Volume 12, Number 9—September 2006
Research
Genomic Signatures of Human versus Avian Influenza A Viruses
Table 1
Validated amino acid signatures separating avian influenza viruses from human influenza viruses*
Gene | Position | Avian residues | Human residues | Associated functional domains |
---|---|---|---|---|
PB2 | 44 | A(208),S(7) | S(831),A(10),L(2) | PB1–1, NP-1 (9), MLS (10) |
199 | A(210),S(5) | S(842),A(3) | NP-1 (9) | |
271 | T(210),A(3),I(1),M(1) | A(836),T(6),S(1) | Cap-N (11) | |
475 | L(214),M(1) | M(839),L(3) | NLS (12) | |
588 | A(203),T(6),V(6) | I(835),V(3),A(2) | PB1–2, NP-2 (9) | |
613 | V(212),A(3) | T(816),I(16),A(8),V(1) | PB1–2, NP-2 (9) | |
627 | E(196),K(19) | K(838),R(2),E(1) | PB1–2, NP-2 (9) | |
674 | A(204),S(6),T(2),G(2),E(1) | T(836),A(2),I(2),P(1) | PB1–2, NP-2 (9) | |
PB1 | 327 | R(147),K(3) | K(766),R(66) | cRNA (13) |
336 | V(142),I(8) | I(773),V(59) | cRNA (13) | |
PB1-F2 | 73 | K(397),R(6),I(1) | R(594),K(87),S(1) | ANT3, VDAC1 (14), mitochondrial localization (15), predicted amphipathic helix (16) |
76 | V(401),A(3) | A(625),V(57) | ANT3, VADC1 (14), predicted amphipathic helix (16) | |
79 | R(369),Q(34),L(1) | Q(607),R(75) | ANT3, VADC1 (14), predicted amphipathic helix (16) | |
82 | L(382),S(22) | S(596),L(86) | ANT3, VADC1 (14), predicted amphipathic helix (16) | |
87 | E(389),G(14),K(1) | G(637),E(45) | ANT3, VADC1 (14) | |
PA | 28 | P(213),S(1) | L(831),P(9),R(2) | Proteolysis (17) |
55 | D(214) | N(836),D(5) | Proteolysis (17) | |
57 | R(210),Q(4) | Q(829),R(6),L(4),K(2) | Proteolysis (17) | |
225 | S(213),C(1) | C(829),S(10) | Proteolysis (17), NLSII (18) | |
268 | L(214) | I(827),L(11), P(1) | ||
356 | K(212),X(1),R(1) | R(827),K(11) | ||
382 | E(208),D(5),V(1) | D(824),E(11),V(2),N(1) | ||
404 | A(214) | S(828),A(9),P(1) | ||
409 | S(189),N(24),I(1) | N(830),S(7),I(1) | ||
552 | T(213),N(1) | S(835),T(1),I(1) | ||
HA | 237 | N(582),R(49),D(2),H(1),S(1) | R(1209),N(12),S(2),D(1),K(1) | |
389 | D(659),N(20),G(1),Y(1) | N(819),D(121) | ||
NP | 16 | G(356),S(9),D(6),T(2) | D(646),G(7) | RNA binding (19), BAT1/UAP56 (20), MxA (21), PB2–1 (22) |
33 | V(355),I(18) | I(638),V(15) | RNA binding (19), MxA (21), PB2–1 (22) | |
61 | I(366),M(6),V(1) | L(642),I(8) | RNA binding (19), MxA (21), PB2–1 (22) | |
100 | R(360),K(11),V(2) | V(619),I(32),A(1),M(1) | RNA binding (19), MxA (21), PB2–1 (22) | |
109 | I(359),V(10),M(2),T(2) | V(614),I(34),T(3),A(2) | RNA binding (19), MxA (21), PB2–1 (22) | |
214 | R(352),K(20),L(1) | K(640),R(10) | NLS (23), CRM1 (24), NP-1 (25) | |
283 | L(372),P(1) | P(643),L(7) | NP-1 (25), PB2–2 (22) | |
293 | R(371),K(2) | K(622),R(28) | NP-1 (25), PB2–2 (22) | |
305 | R(369),K(4) | K(636),R(14) | NP-1 (25), PB2–2 (22) | |
313 | F(371),I(1),L(1) | Y(642),F(8) | NP-1 (25), PB2–2 (22) | |
357 | Q(368),K(4),T(1) | K(644),R(8),Q(1) | NAS (26), NP-1 (25), PB2–3 (22) | |
372 | E(357),D(15),K(1) | D(630),E(23) | NAS (26), NP-2 (25), PB2–3 (22) | |
422 | R(373) | K(630),R(23) | CTL epitope (27), NP-2 (25), PB2–3 (22) | |
442 | T(372),A(1) | A(629),T(23),R(1) | NP-2 (25), PB2–3 (22) | |
455 | D(373) | E(630),D(22),T(1) | NP-2 (25), PB2–3 (22) | |
M1 | 115 | V(856),I(2),L(1),G(1) | I(981),V(9) | |
121 | T(840),A(19),P(1) | A(988),T(2) | ||
137 | T(859),A(1),P(1) | A(974),T(12) | ||
M2 | 11 | T(434),I(11),S(2) | I(911),T(44) | Host restriction specificities (28), ectodomain (29) |
20 | S(471),N(13) | N(926),S(29) | Host restriction specificities (28). ectodomain (29) | |
57 | Y(481),C(1),H(1) | H(913),Y(33),R(2),Q(1) | CRAC (30), endodomain (29) | |
86 | V(378) | A(924),V(10),T(4),D(1) | Endodomain (29) | |
