Conserved GXXXG-and S/T-like motifs in the transmembrane domains of NS4B protein are required for hepatitis C virus replication

Journal of Virology

Volumn 85, Issue 13, 2011, Pages 6464-6479

  Han, Qingxia ^a   Aligo, Jason ^a   Manna, David ^a   Belton, Kerry ^a   Chintapalli, Sree V ^a,b   Hong, Yoojin ^b,c   Patterson, Randen L ^a,b   van Rossum, Damian B ^a,b   Konan, Kouacou V ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

^b PENNSYLVANIA STATE UNIVERSITY   (United States)

^c The Pennsylvania State University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MEMBRANE PROTEIN; MUTANT PROTEIN; NONSTRUCTURAL PROTEIN 4B; NS4B PROTEIN, FLAVIVIRUS; VIRUS PROTEIN; VIRUS RNA;

ADAPTATION; AMINO ACID SEQUENCE; ARTICLE; CELL MEMBRANE; CHIMERA; CONTROLLED STUDY; CORRELATION ANALYSIS; DIMERIZATION; GENE MAPPING; GENE REPLICATION; GENOME; HEPATITIS C VIRUS; HOST; HUMAN; HUMAN CELL; MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN MOTIF; PROTEIN STABILITY; PROTEIN STRUCTURE; VIRUS LOAD; VIRUS REPLICATION; CHEMISTRY; CLASSIFICATION; CONSENSUS SEQUENCE; GENETICS; METABOLISM; MOLECULAR GENETICS; PHYSIOLOGY; PROTEIN MULTIMERIZATION; SEQUENCE ALIGNMENT; STRUCTURE ACTIVITY RELATION; TUMOR CELL LINE;

HEPATITIS C VIRUS;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; CELL LINE, TUMOR; CELL MEMBRANE; CONSENSUS SEQUENCE; HEPACIVIRUS; HUMANS; MOLECULAR SEQUENCE DATA; MUTATION; PROTEIN MULTIMERIZATION; RNA, VIRAL; SEQUENCE ALIGNMENT; STRUCTURE-ACTIVITY RELATIONSHIP; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 80052056964     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.02298-10     Document Type: Article

References (77)

