Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1 activities

Retrovirology

Judith G Levin⁴  Yasumasa Iwatani²  Angela M Gronenborn¹  In-Ja L Byeon¹  Robert J Gorelick³  Gabriel Nam⁴  Jozef Hritz⁵  Yu Mano²  Dustin Singer⁴  Mithun Mitra⁶ 

[1] Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh Medical School, Pittsburgh 15261, PA, USA;Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya 460-0001, Aichi, Japan;AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick 21702-1201, MD, USA;Section on Viral Gene Regulation, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda 20892-2780, MD, USA;Department of Structural Biology, CEITEC, Masaryk University, Kamenice 5, Brno, 625 00, Czech Republic;Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles 90095, CA, USA

关键词: Reverse transcription;    Deaminase-independent restriction;    Antiviral activity;    Deaminase activity;    Homology model;    APOBEC3H;    HIV-1;   

Others  :  1131993
DOI  :  10.1186/s12977-014-0130-8

 received in 2014-10-14, accepted in 2014-12-17,  发布年份 2015

【 摘 要 】

Background

Human APOBEC3H (A3H) belongs to the A3 family of host restriction factors, which are cytidine deaminases that catalyze conversion of deoxycytidine to deoxyuridine in single-stranded DNA. A3 proteins contain either one (A3A, A3C, A3H) or two (A3B, A3D, A3F, A3G) Zn-binding domains. A3H has seven haplotypes (I-VII) that exhibit diverse biological phenotypes and geographical distribution in the human population. Its single Zn-coordinating deaminase domain belongs to a phylogenetic cluster (Z3) that is different from the Z1- and Z2-type domains in other human A3 proteins. A3H HapII, unlike A3A or A3C, has potent activity against HIV-1. Here, we sought to identify the determinants of A3H HapII deaminase and antiviral activities, using site-directed sequence- and structure-guided mutagenesis together with cell-based, biochemical, and HIV-1 infectivity assays.

Results

We have constructed a homology model of A3H HapII, which is similar to the known structures of other A3 proteins. The model revealed a large cluster of basic residues (not present in A3A or A3C) that are likely to be involved in nucleic acid binding. Indeed, RNase A pretreatment of 293T cell lysates expressing A3H was shown to be required for detection of deaminase activity, indicating that interaction with cellular RNAs inhibits A3H catalytic function. Similar observations have been made with A3G. Analysis of A3H deaminase substrate specificity demonstrated that a 5′ T adjacent to the catalytic C is preferred. Changing the putative nucleic acid binding residues identified by the model resulted in reduction or abrogation of enzymatic activity, while substituting Z3-specific residues in A3H to the corresponding residues in other A3 proteins did not affect enzyme function. As shown for A3G and A3F, some A3H mutants were defective in catalysis, but retained antiviral activity against HIV-1vif (−) virions. Furthermore, endogenous reverse transcription assays demonstrated that the E56A catalytic mutant inhibits HIV-1 DNA synthesis, although not as efficiently as wild type.

Conclusions

The molecular and biological activities of A3H are more similar to those of the double-domain A3 proteins than to those of A3A or A3C. Importantly, A3H appears to use both deaminase-dependent and -independent mechanisms to target reverse transcription and restrict HIV-1 replication.

