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Homologous Testify to the Common Ancestry of , Caulimoviruses, Pseudoviruses, and Metaviruses Mart Krupovic, Eugene Koonin

To cite this version:

Mart Krupovic, Eugene Koonin. Homologous Capsid Proteins Testify to the Common Ancestry of Retroviruses, Caulimoviruses, Pseudoviruses, and Metaviruses. Journal of , American Society for , 2017, 91 (12), pp.e00210-17. ￿10.1128/JVI.00210-17￿. ￿pasteur-01977363￿

HAL Id: pasteur-01977363 https://hal-pasteur.archives-ouvertes.fr/pasteur-01977363 Submitted on 10 Jan 2019

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Distributed under a Creative Commons Attribution - NonCommercial - ShareAlike| 4.0 International License JVI Accepted Manuscript Posted Online 29 March 2017 J. Virol. doi:10.1128/JVI.00210-17 Copyright © 2017 American Society for Microbiology. All Rights Reserved.

1 Homologous capsid proteins testify to the common ancestry of retroviruses, caulimoviruses, 2 pseudoviruses and metaviruses 3

4 Mart Krupovica* and Eugene V. Kooninb

5 6 a – Unité Biologie Moléculaire du Gène chez les Extrêmophiles, Institut Pasteur, 25 rue du Docteur Roux,

7 75015 Downloaded from 8 b – National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, 9 USA 10 11 * – Correspondence 12 E-mail: [email protected] 13

14 http://jvi.asm.org/

15 Text

16 Reverse-transcribing are classified into 5 different families, Retroviridae, ,

17 , and (1). Retroviruses, hepadnaviruses and caulimoviruses

18 are full-fledged viruses, whereas metaviruses and pseudoviruses are more often referred to as on January 30, 2019 by guest 19 . Nevertheless, similar to other reverse-transcribing viruses, certain members of the

20 families Metaviridae and Pseudoviridae form icosahedral or irregularly-shaped particles that play

21 important roles in their infection cycles (2, 3). Phylogenetic analyses reveal monophyly of the reverse

22 transcriptases (RT) of all these viruses, to the exclusion of the RTs of other retroelements (1, 4). By

23 contrast, the evolutionary relationships between the capsid proteins (CP) of these viruses remain

24 obscure.

25

26 Evolutionary connections between viruses that have diverged in a distant past are often difficult to trace

27 due to high mutation and recombination rates in the viral , which abrogate their taxonomic

28 classification, especially at the level of higher taxa. However, it has been argued that comparison of

29 sequences and structures of the major virion proteins provides a deeper reach into the evolutionary

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30 history of the virosphere (5-8). High-resolution CP structures are available for several retroviruses and

31 hepadnaviruses. Members of the Retroviridae encode their CP as part of a larger polyprotein precursor

32 known as Gag, which is proteolytically processed by the -encoded protease to release several major

33 proteins, three of which, namely matrix, capsid (CA), nucleocapsid (NC), are conserved in all retroviruses

34 (9). The CA is composed of two α-helical domains, the N-terminal domain (NTD) and the C- Downloaded from

35 terminal domain (CTD) (10, 11). The CP of hepadnaviruses also adopts an α-helical fold, but does not

36 bear recognizable similarity to retroviral CA (12). By contrast, members of the family Metaviridae,

37 including Ty3/Gypsy retrotransposons, encode a Gag polyprotein, which contains the CA and NC domains

38 related to those of retroviruses (13, 14). Additionally, the Zn-binding module, known as ‘Zn-knuckle’, that http://jvi.asm.org/

39 is found in many and metavirus NC domains is also present in the CPs of caulimoviruses and

40 members of the family Pseudoviridae, such as Ty1/Copia retrotransposons (15). However, the CPs from

41 the latter two groups of viruses are generally considered to be unrelated to the CA of retroviruses or

42 metaviruses (1, 16), suggesting that different groups of reverse-transcribing viruses could have evolved on January 30, 2019 by guest 43 from non-viral retroelements via acquisition of capsid-encoding genes from different sources. As a case

44 in point, envelope proteins responsible for host recognition and membrane fusion have been recruited

45 by reverse-transcribing viruses on several independent occasions (1, 17).

46

47 To investigate the provenance of the pseudovirus and CPs, we performed sensitive profile-

48 profile searches using HHpred (18) seeded with sequences of CPs of pseudoviruses, caulimoviruses and

49 metaviruses. In all cases, we obtained highly significant matches (>98% HHpred probability) to the Gag of

50 retroviruses. The region of similarity encompasses the end of the CA-NTD and extends throughout the

51 CA-CTD and NC (data not shown). To validate these matches, we aligned the retroviral CA-NC sequences

52 to the corresponding protein sequences from the three other families of reverse-transcribing viruses.