1. Adamian, L., and J. Liang. 2001. Helix-helix packing and interfacial pairwise interactions of residues in membrane proteins. J. Mol. Biol. 311:891-907.
2. Ali, N., K. D. Tardif, and A. Siddiqui. 2002. Cell-free replication of the hepatitis C virus subgenomic replicon. J. Virol. 76:12001-12007.
3. Aligo, J., S. Jia, D. Manna, and K. V. Konan. 2009. Formation and function of hepatitis C virus replication complexes require residues in the carboxyterminal domain of NS4B protein. Virology 393:68-83.
4. Alter, M. J. 1997. Epidemiology of hepatitis C. Hepatology 26:62S-65S.
5. Appel, N., et al. 2008. Essential role of domain III of nonstructural protein 5A for hepatitis C virus infectious particle assembly. PLoS Pathog. 4:e1000035.
6. Asundi, V. K., and D. J. Carey. 1995. Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region. J. Biol. Chem. 270: 26404-26410.
7. Bartenschlager, R., and S. Sparacio. 2007. Hepatitis C virus molecular clones and their replication capacity in vivo and in cell culture. Virus Res. 127:195-207.
8. Berger, B. W., et al. 2010. Consensus motif for integrin transmembrane helix association. Proc. Natl. Acad. Sci. U. S. A. 107:703-708.
9. Blight, K. J. 2007. Allelic variation in the hepatitis C virus NS4B protein dramatically influences RNA replication. J. Virol. 81:5724-5736.
10. Blight, K. J., A. A. Kolykhalov, and C. M. Rice. 2000. Efficient initiation of HCV RNA replication in cell culture. Science 290:1972-1974.
11. Blight, K. J., J. A. McKeating, and C. M. Rice. 2002. Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. J. Virol. 76:13001-13014.
12. Carrillo, J. J., J. F. Lopez-Gimenez, and G. Milligan. 2004. Multiple interactions between transmembrane helices generate the oligomeric 1b-adrenoceptor. Mol. Pharmacol. 66:1123-1137.
13. Ciczora, Y., N. Callens, F. Penin, E. I. Pecheur, and J. Dubuisson. 2007. Transmembrane domains of hepatitis C virus envelope glycoproteins: residues involved in E1E2 heterodimerization and involvement of these domains in virus entry. J. Virol. 81:2372-2381.
14. Cleverley, D. Z., and J. Lenard. 1998. The transmembrane domain in viral fusion: essential role for a conserved glycine residue in vesicular stomatitis virus G protein. Proc. Natl. Acad. Sci. U. S. A. 95:3425-3430.
15. Dawson, J. P., J. S. Weinger, and D. M. Engelman. 2002. Motifs of serine and threonine can drive association of transmembrane helices. J. Mol. Biol. 316:799-805.
16. Egger, D., et al. 2002. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J. Virol. 76:5974-5984.
17. Einav, S., M. Elazar, T. Danieli, and J. S. Glenn. 2004. A nucleotide binding motif in hepatitis C virus (HCV) NS4B mediates HCV RNA replication. J. Virol. 78:11288-11295.
18. Einav, S., et al. 2008. Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis. Nat. Biotechnol. 26:1019-1027.
19. Einav, S., et al. 2008. The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection. Hepatology 47:827-835.
20. Elazar, M., P. Liu, C. M. Rice, and J. S. Glenn. 2004. An N-terminal amphipathic helix in hepatitis C virus (HCV) NS4B mediates membrane association, correct localization of replication complex proteins, and HCV RNA replication. J. Virol. 78:11393-11400.
21. El-Hage, N., and G. Luo. 2003. Replication of hepatitis C virus RNA occurs in a membrane-bound replication complex containing nonstructural viral proteins and RNA. J. Gen. Virol. 84:2761-2769.
22. Eswar, N., et al. 2007. Comparative protein structure modeling using MODELLER. Curr. Protoc. Protein Sci. Chapter 2: Unit 2.9.
23. Eswar, N., et al. 2006. Comparative protein structure modeling using Modeller. Curr. Protoc. Bioinformatics Chapter 5: Unit 5.6.
24. Gosert, R., et al. 2003. Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J. Virol. 77:5487-5492.
25. Gouttenoire, J., et al. 2009. Identification of a novel determinant for membrane association in hepatitis C virus nonstructural protein 4B. J. Virol. 83:6257-6268.
