P.
      • Doehle B.P.
      • Wiegand H.L.
      • Cullen B.R.
      ,
      • Schröfelbauer B.
      • Chen D.
      • Landau N.R.
      ,
      • Huthoff H.
      • Malim M.H.
      ). The fact that both alanine and lysine substitutions at huA3F Glu324 ablate Vif susceptibility (Fig. 4A) suggests that Glu324 is required either for overall stability of the broader Vif binding surface or for direct functional interaction with HIV-1 Vif. Changes to this residue do not, however, affect the ability of huA3F to restrict HIV-1; in fact, none of the changes described in these studies affected restriction activity (e.g. FIGURE 2, FIGURE 3, FIGURE 4).
      It is notable that Glu324 does not fall within the region previously found by Russell et al. to be critical for HIV-1 Vif recognition of huA3F (
      • Russell R.A.
      • Smith J.
      • Barr R.
      • Bhattacharyya D.
      • Pathak V.K.
      ). These residues, 283–300, encompass most of the α3 helix, which is structurally adjacent to α4 and Glu324 and appears to form a common surface (Fig. 5, A and B) (
      • Russell R.A.
      • Smith J.
      • Barr R.
      • Bhattacharyya D.
      • Pathak V.K.
      ). It is therefore possible that Glu324 may cooperate with residues in α3 and/or α4 to create a stable surface recognized by HIV-1 Vif, in which case mutational alteration of any critical component of this putative Vif interaction node may affect Vif sensitivity. Alternatively, Russell et al. used chimeras between huA3F and huA3G to map the huA3F Vif-interacting region (
      • Russell R.A.
      • Smith J.
      • Barr R.
      • Bhattacharyya D.
      • Pathak V.K.
      ). The CTDs of huA3F and huA3G, however, are evolutionarily divergent Z2 and Z1 types, respectively (
      • LaRue R.S.
      • Andrésdóttir V.
      • Blanchard Y.
      • Conticello S.G.
      • Derse D.
      • Emerman M.
      • Greene W.C.
      • Jónsson S.R.
      • Landau N.R.
      • Löchelt M.
      • Malik H.S.
      • Malim M.H.
      • Münk C.
      • O'Brien S.J.
      • Pathak V.K.
      • Strebel K.
      • Wain-Hobson S.
      • Yu X.F.
      • Yuhki N.
      • Harris R.S.
      ). This means that chimeras in this domain will contain a relatively large number of amino acid substitutions versus wild type. For example, only half of residues 283–300 are biochemically similar or identical between huA3F and huA3G. Thus, we think it likely that the structure of huA3F/huA3G chimeras in this region will be altered relative to huA3F, which may affect interaction with Vif.
      In addition to suggesting the structural unity of our findings with those of Russell et al., our model of the huA3F CTD allowed us to make an important observation about the nature of the region surrounding Glu324; namely, both the α4 and the neighboring α3 helices have a number of negatively charged surface residues (Fig. 5, A and B). This led us to align these surface residues with those in other Vif-susceptible APOBEC3 deaminase domains such as the huA3G NTD and huA3H, which showed that each negatively charged surface residue in the α4 helix of huA3F corresponds to a known negatively charged determinant of Vif susceptibility in another APOBEC3 protein (Fig. 5). Thus, although determining the identity of all the amino acid residues with which Vif interacts (i.e. the broader Vif binding surface in APOBEC3 proteins) will require a great deal of future genetic and structural study, it is intriguing that all known Vif susceptibility determinants map to the same structural motif. This implies a degree of structural conservation among Vif-APOBEC3 interaction surfaces that would not be apparent from a simple linear comparison of these single amino acid determinants.
      Although the lack of functional interaction between Vif and huA3F Glu324 variants is clear, this appears to be due to a qualitative change in the nature of the Vif-huA3F interaction in Glu324 mutants because coimmunoprecipitation of huA3F Glu324 mutants with HIV-1 Vif is unimpaired. Our data therefore support the potential for both qualitative and quantitative changes in huA3F binding to Vif that may alter susceptibility. In the absence of structural data, however, we are unable to explain the nature of the qualitative defect found in huA3F Glu324 mutants. It is possible that the qualitative defect in Glu324 mutants may involve a conformational change that prevents productive interaction with HIV-1 Vif. Alternatively, mutation of Glu324 may impair the recruitment of other components of the E3 ligase complex by HIV-1 Vif en route to degradation. It is also conceivable that Glu324 mutants may have a functionally relevant, altered affinity for HIV-1 Vif that is not readily apparent by coimmunoprecipitation.