53 Inspection of the alignment showed that the sequence conservation among the aligned proteins

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54 encompasses not only CA-CTD and NC domains but also CA-NTD, except for two short α-helixes (α5 and

55 α6) that have no equivalents in CPs of viruses other than retroviruses (Figures 1 and 2). Importantly, non-

56 polar residues, which stabilize the hydrophobic core of the α-helical bundles of both CA-NTD and CA-CTD

57 (10, 19), are conserved in all CP/CA proteins. Thus, patterns of sequence and secondary structure

58 conservation strongly support the homology of the CA/CP-NC module of all reverse-transcribing viruses, Downloaded from

59 except for hepadnaviruses. This result, combined with the monophyly of viral RTs (4), strongly suggests

60 that retroviruses, caulimoviruses, pseudoviruses and metaviruses evolved from a common viral ancestor,

61 rather than from distinct capsid-less retrotransposons. Such an ancestral virus encoding the CA/CP-NC,

62 protease (14) and the RT, including the RNase H domain (20), is likely to have existed prior to the http://jvi.asm.org/

63 divergence of plants and opisthokonts (fungi and animals) ~1.6 billion years ago (21). Furthermore, given

64 that, in the RT phylogeny, hepadnaviruses cluster with pseudoviruses (1, 4), it appears most likely that

65 the conserved CP/CA was acquired by the common ancestor of all reverse-transcribing viruses, followed

66 by replacement with an unrelated protein in hepadnaviruses. Finally, our results seem to justify the on January 30, 2019 by guest 67 creation of a single, high-order viral taxon unifying all families of reverse-transcribing viruses (or

68 alternatively, four families, excluding hepadnaviruses), consistent with previous suggestions based on

69 the shared mechanisms of replication employed by these viruses (22).

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70 References 71 1. Koonin, E. V., V. V. Dolja, and M. Krupovic. 2015. Origins and evolution of viruses of : 72 The ultimate modularity. Virology 479-480:2-25. 73 2. King, A. M. Q., M. J. Adams, E. B. Carstens, and E. J. Lefkowitz. 2011. Virus Taxonomy. Ninth 74 Report of the International Committee on Taxonomy of Viruses. Elsevier Academic, London. 75 3. Palmer, K. J., W. Tichelaar, N. Myers, N. R. Burns, S. J. Butcher, A. J. Kingsman, S. D. Fuller, and 76 H. R. Saibil. 1997. Cryo-electron microscopy structure of yeast Ty virus-like 77 particles. J Virol 71:6863-8. 78 4. Gladyshev, E. A., and I. R. Arkhipova. 2011. A widespread class of -related Downloaded from 79 cellular genes. Proc Natl Acad Sci U S A 108:20311-6. 80 5. Krupovic, M., and D. H. Bamford. 2010. Order to the viral universe. J Virol 84:12476-9. 81 6. Sinclair, R. M., J. J. Ravantti, and D. H. Bamford. 2017. Nucleic and amino acid sequences 82 support structure-based viral classification. J Virol. 83 7. Krupovic, M., and E. V. Koonin. 2017. Multiple origins of viral capsid proteins from cellular 84 ancestors. Proc Natl Acad Sci U S A 114:E2401-E2410. 85 8. Abrescia, N. G., D. H. Bamford, J. M. Grimes, and D. I. Stuart. 2012. Structure unifies the viral 86 universe. Annu Rev Biochem 81:795-822. http://jvi.asm.org/ 87 9. Mattei, S., F. K. Schur, and J. A. Briggs. 2016. Retrovirus maturation-an extraordinary structural 88 transformation. Curr Opin Virol 18:27-35. 89 10. Ganser-Pornillos, B. K., A. Cheng, and M. Yeager. 2007. Structure of full-length HIV-1 CA: a 90 model for the mature capsid lattice. Cell 131:70-9. 91 11. Ganser-Pornillos, B. K., M. Yeager, and W. I. Sundquist. 2008. The structural biology of HIV 92 assembly. Curr Opin Struct Biol 18:203-17. 93 12. Steven, A. C., J. F. Conway, N. Cheng, N. R. Watts, D. M. Belnap, A. Harris, S. J. Stahl, and P. T. 94 Wingfield. 2005. Structure, assembly, and antigenicity of virus capsid proteins. Adv 95 Virus Res 64:125-64. on January 30, 2019 by guest 96 13. Larsen, L. S., M. Zhang, N. Beliakova-Bethell, V. Bilanchone, A. Lamsa, K. Nagashima, R. Najdi, 97 K. Kosaka, V. Kovacevic, J. Cheng, P. Baldi, G. W. Hatfield, and S. Sandmeyer. 2007. Ty3 capsid 98 mutations reveal early and late functions of the amino-terminal domain. J Virol 81:6957-72. 99 14. Llorens, C., M. A. Fares, and A. Moya. 2008. Relationships of gag-pol diversity between 100 Ty3/Gypsy and Retroviridae LTR retroelements and the three kings hypothesis. BMC Evol Biol 101 8:276. 102 15. Covey, S. N. 1986. Amino acid sequence homology in gag region of reverse transcribing elements 103 and the coat protein gene of cauliflower . Nucleic Acids Res 14:623-33. 104 16. Pachulska-Wieczorek, K., S. F. Le Grice, and K. J. Purzycka. 2016. Determinants of Genomic RNA 105 Encapsidation in the Saccharomyces cerevisiae Long Terminal Repeat Retrotransposons Ty1 and 106 Ty3. Viruses 8:E193. 107 17. Malik, H. S., S. Henikoff, and T. H. Eickbush. 2000. Poised for contagion: evolutionary origins of 108 the infectious abilities of invertebrate retroviruses. Genome Res 10:1307-18. 109 18. Söding, J. 2005. Protein homology detection by HMM-HMM comparison. Bioinformatics 21:951- 110 60. 111 19. Ball, N. J., G. Nicastro, M. Dutta, D. J. Pollard, D. C. Goldstone, M. Sanz-Ramos, A. Ramos, E. 112 Mullers, K. Stirnnagel, N. Stanke, D. Lindemann, J. P. Stoye, W. R. Taylor, P. B. Rosenthal, and I. 113 A. Taylor. 2016. Structure of a spumaretrovirus Gag central domain reveals an ancient retroviral 114 capsid. PLoS Pathog 12:e1005981. 115 20. Malik, H. S., and T. H. Eickbush. 2001. Phylogenetic analysis of ribonuclease H domains suggests 116 a late, chimeric origin of LTR retrotransposable elements and retroviruses. Genome Res 11:1187- 117 97.