26. Gouttenoire, J., R. Montserret, A. Kennel, F. Penin, and D. Moradpour. 2009. An amphipathic-helix at the C terminus of hepatitis C virus nonstructural protein 4B mediates membrane association. J. Virol. 83:11378-11384.
27. Guo, J. T., V. V. Bichko, and C. Seeger. 2001. Effect of alpha interferon on the hepatitis C virus replicon. J. Virol. 75:8516-8523.
28. Han, Q., et al. 2009. Compensatory mutations in NS3 and NS5A proteins enhance the virus production capability of hepatitis C reporter virus. Virus Res. 145:63-73.
29. Huang, L., et al. 2005. Hepatitis C virus nonstructural protein 5A (NS5A) is an RNA-binding protein. J. Biol. Chem. 280:36417-36428.
30. Hügle, T., et al. 2001. The hepatitis C virus nonstructural protein 4B is an integral endoplasmic reticulum membrane protein. Virology 284:70-81.
31. Ishido, S., T. Fujita, and H. Hotta. 1998. Complex formation of NS5B with NS3 and NS4A proteins of hepatitis C virus. Biochem. Biophys. Res. Commun. 244:35-40.
32. Itoh, R., and Y. Fujiki. 2006. Functional domains and dynamic assembly of the peroxin Pex14p, the entry site of matrix proteins. J. Biol. Chem. 281: 10196-10205.
33. Jones, D. M., A. H. Patel, P. Targett-Adams, and J. McLauchlan. 2009. The hepatitis C virus NS4B protein can trans-complement viral RNA replication and modulates production of infectious virus. J. Virol. 83:2163-2177.
34. Kato, T., et al. 2003. Efficient replication of the genotype 2a hepatitis C virus subgenomic replicon. Gastroenterology 125:1808-1817.
35. Kim, D. W., Y. Gwack, J. H. Han, and J. Choe. 1995. C-terminal domain of the hepatitis C virus NS3 protein contains an RNA helicase activity. Biochem. Biophys. Res. Commun. 215:160-166.
36. Kleiger, G., R. Grothe, P. Mallick, and D. Eisenberg. 2002. GXXXG and AXXXA: common alpha-helical interaction motifs in proteins, particularly in extremophiles. Biochemistry 41:5990-5997.
37. Konan, K. V., et al. 2003. Nonstructural protein precursor NS4A/B from hepatitis C virus alters function and ultrastructure of host secretory apparatus. J. Virol. 77:7843-7855.
38. Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-685.
39. Langosch, D., and I. T. Arkin. 2009. Interaction and conformational dynamics of membrane-spanning protein helices. Protein Sci. 18:1343-1358.
40. Liefhebber, J. M., B. W. Brandt, R. Broer, W. J. Spaan, and H. C. van Leeuwen. 2009. Hepatitis C virus NS4B carboxy terminal domain is a membrane binding domain. Virol. J. 6:62.
41. Lindenbach, B. D., et al. 2005. Complete replication of hepatitis C virus in cell culture. Science 309:623-626.
42. Lindström, H., M. Lundin, S. Haggstrom, and M. A. Persson. 2006. Mutations of the hepatitis C virus protein NS4B on either side of the ER membrane affect the efficiency of subgenomic replicons. Virus Res. 121:169-178.
43. Lohmann, V., et al. 1999. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285:110-113.
44. Lundin, M., M. Monne, A. Widell, G. Von Heijne, and M. A. Persson. 2003. Topology of the membrane-associated hepatitis C virus protein NS4B. J. Virol. 77:5428-5438.
45. Luo, B. H., T. A. Springer, and J. Takagi. 2004. A specific interface between integrin transmembrane helices and affinity for ligand. PLoS Biol. 2:e153.
46. Ma, Y., J. Yates, Y. Liang, S. M. Lemon, and M. Yi. 2008. NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly. J. Virol. 82:7624-7639.
47. MacKenzie, K. R., J. H. Prestegard, and D. M. Engelman. 1997. A transmembrane helix dimer: structure and implications. Science 276:131-133.
48. Manna, D., et al. 2010. Endocytic Rab proteins are required for hepatitis C virus replication complex formation. Virology 398:21-37.
49. Martí-Renom, M. A., et al. 2000. Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct. 29:291-325.
50. Masaki, T., et al. 2008. Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles. J. Virol. 82:7964-7976.
51. Miller, R. H., and R. H. Purcell. 1990. Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proc. Natl. Acad. Sci. U. S. A. 87:2057-2061.