NS1 | 227 | E(692),G(9),K(1),S(1) | R(897),G(5),K(1),E(1) | |
NS2 | 70 | S(453),G(21),D(1) | G(903),S(2) | M1, NEP dimerization domain (31) |
107 | L(468),S(2),F(1) | F(777),L(16),S(1) | M1, NEP dimerization domain (31) |
*Numbers in parentheses in residue columns are the number of sequences yielding the specific amino acid residue; bold indicates dominant amino acid residue type.
References
- Scholtissek C, Rohde W, von Hoyningen V, Rott R. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology. 1978;87:13–20. DOIPubMedGoogle Scholar
- Reid AH, Taubenberger JK, Fanning TG. Evidence of an absence: the genetic origins of the 1918 pandemic influenza virus. Nat Rev Microbiol. 2004;2:909–14. DOIPubMedGoogle Scholar
- Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature. 2005;437:889–93. DOIPubMedGoogle Scholar
- Chang SC, Cheng YY, Shih SR. Avian influenza virus: the threat of a pandemic. Chang Gung Med J. 2006;29:130–4.PubMedGoogle Scholar
- Rice P, Longden I, Bleasby A. EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet. 2000;16:276–7. DOIPubMedGoogle Scholar
- Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symposium Series. Oxford: Oxford University Press; 1999. p. 95–8.
- Chen GW, Hsiung CA, Chyn JL, Shih SR, Wen CC, Chang IS. Revealing molecular targets for enterovirus type 71 detection by profile hidden Markov models. Virus Genes. 2005;31:337–47. DOIPubMedGoogle Scholar
- Macken C, Lu H, Goodman J, Boykin L, Boykin L. The value of a database in surveillance and vaccine selection. In: Osterhaus A, Cox N, Hampson AW, editors.Options for the control of influenza IV. Amsterdam: Elsevier Science; 2001. p. 103–6.
- Poole E, Elton D, Medcalf L, Digard P. Functional domains of the influenza A virus PB2 protein: identification of NP- and PB1-binding sites. Virology. 2004;321:120–33. DOIPubMedGoogle Scholar
- Carr SM, Carnero E, Garcia-Sastre A, Brownlee GG, Fodor E. Characterization of a mitochondrial-targeting signal in the PB2 protein of influenza viruses. Virology. 2006;344:492–508. DOIPubMedGoogle Scholar
- Honda A, Mizumoto K, Ishihama A. Two separate sequences of PB2 subunit constitute the RNA cap-binding site of influenza virus RNA polymerase. Genes Cells. 1999;4:475–85. DOIPubMedGoogle Scholar
- Mukaigawa J, Nayak DP. Two signals mediate nuclear localization of influenza virus (A/WSN/33) polymerase basic protein 2. J Virol. 1991;65:245–53.PubMedGoogle Scholar
- Gonzalez S, Ortin J. Distinct regions of influenza virus PB1 polymerase subunit recognize vRNA and cRNA templates. EMBO J. 1999;18:3767–75. DOIPubMedGoogle Scholar
- Zamarin D, Garcia-Sastre A, Xiao X, Wang R, Palese P. Influenza virus PB1–F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLoS Pathog. 2005;1:e4. DOIPubMedGoogle Scholar
- Yamada H, Chounan R, Higashi Y, Kurihara N, Kido H. Mitochondrial targeting sequence of the influenza A virus PB1–F2 protein and its function in mitochondria. FEBS Lett. 2004;578:331–6. DOIPubMedGoogle Scholar
- Gibbs JS, Malide D, Hornung F, Bennink JR, Yewdell JW. The influenza A virus PB1–F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function. J Virol. 2003;77:7214–24. DOIPubMedGoogle Scholar
- Sanz-Ezquerro JJ, Zurcher T, de la Luna S, Ortin J, Nieto A. The amino-terminal one-third of the influenza virus PA protein is responsible for the induction of proteolysis. J Virol. 1996;70:1905–11.PubMedGoogle Scholar
- Nieto A, de la Luna S, Barcena J, Portela A, Ortin J. Complex structure of the nuclear translocation signal of influenza virus polymerase PA subunit. J Gen Virol. 1994;75:29–36. DOIPubMedGoogle Scholar