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118 21. Hedges, S. B., J. E. Blair, M. L. Venturi, and J. L. Shoe. 2004. A molecular timescale of 119 evolution and the rise of complex multicellular life. BMC Evol Biol 4:2. 120 22. Hull, R. 2001. Classifying reverse transcribing elements: a proposal and a challenge to the ICTV. 121 International Committee on Taxonomy of Viruses. Arch Virol 146:2255-61. 122 23. Llorens, C., R. Futami, D. Bezemer, and A. Moya. 2008. The Gypsy Database (GyDB) of mobile 123 genetic elements. Nucleic Acids Res 36:D38-46. 124 24. Pei, J., and N. V. Grishin. 2014. PROMALS3D: multiple protein sequence alignment enhanced 125 with evolutionary and three-dimensional structural information. Methods Mol Biol 1079:263-71.

126 Downloaded from 127 http://jvi.asm.org/ on January 30, 2019 by guest

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128 Figure legend

129 Figure 1. Multiple sequence alignment of CA/CP proteins of reverse-transcribing viruses belonging to

130 families Retroviridae, Metaviridae, Pseudoviridae and Caulimoviridae. Representative sequences from all

131 four virus groups were downloaded from the Gypsy Database (23), supplemented with sequences of

132 retroviral CA proteins for which X-ray structures are available and were aligned using PROMALS3D (24). Downloaded from

133 Secondary structure elements above the alignment are indicated for the CA (PDB:

134 5A9E), which was retrieved as the best hit to CP proteins of metaviruses, pseudoviruses and

135 caulimoviruses in HHpred search (data not shown). Red and blue asterisks indicate the conserved

136 residues in the single or tandem Zn-knuckle motifs of the nucleocapsid (NC) domain. Abbreviations: HIV- http://jvi.asm.org/

137 1, human immunodeficiency virus 1; BLV, bovine virus; JSRV, Jaagsiekte sheep retrovirus; LPDV,

138 lymphoproliferative disease virus; MMTV, mouse mammary tumor virus; PyERV, Python molurus

139 ; EIAV, virus; BSGFV, banana streak goldfinger virus;

140 BSOLV, banana streak OL (badna)virus; CaMV, ; CERV, carnation etched ring on January 30, 2019 by guest 141 virus; DBV, dasheen bacilliform virus; DrMV, Dracaena mottle virus; MiMV, Mirabilis mosaic virus; TaBV,

142 taro bacilliform virus.