【 授权许可】

   
2015 Mitra et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 3.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]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, 418:646-50.
• [2]Lecossier D, Bouchonnet F, Clavel F, Hance AJ: Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science 2003, 300:1112.
• [3]Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L: The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 2003, 424:94-8.
• [4]Suspène R, Sommer P, Henry M, Ferris S, Guétard D, Pochet S, et al.: APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase. Nucleic Acids Res 2004, 32:2421-9.
• [5]Yu Q, König R, Pillai S, Chiles K, Kearney M, Palmer S, et al.: Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol 2004, 11:435-42.
• [6]Harris RS, Liddament MT: Retroviral restriction by APOBEC proteins. Nat Rev Immunol 2004, 4:868-77.
• [7]Chiu YL, Greene WC: The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annu Rev Immunol 2008, 26:317-53.
• [8]Goila-Gaur R, Strebel K: HIV-1 Vif, APOBEC, and intrinsic immunity. Retrovirology 2008, 5:51.
• [9]Malim MH: APOBEC proteins and intrinsic resistance to HIV-1 infection. Philos Trans R Soc Lond B Biol Sci 2009, 364:675-87.
• [10]Imahashi M, Nakashima M, Iwatani Y: Antiviral mechanism and biochemical basis of the human APOBEC3 family. Front Microbiol 2012, 3:250.
• [11]Duggal NK, Fu W, Akey JM, Emerman M: Identification and antiviral activity of common polymorphisms in the APOBEC3 locus in human populations. Virology 2013, 443:329-37.
• [12]Desimmie BA, Delviks-Frankenberrry KA, Burdick RC, Qi D, Izumi T, Pathak VK: Multiple APOBEC3 restriction factors for HIV-1 and one Vif to rule them all. J Mol Biol 2014, 426:1220-45.
• [13]Feng Y, Baig TT, Love RP, Chelico L: Suppression of APOBEC3-mediated restriction of HIV-1 by Vif. Front Microbiol 2014, 5:450.
• [14]Sasada A, Takaori-Kondo A, Shirakawa K, Kobayashi M, Abudu A, Hishizawa M, et al.: APOBEC3G targets human T-cell leukemia virus type 1. Retrovirology 2005, 2:32.
• [15]Ooms M, Krikoni A, Kress AK, Simon V, Münk C: APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-lymphotropic virus type 1. J Virol 2012, 86:6097-108.
• [16]Turelli P, Mangeat B, Jost S, Vianin S, Trono D: Inhibition of hepatitis B virus replication by APOBEC3G. Science 2004, 303:1829.
• [17]Köck J, Blum HE: Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H. J Gen Virol 2008, 89:1184-91.
• [18]Koito A, Ikeda T: Intrinsic immunity against retrotransposons by APOBEC cytidine deaminases. Front Microbiol 2013, 4:28.
• [19]Jarmuz A, Chester A, Bayliss J, Gisbourne J, Dunham I, Scott J, et al.: An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22. Genomics 2002, 79:285-96.
• [20]Holmes RK, Malim MH, Bishop KN: APOBEC-mediated viral restriction: not simply editing? Trends Biochem Sci 2007, 32:118-28.
• [21]Bransteitter R, Prochnow C, Chen XS: The current structural and functional understanding of APOBEC deaminases. Cell Mol Life Sci 2009, 66:3137-47.
• [22]Betts L, Xiang S, Short SA, Wolfenden R, Carter CW Jr: Cytidine deaminase. The 2.3 Å crystal structure of an enzyme: transition-state analog complex. J Mol Biol 1994, 235:635-56.
• [23]LaRue RS, Jónsson SR, Silverstein KAT, Lajoie M, Bertrand D, El-Mabrouk N, et al.: The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals. BMC Mol Biol 2008, 9:104.
• [24]LaRue RS, Andrésdóttir V, Blanchard Y, Conticello SG, Derse D, Emerman M, et al.: Guidelines for naming nonprimate APOBEC3 genes and proteins. J Virol 2009, 83:494-7.
• [25]OhAinle M, Kerns JA, Malik HS, Emerman M: Adaptive evolution and antiviral activity of the conserved mammalian cytidine deaminase APOBEC3H. J Virol 2006, 80:3853-62.