- Albo C, Valencia A, Portela A. Identification of an RNA binding region within the N-terminal third of the influenza A virus nucleoprotein. J Virol. 1995;69:3799–806.PubMedGoogle Scholar
- Momose F, Basler CF, O'Neill RE, Iwamatsu A, Palese P, Nagata K. Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis. J Virol. 2001;75:1899–908. DOIPubMedGoogle Scholar
- Turan K, Mibayashi M, Sugiyama K, Saito S, Numajiri A, Nagata K. Nuclear MxA proteins form a complex with influenza virus NP and inhibit the transcription of the engineered influenza virus genome. Nucleic Acids Res. 2004;32:643–52. DOIPubMedGoogle Scholar
- Biswas SK, Boutz PL, Nayak DP. Influenza virus nucleoprotein interacts with influenza virus polymerase proteins. J Virol. 1998;72:5493–501.PubMedGoogle Scholar
- Weber F, Kochs G, Gruber S, Haller O. A classical bipartite nuclear localization signal on Thogoto and influenza A virus nucleoproteins. Virology. 1998;250:9–18. DOIPubMedGoogle Scholar
- Elton D, Simpson-Holley M, Archer K, Medcalf L, Hallam R, McCauley J, Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway. J Virol. 2001;75:408–19. DOIPubMedGoogle Scholar
- Elton D, Medcalf E, Bishop K, Digard P. Oligomerization of the influenza virus nucleoprotein: identification of positive and negative sequence elements. Virology. 1999;260:190–200. DOIPubMedGoogle Scholar
- Bullido R, Gomez-Puertas P, Albo C, Portela A. Several protein regions contribute to determine the nuclear and cytoplasmic localization of the influenza A virus nucleoprotein. J Gen Virol. 2000;81:135–42.PubMedGoogle Scholar
- Berkhoff EG, de Wit E, Geelhoed-Mieras MM, Boon AC, Symons J, Fouchier RA, Functional constraints of influenza A virus epitopes limit escape from cytotoxic T lymphocytes. J Virol. 2005;79:11239–46. DOIPubMedGoogle Scholar
- Liu W, Zou P, Ding J, Lu Y, Chen YH. Sequence comparison between the extracellular domain of M2 protein human and avian influenza A virus provides new information for bivalent influenza vaccine design. Microbes Infect. 2005;7:171–7. DOIPubMedGoogle Scholar
- Lamb RA, Zebedee SL, Richardson CD. Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface. Cell. 1985;40:627–33. DOIPubMedGoogle Scholar
- Schroeder C, Heider H, Moncke-Buchner E, Lin TI. The influenza virus ion channel and maturation cofactor M2 is a cholesterol-binding protein. Eur Biophys J. 2005;34:52–66. DOIPubMedGoogle Scholar
- Akarsu H, Burmeister WP, Petosa C, Petit I, Muller CW, Ruigrok RW, Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2). EMBO J. 2003;22:4646–55. DOIPubMedGoogle Scholar
- Fouchier RA, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster V, Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci U S A. 2004;101:1356–61. DOIPubMedGoogle Scholar
- Subbarao EK, London W, Murphy BR. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol. 1993;67:1761–4.PubMedGoogle Scholar
- Obenauer JC, Denson J, Mehta PK, Su X, Mukatira S, Finkelstein DB, Large-scale sequence analysis of avian influenza isolates. Science. 2006;311:1576–80. DOIPubMedGoogle Scholar
- Chen Z, Krug RM. Selective nuclear export of viral mRNAs in influenza-virus-infected cells. Trends Microbiol. 2000;8:376–83. DOIPubMedGoogle Scholar
- Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, A novel influenza A virus mitochondrial protein that induces cell death. Nat Med. 2001;7:1306–12. DOIPubMedGoogle Scholar
- Chen GW, Yang CC, Tsao KC, Huang CG, Lee LA, Yang WZ, Influenza A virus PB1–F2 gene in recent Taiwanese isolates. Emerg Infect Dis. 2004;10:630–6.PubMedGoogle Scholar
1These authors contributed equally to this article.