143

144 Figure 2. Conservation of the amino acid residues contributing to the stabilization of the hydrophobic

145 core of the α-helical bundles of CA-NTD and CA-CTD. Sequence conservation derived from the alignment

146 shown in Figure 1 was mapped onto the CA structure of Rous sarcoma virus (PDB: 5A9E). The least

147 conserved regions are colored red, whereas those most conserved are in blue.

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CA-NTD α1 α2 α3 α4 α5

HIV-1:4d1k 145 QAISPRTLNAWVKVVEEKAFSPEVIP---MFSALSEGA------TP------QDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQ----MREPRGSD 234 RSV:5a9e 1 TPLEPKLITRLADTVRTKG-LRSPITMAEVEALMSSPL------LP------HDVTNLMRVILG-PAPYALWMDAWGVQLQTVIAAATRDPRHPANGQGRGERTNLDRLK 95 BLV:4ph0 9 RAWALRELQDIKKEIENKAPGSQVWIQTLRLAILQADP------TP------ADLEQLCQYIAS-PVDQTAHMTSLTAAIAAAEAANTLQGF------N 87 JSRV 1 -SLPFKQLKELKIACSQYG-PTAPFTIAMIESLGTQAL------PP------NDWKQTARACLS-GGDYLLWKSEFFEQCARIADVNRQQGIQ------TSYE 81 LPDV 1 TPLDPKMVKQLKEAIQEEG-TTGPLASVLLDQVHQIAL------TP------SDLRQLARIVLS-PVMAALWKSEWTERLQARVTTATHDRRDPLH------GVTVAV 87 MMTV 1 -PLPLKTLKELQSAVRTMG-PSAPYTLQVVDMVASQWL------TP------SDWHQTARATLS-PGDYVLWRTEYEEKSKEMVQKAAGKRKGK------VSLD 82

Retroviridae MPMV 1 NGFDFAVIKELKTAASQYG-ATAPYTLAIVESVADNWL------TP------TDWNTLVRAVLS-GGDHLLWKSEFFENCRDTAKRNQQAGNG------WDFD 82 PyERV 1 --IDYKQIKEIKSAVRDYG-LQSRYVMGLLTSLSTAAV------EMLL------ADWQSLFGMILT-PAQYVIWNSEYGKQAAVAINAGLPQNV------TAD 80 EIAV:2eia 1 ------PRG---YTTWVNTIQTNGLLNEASQNLFGILS------VDCT------SEEMNAFLDVVPGQAGQKQILLDAIDKIADDWDNRHPLPNAPLVAPP----QGPIPMTA 87 Amn-ni 1 RLPPPRHFS----GDPSA--CDGFLT---QCSLTFELQPSSFPSD------RAQIAYVITLLS-GKALSWATAVWKAKSPFCS------67 Beetle1 1 IKLDVPEFD----GNLNPDAYLEWVS---RCNRIF--ELKEYDD------SKSFKLAITKLK-GYASLWWENVALARERK------HKPKIK------70 Blastopia 11 VIIAAEKFEKVVSDCDGK--SIPIKK----WFEIFEKNAEAYELSE------KQKYVQARSKMI-GSAELFLESECVS------75 Cer4 1 ---TKYQFS----LE-EPDSFRRWWD---RHHLIFSEDAAELSE------RERTRLLLSCLE-EGTFRRFVDTQRNICDIYEV------65 DRM 1 LIGSIGEFA----PKAES--WSAYIE---RLEQFF--VANEISQ------EKQVATLLSVMG-ATTYGLLRNFVRLILWLFW------64 Hydra2-1 1 HFGNLSEFN----SN-ED--WDNYVE---RLDFFD--IANDIVNE------EQQRAILLSSCG-HATYKLFKSLVAPGKTSDR------64