• [26]OhAinle M, Kerns JA, Li MMH, Malik HS, Emerman M: Antiretroelement activity of APOBEC3H was lost twice in recent human evolution. Cell Host Microbe 2008, 4:249-59.
• [27]Harari A, Ooms M, Mulder LCF, Simon V: Polymorphisms and splice variants influence the antiretroviral activity of human APOBEC3H. J Virol 2009, 83:295-303.
• [28]Ooms M, Majdak S, Seibert CW, Harari A, Simon V: The localization of APOBEC3H variants in HIV-1 virions determines their antiviral activity. J Virol 2010, 84:7961-9.
• [29]Wang X, Abudu A, SungMo S, Dang Y, Venta PJ, Zheng Y-H: Analysis of human APOBEC3H haplotypes and anti-human immunodeficiency virus type 1 activity. J Virol 2011, 85:3142-52.
• [30]Li MMH, Wu LI, Emerman M: The range of human APOBEC3H sensitivity to lentiviral Vif proteins. J Virol 2010, 84:88-95.
• [31]Zhen A, Wang T, Zhao K, Xiong Y, Yu X-F: A single amino acid difference in human APOBEC3H variants determines HIV-1 Vif sensitivity. J Virol 2010, 84:1902-11.
• [32]Ooms M, Brayton B, Letko M, Maio SM, Pilcher CD, Hecht FM, et al.: HIV-1 Vif adaptation to human APOBEC3H haplotypes. Cell Host Microbe 2013, 14:411-21.
• [33]Binka M, Ooms M, Steward M, Simon V: The activity spectrum of Vif from multiple HIV-1 subtypes against APOBEC3G, APOBEC3F, and APOBEC3H. J Virol 2012, 86:49-59.
• [34]Ooms M, Letko M, Binka M, Simon V: The resistance of human APOBEC3H to HIV-1 NL4-3 molecular clone is determined by a single amino acid in Vif. PLoS One 2013, 8:e57744.
• [35]Chen H, Lilley CE, Yu Q, Lee DV, Chou J, Narvaiza I, et al.: APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons. Curr Biol 2006, 16:480-5.
• [36]Aguiar RS, Lovsin N, Tanuri A, Peterlin BM: Vpr.A3A chimera inhibits HIV replication. J Biol Chem 2008, 283:2518-25.
• [37]Stenglein MD, Burns MB, Li M, Lengyel J, Harris RS: APOBEC3 proteins mediate the clearance of foreign DNA from human cells. Nat Struct Mol Biol 2010, 17:222-9.
• [38]Bulliard Y, Narvaiza I, Bertero A, Peddi S, Röhrig UF, Ortiz M, et al.: Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction activities. J Virol 2011, 85:1765-76.
• [39]Love RP, Xu H, Chelico L: Biochemical analysis of hypermutation by the deoxycytidine deaminase APOBEC3A. J Biol Chem 2012, 287:30812-22.
• [40]Shinohara M, Io K, Shindo K, Matsui M, Sakamoto T, Tada K, et al.: APOBEC3B can impair genomic stability by inducing base substitutions in genomic DNA in human cells. Sci Rep 2012, 2:806.
• [41]Byeon I-JL, Ahn J, Mitra M, Byeon C-H, Hercík K, Hritz J, et al.: NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity. Nat Commun 2013, 4:1890.
• [42]Mitra M, Hercík K, Byeon I-JL, Ahn J, Hill S, Hinchee-Rodriguez K, et al.: Structural determinants of human APOBEC3A enzymatic and nucleic acid binding properties. Nucleic Acids Res 2014, 42:1095-110.
• [43]Holden LG, Prochnow C, Chang YP, Bransteitter R, Chelico L, Sen U, et al.: Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications. Nature 2008, 456:121-4.
• [44]Carpenter MA, Rajagurubandara E, Wijesinghe P, Bhagwat AS: Determinants of sequence-specificity within human AID and APOBEC3G. DNA Repair 2010, 9:579-87.
• [45]Kohli RM, Maul RW, Guminski AF, McClure RL, Gajula KS, Saribasak H, et al.: Local sequence targeting in the AID/APOBEC family differentially impacts retroviral restriction and antibody diversification. J Biol Chem 2010, 285:40956-64.
• [46]Rathore A, Carpenter MA, Demir Ö, Ikeda T, Li M, Shaban NM, et al.: The local dinucleotide preference of APOBEC3G can be altered from 5'-CC to 5'-TC by a single amino acid substitution. J Mol Biol 2013, 425:4442-54.
• [47]Aydin H, Taylor MW, Lee JE: Structure-guided analysis of the human APOBEC3-HIV restrictome. Structure 2014, 22:668-84.
• [48]Kim E-Y, Lorenzo-Redondo R, Little SJ, Chung Y-S, Phalora PK, Maljkovic Berry I, et al.: Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection. PLoS Pathog 2014, 10:e1004281.