      In summary, we have described here a single amino acid determinant of huA3F susceptibility to HIV-1 Vif. This advance in our understanding of the Vif-huA3F interaction echoes the single amino acid determinants previously identified in other APOBEC3 proteins, as all are negatively charged residues that may interact directly with the highly basic Vif protein. Importantly, the observation that all of these single amino acid determinants cluster along the α4 helix raises the exciting possibility that certain features of the Vif-APOBEC3 interaction may be structurally conserved, which would facilitate the design of hypothetical single molecules which may simultaneously block the functional interaction of Vif with multiple APOBEC3 proteins. Indeed, although its exact mechanism of action remains unknown, the compound RN-18 provides proof of concept for just such a scenario (
      • Nathans R.
      • Cao H.
      • Sharova N.
      • Ali A.
      • Sharkey M.
      • Stranska R.
      • Stevenson M.
      • Rana T.M.
      ).

      Acknowledgments

      We thank T. Hatziioannou, P. Bieniasz, X.F. Yu and the AIDS Research and Reference Reagent Program for materials, D. Urso for technical assistance, L. Lackey for helpful discussion and L. Mansky for sharing flow cytometry facilities.

      REFERENCES

        • Romani B.
        • Engelbrecht S.
        • Glashoff R.H.
        Arch. Virol. 2009; 154: 1579-1588
        • Henriet S.
        • Mercenne G.
        • Bernacchi S.
        • Paillart J.C.
        • Marquet R.
        Microbiol. Mol. Biol. Rev. 2009; 73: 211-232
        • Albin J.S.
        • Harris R.S.
        Expert Rev. Mol. Med. 2010; 12: 1-26
        • Mangeat B.
        • Turelli P.
        • Liao S.
        • Trono D.
        J. Biol. Chem. 2004; 279: 14481-14483
        • Bogerd H.P.
        • Doehle B.P.
        • Wiegand H.L.
        • Cullen B.R.
        Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 3770-3774
        • Schröfelbauer B.
        • Chen D.
        • Landau N.R.
        Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 3927-3932
        • Xu H.
        • Svarovskaia E.S.
        • Barr R.
        • Zhang Y.
        • Khan M.A.
        • Strebel K.
        • Pathak V.K.
        Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 5652-5657
        • Huthoff H.
        • Malim M.H.
        J. Virol. 2007; 81: 3807-3815
        • Russell R.A.
        • Smith J.
        • Barr R.
        • Bhattacharyya D.
        • Pathak V.K.
        J. Virol. 2009; 83: 1992-2003
        • Lavens D.
        • Peelman F.
        • Van der Heyden J.
        • Uyttendaele I.
        • Catteeuw D.
        • Verhee A.
        • Van Schoubroeck B.
        • Kurth J.
        • Hallenberger S.
        • Clayton R.
        • Tavernier J.
        Nucleic Acids Res. 2010; 38: 1902-1912
        • Mariani R.
        • Chen D.
        • Schröfelbauer B.
        • Navarro F.
        • König R.
        • Bollman B.
        • Münk C.
        • Nymark-McMahon H.
        • Landau N.R.
        Cell. 2003; 114: 21-31
        • Zhang W.
        • Chen G.
        • Niewiadomska A.M.
        • Xu R.
        • Yu X.F.
        PLoS ONE. 2008; 3: e3963
        • Virgen C.A.
        • Hatziioannou T.
        J. Virol. 2007; 81: 13932-13937
        • Zennou V.
        • Bieniasz P.D.
        Virology. 2006; 349: 31-40
        • Albin J.S.
        • Haché G.
        • Hultquist J.F.
        • Brown W.L.
        • Harris R.S.
        J. Virol. 2010; 84: 10209-10219
        • LaRue R.S.
        • Jónsson S.R.
        • Silverstein K.A.
        • Lajoie M.
        • Bertrand D.
        • El-Mabrouk N.
        • Hötzel I.
        • Andrésdóttir V.
        • Smith T.P.
        • Harris R.S.