Metaviridae Micropia 1 ------SYDVKLPKFNPDAACVEAAKWCSTTDIIL------TPLKGSEHPLKGSKLITALSNCME-GTASQWLTQISYQGM------68 Osvaldo 2 PSSSEQEYPKVAKHVREWNFRFDGTSKPLEF-LEQVE------WSADTYGLDL---DLIPRAMPELLK-GMALKWYVANNRHWR------74 Ty3-1 1 -IQPSLTFR----GRNDSHKLKNFIS---EIMLNM--SMISWPND------ASRIVYCRRHLL-NPAAQWANDFVQEQGILEI------66 Bel 4 --IKLPTFS----GNYED--WKHFSD---MFIGSIASNSSLTD------CQRFHYLKSYLA-GDALALVKHIPVTND------62 Pao 4 --LP--FFN----GNHQD--WLSFRA---AYHET---MNSFTK------TENINRLRRNLK-GRAKEAVDGLLITNA------57 Copia 9 YAIWKFRIR-ALLAEQDV--LKVVDG---LMPNEVDDSWKKAE------RCAKSTIIEYLS-DSFLNFATSDI------68 Fourf 4 WLTAMSCFH----AAEGK--PANLPP---EDEAKF--KAED------NLFRGAVISALD-TKFQKSYIILP------56 Downloaded from Oryco1-2 10 YQDWVLVMR-VNMQAQGL--WGAVE----PEGDDLVD-YRQD------RQALTAILRAVP-AEM------58 BSGFV 66 LPSANARQGSIFVMPYDFD--VKVFERWESSVLVHLADKNFDTP------EDKVIYIENLLG-ESEKKAFMTWRMKYLPEFEALKAAAL------G 145 Pseudoviridae BSOLV 68 LPPAQSRQGAMFVMPMDFD--IKVFERWESITLLHMTEKIFDNA------DDKMRYMENLLG-EDEKKHFIEWRMKYTAEYETMKAQAL------G 147 CaMV 1 -MLNIDCQTN---RRTLIDDWAAEIGLIVKTNREDYL------DP------ETILLLMEHKTS-GIAKELIRNTRWNRTTGD------65 CERV 1 -ILNLDCVNSPSDRKNKIDKWAAELGLVFLTNPEAYT------TAPNAA------RARLAYMEHKSL-GIVNRFIKSTQWTQMNGD------72 CSSV 71 LPSSQGTTGALFVMPKQMGLFHEVFSRWESITKNYVAAQGFTDP------TEKMEFMENLLG-ETEKLTWIQWRMNYEAEYQQLLTQAD------G 152 DBV 66 LPSAQQTTGAMFYMPLELDKFDEVFSRWESITKNITSQHSFISG------REKADFIENLLG-ETEKLTWIQWRTTFNAEFDSLIAAAD------G 147 DrMV 75 LPSAQQLRGALLVLPEDIGLYQDVISRWETITLNVLADKVFSDN------RSKLMYVENLLG-EDEKKAWIQWRMAFEQEYESLIAVAD------156 Caulimoviridae MiMV 1 -TINIDCIGDLDLRRKIIDKWINEIDLIVQTSPNDFT------TS------RSVLVLMEHRSD-GMIRNFIKKASWSSQMTGSQ------70 TaBV 64 LPPAYNQQGAILVLPDDIGLYEDTISRWESITLNMMNEKVWPSN------EAKAKYMENLLG-EMEKKTWIQWRTTYVSEYDALVQQSD------145 CA-NTD α6 α7 3/10-helix α8 α9

HIV-1:4d1k 235 DIAGTTSTLQEQIGWMTNN--PPIPVGEIYKRWIILGLNKIVRMYSP------TSILDI----RQGP--KEPFRDYVDRFYKTLRAEQASQ---EVKNWMTETLLVQNANPDC 329 RSV:5a9e 96 KGLADGMVGNPQGQAAL---LRPGEL-VAITASALQAFREVARLAEPA------GPWADI----TQGP--SESFVDFANRLIKAVEGSDLPP---TARAPVIIDCFRQKSQPDI 189 BLV:4ph0 88 NPQN---GTLTQQSAQP----NAGDLRSQYQNLWLQAWKNLPTRPS------VQPWSTI----VQGP--AESYVEFVNRLQISLADNLPDG---VPKEPIIDSLSYANANKEC 177 http://jvi.asm.org/ JSRV 82 EMLIGEGPYQATDTQLN---FLPGAY-AQISNAARQAWKKLPSSSTKT------EDLSKV----RQGP--DEPYQDFVARLLDTIGKIMSDE---KAGMVLAKQLAFENANSAC 175 LPDV 88 VLKGSDPAMATPQLQAA--RMRGREIQASCQASVSICGGRTVGKRT------DPWTKV----TQGL--GEPFLSFAERLLNAYEKSQLPE---AAKNAVFRDCVKQQGNMLT 181 MMTV 83 DMLLGTGQFLSPSSQIK----LSKDVLKDVTTNAVLAWRAIPPPGVKK------TVLAGL----KQGN--EESYETFISRLEEAVYRMMPRG---EGSDILIKQLAWENANSLC 176