• [49]Kitamura S, Ode H, Nakashima M, Imahashi M, Naganawa Y, Kurosawa T, et al.: The APOBEC3C crystal structure and the interface for HIV-1 Vif binding. Nat Struct Mol Biol 2012, 19:1005-10.
• [50]Chen KM, Harjes E, Gross PJ, Fahmy A, Lu Y, Shindo K, et al.: Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G. Nature 2008, 452:116-9.
• [51]Furukawa A, Nagata T, Matsugami A, Habu Y, Sugiyama R, Hayashi F, et al.: Structure, interaction and real-time monitoring of the enzymatic reaction of wild-type APOBEC3G. EMBO J 2009, 28:440-51.
• [52]Harjes E, Gross PJ, Chen K-M, Lu Y, Shindo K, Nowarski R, et al.: An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model. J Mol Biol 2009, 389:819-32.
• [53]Shandilya SMD, Nalam MNL, Nalivaika EA, Gross PJ, Valesano JC, Shindo K, et al.: Crystal structure of the APOBEC3G catalytic domain reveals potential oligomerization interfaces. Structure 2010, 18:28-38.
• [54]Bohn M-F, Shandilya SMD, Albin JS, Kouno T, Anderson BD, McDougle RM, et al.: Crystal structure of the DNA cytosine deaminase APOBEC3F: the catalytically active and HIV-1 Vif-binding domain. Structure 2013, 21:1042-50.
• [55]Siu KK, Sultana A, Azimi FC, Lee JE: Structural determinants of HIV-1 Vif susceptibility and DNA binding in APOBEC3F. Nat Commun 2013, 4:2593.
• [56]Šali A, Blundell TL: Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 1993, 234:779-815.
• [57]Zhen A, Du J, Zhou X, Xiong Y, Yu X-F: Reduced APOBEC3H variant anti-viral activities are associated with altered RNA binding activities. PLoS One 2012, 7:e38771.
• [58]Haché G, Liddament MT, Harris RS: The retroviral hypermutation specificity of APOBEC3F and APOBEC3G is governed by the C-terminal DNA cytosine deaminase domain. J Biol Chem 2005, 280:10920-4.
• [59]Langlois M-A, Beale RCL, Conticello SG, Neuberger MS: 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 2005, 33:1913-23.
• [60]Navarro F, Bollman B, Chen H, König R, Yu Q, Chiles K, et al.: Complementary function of the two catalytic domains of APOBEC3G. Virology 2005, 333:374-86.
• [61]Iwatani Y, Takeuchi H, Strebel K, Levin JG: Biochemical activities of highly purified, catalytically active human APOBEC3G: correlation with antiviral effect. J Virol 2006, 80:5992-6002.
• [62]Hultquist JF, Lengyel JA, Refsland EW, LaRue RS, Lackey L, Brown WL, et al.: Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1. J Virol 2011, 85:11220-34.
• [63]McDougall WM, Smith HC: Direct evidence that RNA inhibits APOBEC3G ssDNA cytidine deaminase activity. Biochem Biophys Res Commun 2011, 412:612-7.
• [64]Huthoff H, Autore F, Gallois-Montbrun S, Fraternali F, Malim MH: RNA-dependent oligomerization of APOBEC3G is required for restriction of HIV-1. PLoS Pathog 2009, 5:e1000330.
• [65]Newman ENC, Holmes RK, Craig HM, Klein KC, Lingappa JR, Malim MH, et al.: Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity. Curr Biol 2005, 15:166-70.
• [66]Bishop KN, Holmes RK, Malim MH: Antiviral potency of APOBEC proteins does not correlate with cytidine deamination. J Virol 2006, 80:8450-8.
• [67]Guo F, Cen S, Niu M, Saadatmand J, Kleiman L: Inhibition of tRNA3Lys-primed reverse transcription by human APOBEC3G during human immunodeficiency virus type 1 replication. J Virol 2006, 80:11710-22.
• [68]Holmes RK, Koning FA, Bishop KN, Malim MH: APOBEC3F can inhibit the accumulation of HIV-1 reverse transcription products in the absence of hypermutation. Comparisons with APOBEC3G. J Biol Chem 2007, 282:2587-95.
• [69]Iwatani Y, Chan DSB, Wang F, Maynard KS, Sugiura W, Gronenborn AM, et al.: Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G. Nucleic Acids Res 2007, 35:7096-108.
• [70]Li X-Y, Guo F, Zhang L, Kleiman L, Cen S: APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. J Biol Chem 2007, 282:32065-74.