52. Miyauchi, K., et al. 2006. Mutations of conserved glycine residues within the membrane-spanning domain of human immunodeficiency virus type 1 gp41 can inhibit membrane fusion and incorporation of Env onto virions. Jpn. J. Infect. Dis. 59:77-84.
53. Moradpour, D., F. Penin, and C. M. Rice. 2007. Replication of hepatitis C virus. Nat. Rev. Microbiol. 5:453-463.
54. Munter, L. M., et al. 2007. GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of A 42. EMBO J. 26:1702-1712.
55. Op De Beeck, A., et al. 2000. The transmembrane domains of hepatitis C virus envelope glycoproteins E1 and E2 play a major role in heterodimerization. J. Biol. Chem. 275:31428-31437.
56. Paredes, A. M., and K. J. Blight. 2008. A genetic interaction between hepatitis C virus NS4B and NS3 is important for RNA replication. J. Virol. 82:10671-10683.
57. Pietschmann, T., et al. 2009. Production of infectious genotype 1b virus particles in cell culture and impairment by replication enhancing mutations. PLoS Pathog. 5:e1000475.
58. Rai, R., and J. Deval. 1 February 2011. New opportunities in anti-hepatitis C virus drug discovery: targeting NS4B. Antiviral Res. doi:10.1016/j.antiviral. 2011.01.009.
59. Russell, R. S., et al. 2008. Advantages of a single-cycle production assay to study cell culture-adaptive mutations of hepatitis C virus. Proc. Natl. Acad. Sci. U. S. A. 105:4370-4375.
60. Sali, A. 1995. Comparative protein modeling by satisfaction of spatial restraints. Mol. Med. Today 1:270-277.
61. Sali, A. 1995. Modeling mutations and homologous proteins. Curr. Opin. Biotechnol. 6:437-451.
62. Sali, A., L. Potterton, F. Yuan, H. van Vlijmen, and M. Karplus. 1995. Evaluation of comparative protein modeling by MODELLER. Proteins 23: 318-326.
63. Simmonds, P., et al. 2005. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 42:962-973.
64. Smith, S. O., et al. 2001. Structure of the transmembrane dimer interface of glycophorin A in membrane bilayers. Biochemistry 40:6553-6558.
65. Stone, M., S. Jia, W. D. Heo, T. Meyer, and K. V. Konan. 2007. Participation of Rab5, an early endosome protein, in hepatitis C virus RNA replication machinery. J. Virol. 81:4551-4563.
66. Tackett, A. J., L. Wei, C. E. Cameron, and K. D. Raney. 2001. Unwinding of nucleic acids by HCV NS3 helicase is sensitive to the structure of the duplex. Nucleic Acids Res. 29:565-572.
67. Targett-Adams, P., S. Boulant, and J. McLauchlan. 2008. Visualization of double-stranded RNA in cells supporting hepatitis C virus RNA replication. J. Virol. 82:2182-2195.
68. Targett-Adams, P., and J. McLauchlan. 2005. Development and characterization of a transient-replication assay for the genotype 2a hepatitis C virus subgenomic replicon. J. Gen. Virol. 86:3075-3080.
69. Tellinghuisen, T. L., K. L. Foss, and J. Treadaway. 2008. Regulation of hepatitis C virion production via phosphorylation of the NS5A protein. PLoS Pathog. 4:e1000032.
70. Thompson, A. A., et al. 2009. Biochemical characterization of recombinant hepatitis C virus nonstructural protein 4B: evidence for ATP/GTP hydrolysis and adenylate kinase activity. Biochemistry 48:906-916.
71. Wakita, T., et al. 2005. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med. 11:791-796.
72. Wölk, B., et al. 2000. Subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus NS3-NS4A complex expressed in tetracycline-regulated cell lines. J. Virol. 74:2293-2304.
73. Yi, M., Y. Ma, J. Yates, and S. M. Lemon. 2007. Compensatory mutations in E1, p7, NS2, and NS3 enhance yields of cell culture-infectious intergenotypic chimeric hepatitis C virus. J. Virol. 81:629-638.
74. Yu, G. Y., K. J. Lee, L. Gao, and M. M. Lai. 2006. Palmitoylation and polymerization of hepatitis C virus NS4B protein. J. Virol. 80:6013-6023.
75. Zhong, J., et al. 2005. Robust hepatitis C virus infection in vitro. Proc. Natl. Acad. Sci. U. S. A. 102:9294-9299.
76. Zhong, J., et al. 2006. Persistent hepatitis C virus infection in vitro: coevolution of virus and host. J. Virol. 80:11082-11093.
77. Zhu, J., et al. 2009. The structure of a receptor with two associating transmembrane domains on the cell surface: integrin IIb 3. Mol. Cell 34:234-249.