Retroviridae MPMV 83 DMLTGSGNYSSTDAQMQ---YDPGLF-AQIQAAATKAWRKLPVKGDPG------ASLTGV----KQGP--DEPFADFVHRLITTAGRIFGSA---EAGVDYVKQLAYENANPAC 176 PyERV 81 DDVLGTGTISTIAQQQN----SDRAAFPIIKNCALAALRKVDDNQGKP------LQTFSKI---I-QSP--TEDYSSFISRLQVALERQIDNV---DARGELCMKLAYENANSDC 175 EIAV:2eia 88 ARFIRGLGVPRERQMEP----AFDQFRQTYRQWIIEAMSEGIKVMIGK------PKAQNI----RQGA--KEPYPEFVDRLLSQIKSEGHPQ---EISKFLTDTLTIQNANEEC 181 Amn-ni 68 ------SYMAFEQEFKRVFDHPLSD------RQASKKLLTL----RQGT---GSVAEYAIQFRTVAAGSGWN------DEAFMVCFQNGLSEII 135 Beetle1 71 ------SWKKLKKKMEAKFLPSTYT------LDLYNQLSDL----FQGT---KNVETYIHEYEKLMMKLDVQE-----REEQTMARFVKGLDRDI 140 Blastopia 76 ------GYTELKELLIEEFSGSYNS------AVIHKKLQDR---K-KKR--EETLHDYLLQMKKIAALGEV------ETVALITHIVNGLDIKK 144 Cer4 66 ------PFVTTVEALEKALGSHRSL------MIRRQTCLHL-S-RTNCT--SLDPLKWTNQISEAVLDAELAKMS---TSDWGIFLFLKGLDAPG 140 DRM 65 ------LYQEIVDTLKSHFEPKPLL------IAERFRFNHC-NQRA-----DETVTEYAAELKQCAVSCEFGA----TLDEALRDRFVSGIRNEA 136 Hydra2-1 65 ------SYTELCRLMSTHKSPTPNP------IAERFKFNSR-N-R--DT--SESVATFIADLRALTTHCAYEN----TLDEMMRDRIVCGINDSR 136

Metaviridae Micropia 69 ------TWQEFQELFLQRFETEE------TPAATFLNLLNSR--PTA-AECYAVYASRLVTQLTTKWRNM---EIEEIAVTTVLAHMANIDS 141

Osvaldo 75 ------TWGTFVRSFQEFFFAEDYL------EDLKDEVKRR---KQMV---DEPFKIYMVEMQTLMRPLRYGP------DHE-MKLIYNNSIPDL 143 on January 30, 2019 by guest Ty3-1 67 ------TFDTFIQGLYQHFYKPPD------INKIFNAITQL-----SEA--KLGIERLNQRFRKIWDRMPPD----FMTEKAAIMTYTRLLTKET 137 Bel 63 ------NYREAWERLEQRY-NKQSLI------IRSFLNSFMSL--PSAINS-NIGTVRKIADGADEVIRGLRALNC--EERDPWLIFILLSKLDSDT 140 Pao 58 ------DPSDVIRSLEARFGRPETI------AITELDTLRAL--PRLTET--PRDICIFSSKVTNAVATLRALNCTHYLYNPETTKTMLEKLTPTL 136 Copia 69 ------TARQILENLDAVYERKSLA------SQLALRKRLLSL---KLSS---EMSLLSHFHIFDELISELLAAGA--KIEEMDKISHLLITLPSCY 144 Fourf 57 ------TGKELWDALVGKFGVTDAGSE------LYLMEQLYDY---KMV-E--NRSVVEQAHEFQALAKELELFPC--PLPDKFVAGGIIAKLPPSW 132 Oryco1-2 59 ------LATLAVKETVQEAWEAIKTRRIGVQHV-REANAQQLRREFGDI----IFKD--GETVDDFSMRIGVLANNLRTLGDN-ITDAEVVQKLL-QVVPEHL 145 BSGFV 146 GNN------GTQNILNQIRMIFFLENPKVGTTDE------QDAAY-KTIKS---LVCNEMTDKAVYRYMNDYFHLASKSGRMW-----ANEELSTEFFTKLPRHL 228