• [71]Luo K, Wang T, Liu B, Tian C, Xiao Z, Kappes J, et al.: Cytidine deaminases APOBEC3G and APOBEC3F interact with human immunodeficiency virus type 1 integrase and inhibit proviral DNA formation. J Virol 2007, 81:7238-48.
• [72]Mbisa JL, Barr R, Thomas JA, Vandegraaff N, Dorweiler IJ, Svarovskaia ES, et al.: Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration. J Virol 2007, 81:7099-110.
• [73]Bishop KN, Verma M, Kim E-Y, Wolinsky SM, Malim MH: APOBEC3G inhibits elongation of HIV-1 reverse transcripts. PLoS Pathog 2008, 4:e1000231.
• [74]Levin JG, Mitra M, Mascarenhas A, Musier-Forsyth K: Role of HIV-1 nucleocapsid protein in HIV-1 reverse transcription. RNA Biol 2010, 7:754-74.
• [75]Wang X, Ao Z, Chen L, Kobinger G, Peng J, Yao X: The cellular antiviral protein APOBEC3G interacts with HIV-1 reverse transcriptase and inhibits its function during viral replication. J Virol 2012, 86:3777-86.
• [76]Adolph MB, Webb J, Chelico L: Retroviral restriction factor APOBEC3G delays the initiation of DNA synthesis by HIV-1 reverse transcriptase. PLoS One 2013, 8:e64196.
• [77]Bélanger K, Savoie M, Rosales Gerpe MC, Couture J-F, Langlois M-A: Binding of RNA by APOBEC3G controls deamination-independent restriction of retroviruses. Nucleic Acids Res 2013, 41:7438-52.
• [78]Gillick K, Pollpeter D, Phalora P, Kim E-Y, Wolinsky SM, Malim MH: Suppression of HIV-1 infection by APOBEC3 proteins in primary human CD4+ T cells is associated with inhibition of processive reverse transcription as well as excessive cytidine deamination. J Virol 2013, 87:1508-17.
• [79]Chaurasiya KR, McCauley MJ, Wang W, Qualley DF, Wu T, Kitamura S, et al.: Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein. Nat Chem 2014, 6:28-33.
• [80]Dang Y, Siew LM, Wang X, Han Y, Lampen R, Zheng YH: Human cytidine deaminase APOBEC3H restricts HIV-1 replication. J Biol Chem 2008, 283:11606-14.
• [81]Shandilya SMD, Bohn M-F, Schiffer CA: A computational analysis of the structural determinants of APOBEC3's catalytic activity and vulnerability to HIV-1 Vif. Virology 2014, 471–473:105-16.
• [82]Chiu Y-L, Witkowska HE, Hall SC, Santiago M, Soros VB, Esnault C, et al.: High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition. Proc Natl Acad Sci U S A 2006, 103:15588-93.
• [83]Kozak SL, Marin M, Rose KM, Bystrom C, Kabat D: The anti-HIV-1 editing enzyme APOBEC3G binds HIV-1 RNA and messenger RNAs that shuttle between polysomes and stress granules. J Biol Chem 2006, 281:29105-19.
• [84]Gallois-Montbrun S, Kramer B, Swanson CM, Byers H, Lynham S, Ward M, et al.: Antiviral protein APOBEC3G localizes to ribonucleoprotein complexes found in P bodies and stress granules. J Virol 2007, 81:2165-78.
• [85]Chelico L, Sacho EJ, Erie DA, Goodman MF: A model for oligomeric regulation of APOBEC3G cytosine deaminase-dependent restriction of HIV. J Biol Chem 2008, 283:13780-91.
• [86]Gallois-Montbrun S, Holmes RK, Swanson CM, Fernández-Ocaña M, Byers HL, Ward MA, et al.: Comparison of cellular ribonucleoprotein complexes associated with the APOBEC3F and APOBEC3G antiviral proteins. J Virol 2008, 82:5636-42.
• [87]Friew YN, Boyko V, Hu W-S, Pathak VK: Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G multimerization is dependent on its association with RNA. Retrovirology 2009, 6:56.
• [88]Salter JD, Krucinska J, Raina J, Smith HC, Wedekind JE: A hydrodynamic analysis of APOBEC3G reveals a monomer-dimer-tetramer self-association that has implications for anti-HIV function. Biochemistry 2009, 48:10685-7.
• [89]Chelico L, Prochnow C, Erie DA, Chen XS, Goodman MF: Structural model for deoxycytidine deamination mechanisms of the HIV-1 inactivation enzyme APOBEC3G. J Biol Chem 2010, 285:16195-205.