        BMC Mol. Biol. 2008; 9: 104-224
        • Stenglein M.D.
        • Harris R.S.
        J. Biol. Chem. 2006; 281: 16837-16841
        • LaRue R.S.
        • Lengyel J.A.
        • Jónsson S.R.
        • Andrésdóttir V.
        • Harris R.S.
        J. Virol. 2010; 84: 8193-8201
        • Gibbs J.S.
        • Regier D.A.
        • Desrosiers R.C.
        AIDS Res. Human Retroviruses. 1994; 10: 343-350
        • Haché G.
        • Shindo K.
        • Albin J.S.
        • Harris R.S.
        Curr. Biol. 2008; 18: 819-824
        • Gervaix A.
        • West D.
        • Leoni L.M.
        • Richman D.D.
        • Wong-Staal F.
        • Corbeil J.
        Proc. Natl. Acad. Sci. U.S.A. 1997; 94: 4653-4658
        • Krieger E.
        • Koraimann G.
        • Vriend G.
        Proteins. 2002; 47: 393-402
        • Shandilya S.M.
        • Nalam M.N.
        • Nalivaika E.A.
        • Gross P.J.
        • Valesano J.C.
        • Shindo K.
        • Li M.
        • Munson M.
        • Royer W.E.
        • Harjes E.
        • Kono T.
        • Matsuo H.
        • Harris R.S.
        • Somasundaran M.
        • Schiffer C.A.
        Structure. 2010; 18: 28-38
        • Nathans R.
        • Cao H.
        • Sharova N.
        • Ali A.
        • Sharkey M.
        • Stranska R.
        • Stevenson M.
        • Rana T.M.
        Nat. Biotechnol. 2008; 26: 1187-1192
        • LaRue R.S.
        • Andrésdóttir V.
        • Blanchard Y.
        • Conticello S.G.
        • Derse D.
        • Emerman M.
        • Greene W.C.
        • Jónsson S.R.
        • Landau N.R.
        • Löchelt M.
        • Malik H.S.
        • Malim M.H.
        • Münk C.
        • O'Brien S.J.
        • Pathak V.K.
        • Strebel K.
        • Wain-Hobson S.
        • Yu X.F.
        • Yuhki N.
        • Harris R.S.
        J. Virol. 2009; 83: 494-497
        • Browne E.P.
        • Allers C.
        • Landau N.R.
        Virology. 2009; 387: 313-321
        • Miyagi E.
        • Opi S.
        • Takeuchi H.
        • Khan M.
        • Goila-Gaur R.
        • Kao S.
        • Strebel K.
        J. Virol. 2007; 81: 13346-13353
        • Schumacher A.J.
        • Haché G.
        • MacDuff D.A.
        • Brown W.L.
        • Harris R.S.
        J. Virol. 2008; 82: 2652-2660
        • Refsland E.W.
        • Stenglein M.D.
        • Shindo K.
        • Albin J.S.
        • Brown W.L.
        • Harris R.S.
        Nucleic Acids Res. 2010; 38: 4274-4284
        • Zhen A.
        • Wang T.
        • Zhao K.
        • Xiong Y.
        • Yu X.F.
        J. Virol. 2010; 84: 1902-1911
        • Bishop K.N.
        • Holmes R.K.
        • Sheehy A.M.
        • Davidson N.O.
        • Cho S.J.
        • Malim M.H.
        Curr. Biol. 2004; 14: 1392-1396
        • Liddament M.T.
        • Brown W.L.
        • Schumacher A.J.
        • Harris R.S.
        Curr. Biol. 2004; 14: 1385-1391
        • Wiegand H.L.
        • Doehle B.P.
        • Bogerd H.P.
        • Cullen B.R.
        EMBO J. 2004; 23: 2451-2458
        • Zheng Y.H.
        • Irwin D.
        • Kurosu T.
        • Tokunaga K.
        • Sata T.
        • Peterlin B.M.
        J. Virol. 2004; 78: 6073-6076
        • Harris R.S.
        • Liddament M.T.
        Nat. Rev. Immunol. 2004; 4: 868-877
        • Lassen K.G.
        • Wissing S.
        • Lobritz M.A.
        • Santiago M.
        • Greene W.C.
        J. Biol. Chem. 2010; 285: 29326-29335