Pseudoviridae BSOLV 148 GDQ------GTQNIINQIRLIFFLENPQVGTTTS------QDAAY-KTLKS---LVCTEMTDTAIYRYMNDYFHLSAKTGRAW-----ASEELSKEFFTKLPRGL 230 CaMV 66 ------IIEQVIDAMYTMFLGLNYSDNKVAE--KIDEQEKAKIRMTKL---QLCD---ICYLEEFTCDYEKNMYKTELA------DFPGYINQYLSKIPII- 146 CERV 73 ------ILLNVVSGLYTMFLGEDYTGNQEKT--LEQERAKASLRLINL---QLCD---ICSLQSFFCDYESNLYKLPQN------EYPSLVKQYLAKIPIV- 153 CSSV 153 GRQ------GTQNILSQIKRIFSLEDPASGSTRI------QDAAY-RDLER---LTCHN--IKDIVQFLNDYGRLAAKSGRLF-----LGTELSEKLWMKMPPEL 233 DBV 148 GRE------GTQNIISQIRTIFSLEDPFRGSTKI------QEDAY-RDLER---ISCKD--VQDIIPFMNEYMRIAAKTGRLF-----ISSELSEKFWMKLPGDL 228 DrMV 157 ------DSQAIISQVRRIITLEDPSQGSTEE------QDRAY-MDLGR---LSCTN--MKDLLDYMNDYKTLAAKSGRMY-----VNHELSDKFFDKMPQII 234 Caulimoviridae MiMV 71 ------TPQDVAAGLYTMFVGVDYATDQANQ--IRLEKEKAKQTLTNA---QLCD---ICLLDDFTCLFEKNLVHFEMS------EMPAWVETYLRKIPIV- 151 TaBV 146 ------ETQNLLSQVRRIFLLQDPYQGSTAE------QDQAYNDLERI----SCDN--IKDLIPYLIQFRNLAAKSGRLF-----LGPELSEKLFRKMPPLI 223

α10 α11 NC **** **** HIV-1:4d1k 330 CK----TILKALGP------AATLEEMMTAC--QGVG--GPGHKARV--(25)--KIVKCFNCGKE------GHT----ARNC---(4)--KKGCWKCGKEGHQMKDCTER 430 RSV:5a9e 190 IQ----QLIRAAPST------LTTPGEIIKYVLDRQKT--APLTDQGI--(24)------(2)--RGLCYTCGSPGHYQAQCPKK 276 BLV:4ph0 178 CQ----QILQGRGLV------AAPVGQKLQAC--AHWA--PKVKQPAI--(23)------(7)--PGPCYRCLKEGHWARDCPTK 253 JSRV 176 CQ----AALRPYRK------KGDLSDFIRIC--ADIG--PSYMQGIA--(14)--GNSGCFVCGQP------GHR----AAVC---(7)--PNLCPRCKKGKHWARDC--- 281 LPDV 182 TQ----QYMLGAPST------ENTAELVKYLLKRE--NEGAAQGN--(28)------(10)--GANCFKCGAVGHMRRDCPSL 248 MMTV 177 CQ----DLIRPIRK------TGTIQDYIRAC--LDAS--PAVVQGMA---(9)--EGPVCFSCGKT------GHI----RKDC---(4)--PGLCPRCKKGYHWKSEC--- 281

Retroviridae MPMV 177 CQ----AAIRPYRK------KTDLTGYIRLC--SDIG--PSYQQGLA--(27)----GCCFKCGKK------GHF----AKNC--(10)--PGLCPRCKRGKHWANEC--- 276 PyERV 176 CQ----KVLQPIANKP-----GITLADFLQAC--RIVG--TTSHKMAA--(22)------(12)--AGNCFNCGKPGHFKSQCRAP 259 EIAV:2eia 182 CR----NAMRHLRP------EDTLEEKMYAC--RDIG--TTKQKMML--(21)--AAQTCYNCGKP------GHL----SSQC---(7)--PKVCFKCKQPGHFSKQC--- 275 Amn-ni 136 IQ----DDLATREP------ALDLESLIDQA--IKLD--NRLRERHL--(24)--PEPMQLGRTRL------SPT------(7)--ERCCLYCGLSDHFRSTC--- 230 Beetle1 141 IQ----KKLELQS------YSTLDELFRLA--LKVE--KHQKDKKK--(28)--KSEAGSKFLDK------GKK----VAES---(5)--DIKCFKCHGYGHYQAQC--- 240 Blastopia 145 KEYKG-AMLRCK------TLKELKQEF--EIYE--SLNIVDKP--(13)--KADHCFNCGSR------EHK----RKDC---(2)--PTKCFSCNQEGHISSKC--- 226 Cer4 141 GDAQAKAYLMQFYETSDRKGEKLTLSNMHDEW--VRFL--QTKSQTKI--(20)----PKKPAYIAA------DAK----SDPP---(5)--VITCYRCGAAGHMQYDC--- 242 DRM 137 ACQ---RRLLSES------NLTFARAFEIA--LSME--TAEKDTQQ--(21)--REKKCYRCHGK------NHS----AQVC---(3)--DARCHNCGKIGHIKRAC--- 228 Hydra2-1 137 RIQ---RRLLSEGS------NLSLQKTLDIV--LTME--AAANQAAI--(23)--IERECFRCGG------KHN----PETC---(3)--DQECFFCHNKGHTTKKC--- 230