• [90]McDougall WM, Okany C, Smith HC: Deaminase activity on single-stranded DNA (ssDNA) occurs in vitro when APOBEC3G cytidine deaminase forms homotetramers and higher-order complexes. J Biol Chem 2011, 286:30655-61.
• [91]Shlyakhtenko LS, Lushnikov AY, Li M, Lackey L, Harris RS, Lyubchenko YL: Atomic force microscopy studies provide direct evidence for dimerization of the HIV restriction factor APOBEC3G. J Biol Chem 2011, 286:3387-95.
• [92]Li J, Chen Y, Li M, Carpenter MA, McDougle RM, Luengas EM, et al.: APOBEC3 multimerization correlates with HIV-1 packaging and restriction activity in living cells. J Mol Biol 2014, 426:1296-307.
• [93]Baig TT, Feng Y, Chelico L: Determinants of efficient degradation of APOBEC3 restriction factors by HIV-1 Vif. J Virol 2014, 88:14380-95.
• [94]Tan L, Sarkis PTN, Wang T, Tian C, Yu X-F: Sole copy of Z2-type human cytidine deaminase APOBEC3H has inhibitory activity against retrotransposons and HIV-1. FASEB J 2009, 23:279-87.
• [95]Goila-Gaur R, Khan MA, Miyagi E, Kao S, Strebel K: Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity. Retrovirology 2007, 4:61.
• [96]Song C, Sutton L, Johnson ME, D'Aquila RT, Donahue JP: Signals in APOBEC3F N-terminal and C-terminal deaminase domains each contribute to encapsidation in HIV-1 virions and are both required for HIV-1 restriction. J Biol Chem 2012, 287:16965-74.
• [97]Bennett RP, Diner E, Sowden MP, Lees JA, Wedekind JE, Smith HC: APOBEC-1 and AID are nucleo-cytoplasmic trafficking proteins but APOBEC3G cannot traffic. Biochem Biophys Res Commun 2006, 350:214-9.
• [98]Wichroski MJ, Robb GB, Rana TM: Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies. PLoS Pathog 2006, 2:e41.
• [99]Bennett RP, Presnyak V, Wedekind JE, Smith HC: Nuclear exclusion of the HIV-1 host defense factor APOBEC3G requires a novel cytoplasmic retention signal and is not dependent on RNA binding. J Biol Chem 2008, 283:7320-7.
• [100]Li MMH, Emerman M: Polymorphism in human APOBEC3H affects a phenotype dominant for subcellular localization and antiviral activity. J Virol 2011, 85:8197-207.
• [101]Chelico L, Pham P, Calabrese P, Goodman MF: APOBEC3G DNA deaminase acts processively 3' → 5' on single-stranded DNA. Nat Struct Mol Biol 2006, 13:392-9.
• [102]Platt EJ, Wehrly K, Kuhmann SE, Chesebro B, Kabat D: Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. J Virol 1998, 72:2855-64.
• [103]Derdeyn CA, Decker JM, Sfakianos JN, Wu X, O'Brien WA, Ratner L, et al.: 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 2000, 74:8358-67.
• [104]Wei X, Decker JM, Liu H, Zhang Z, Arani RB, Kilby JM, et al.: Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 2002, 46:1896-905.
• [105]Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA: Development and testing of a general amber force field. J Comput Chem 2004, 25:1157-74.
• [106]Dolinsky TJ, Czodrowski P, Li H, Nielsen JE, Jensen JH, Klebe G, et al.: PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Res 2007, 35:W522-5.
• [107]Koradi R, Billeter M, Wüthrich K: MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph 1996, 14:51-5.
• [108]Green TD, Newton BR, Rota PA, Xu Y, Robinson HL, Ross TM: C3d enhancement of neutralizing antibodies to measles hemagglutinin. Vaccine 2001, 20:242-8.
• [109]Thomas JA, Shatzer TL, Gorelick RJ: Blocking premature reverse transcription fails to rescue the HIV-1 nucleocapsid-mutant replication defect. Retrovirology 2011, 8:46.
• [110]Ott DE, Coren LV, Johnson DG, Sowder RC II, Arthur LO, Henderson LE: Analysis and localization of cyclophilin A found in the virions of human immunodeficiency virus type 1 MN strain. AIDS Res Hum Retroviruses 1995, 11:1003-6.
• [111]Thomas JA, Gagliardi TD, Alvord WG, Lubomirski M, Bosche WJ, Gorelick RJ: Human immunodeficiency virus type 1 nucleocapsid zinc-finger mutations cause defects in reverse transcription and integration. Virology 2006, 353:41-51.