Metaviridae Micropia 142 SRLQ--RVLFTSN------VRTRSKLQAEL--KAFTFDKKRHARDD--(11)--SPVVCHFCSKP------GRR----IAEC--(17)--NVTCYRCGQPGHFSNQC--- 240 Osvaldo 144 LR----AYARPYQ------FQSLMELMKLA--DEFE--ELERDRER--(33)--SPRPAPRTGAT------GQR------(6)--SRACRVCGQEGHRAVRCRNR 249 Ty3-1 138 TY----NIVRMHK------PETLKDAMEEA--YQTT--ALTERFFP--(41)--RTRRSYNKPMS------NHR----NRRN--(10)--NRLCFYCKKEGHRLNEC--- 255 Bel 141 TR----QAWAQCAES-EEK--GVTINRFLKFL--TSRC--DTLEAFEL--(21)--EEPKCTSCQQ------NHQ----LFKC--(17)--RKLCFNCLSPAHMVGNCTSR 253 Pao 137 LR----YRYYDFTAVQPKE--DPDLIKFEKFM--KREA--ELCSPYAQ---(6)--RAKCPVCSNT------EHT----TTDC--(17)--KHLCFRCLQYKNKTHNCKPK 257 Copia 145 YD----GIITAIETL-SEE--NLTLAFVKNRL--LDQE--IKIKNDHN--(33)------(7)--KVKCHHCGREGHIKKDC--- 238 Fourf 133 WKDFA-TSLKHKRQ------EFNVEELIGTL--DVEE--RARTKDSG--(23)--NQNKPENANKP------VHT------(12)--KGGCFVCGSDQHWAREC--- 234 Oryco1-2 146 LQQIA-ISIETLLDVN-----ELSLEEVTGSL--RSVE--QRKQRKAV--(32)--AHSSSGGNSDR------QGQG----RGNK--(19)--PGNCKNCGKRGHWAKDC--- 270 229 LGDKVEKAFKERHPTN-----SIGVTARIAFT--RNYL--KDMCQEAL---(6)--KMNFCGNTPVH------GIYG----KNKE--(36)--DCKCFACGETGHYASECTNP 349

Pseudoviridae BSGFV BSOLV 231 LGDEVEKAFMEKHPSN-----TVGITARITFT--KRYL--KELCEKVA--(17)--KMDFCRSTPVH------GLY----RDKS--(34)--NCRCYACGEEGHFASECKNP 348 CaMV 147 -GEKALTRFRHEAN--GTS--IYSLGFAAKIV--KEEL--SKICDLSK--(17)---ASTEYGCKKTSTKKYHKKRYKKK-YKAYKP--(31)--DCRCWICNIEGHYANECPNR 283 CERV 154 -GEKASKRFEEEAS--AAT--SYSLGFAHKLV--NEEL--AKICELSK---(6)---KPYEYGCKPSYSKKKKYSKKYKPKYTKYKV--(31)--TCRCWVCNIEGHYANECPNR 291 CSSV 234 LGHRMKEAFQKEYSGN-----EVGVFPRILFA--YRYL--EQECKDAA---(6)--SLSFCKDMPLT------GYY----DK-T--(32)--KCKCYLCGDEGHFARECPNQ 348 DBV 229 LGKTIKDSFDKTYVGN-----TVGVHPRILFT--YKYL--QEECKKAA---(6)--NLQFCSKIPIP------GYY----KGRE--(32)--KCKCFLCGAEGHFARECPND 344 DrMV 235 IGPDMKKAFSEKYPGA-----QMGVLPRITFA--YKYL--SDICKQAA---(6)--DLAFCRRIPLP------GYY----KDGP--(33)--KCRCYICGQEGHFARECRNG 351 Caulimoviridae MiMV 152 -GEISRMIYNETKS--PAT--TYSLAFATRIV--KTEI--AKICEARS--(19)--SENNQFGCNKPSYSSKRKKYEKS---RRKVW--(34)--KCRCWICSEEGHYANECPNR 292 TaBV 224 IGKEIETAFIAKHGNA-----NITVMPRIHFA--YHYL--AELCKKAA---(6)--DLSFCNQIPLP------GIY----TKGN--(32)--KCKCFICGEPGHFARECTKQ 339 Downloaded from http://jvi.asm.org/ on January 30, 2019 by guest