Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Sep 1;89(17):8259–8263. doi: 10.1073/pnas.89.17.8259

Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive-strand RNA plant and animal viruses.

E V Koonin 1, A E Gorbalenya 1, M A Purdy 1, M N Rozanov 1, G R Reyes 1, D W Bradley 1
PMCID: PMC49897  PMID: 1518855

Abstract

Computer-assisted comparison of the nonstructural polyprotein of hepatitis E virus (HEV) with proteins of other positive-strand RNA viruses allowed the identification of the following putative functional domains: (i) RNA-dependent RNA polymerase, (ii) RNA helicase, (iii) methyltransferase, (iv) a domain of unknown function ("X" domain) flanking the papain-like protease domains in the polyproteins of animal positive-strand RNA viruses, and (v) papain-like cysteine protease domain distantly related to the putative papain-like protease of rubella virus (RubV). Comparative analysis of the polymerase and helicase sequences of positive-strand RNA viruses belonging to the so-called "alpha-like" supergroup revealed grouping between HEV, RubV, and beet necrotic yellow vein virus (BNYVV), a plant furovirus. Two additional domains have been identified: one showed significant conservation between HEV, RubV, and BNYVV, and the other showed conservation specifically between HEV and RubV. The large nonstructural proteins of HEV, RubV, and BNYVV retained similar domain organization, with the exceptions of relocation of the putative protease domain in HEV as compared to RubV and the absence of the protease and X domains in BNYVV. These observations show that HEV, RubV, and BNYVV encompass partially conserved arrays of distinctive putative functional domains, suggesting that these viruses constitute a distinct monophyletic group within the alpha-like supergroup of positive-strand RNA viruses.

Full text

PDF
8259

Images in this article

8263Image
on p.8263

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradley D. W., Krawczynski K., Cook E. H., Jr, McCaustland K. A., Humphrey C. D., Spelbring J. E., Myint H., Maynard J. E. Enterically transmitted non-A, non-B hepatitis: serial passage of disease in cynomolgus macaques and tamarins and recovery of disease-associated 27- to 34-nm viruslike particles. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6277–6281. doi: 10.1073/pnas.84.17.6277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradley D. W., Maynard J. E. Etiology and natural history of post-transfusion and enterically-transmitted non-A, non-B hepatitis. Semin Liver Dis. 1986 Feb;6(1):56–66. doi: 10.1055/s-2008-1040794. [DOI] [PubMed] [Google Scholar]
  3. Dominguez G., Wang C. Y., Frey T. K. Sequence of the genome RNA of rubella virus: evidence for genetic rearrangement during togavirus evolution. Virology. 1990 Jul;177(1):225–238. doi: 10.1016/0042-6822(90)90476-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fry K. E., Tam A. W., Smith M. M., Kim J. P., Luk K. C., Young L. M., Piatak M., Feldman R. A., Yun K. Y., Purdy M. A. Hepatitis E virus (HEV): strain variation in the nonstructural gene region encoding consensus motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site. Virus Genes. 1992 Apr;6(2):173–185. doi: 10.1007/BF01703066. [DOI] [PubMed] [Google Scholar]
  5. Goldbach R., Wellink J. Evolution of plus-strand RNA viruses. Intervirology. 1988;29(5):260–267. doi: 10.1159/000150054. [DOI] [PubMed] [Google Scholar]
  6. Gorbalenya A. E., Blinov V. M., Donchenko A. P., Koonin E. V. An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication. J Mol Evol. 1989 Mar;28(3):256–268. doi: 10.1007/BF02102483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gorbalenya A. E., Donchenko A. P., Blinov V. M., Koonin E. V. Cysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases. A distinct protein superfamily with a common structural fold. FEBS Lett. 1989 Jan 30;243(2):103–114. doi: 10.1016/0014-5793(89)80109-7. [DOI] [PubMed] [Google Scholar]
  8. Gorbalenya A. E., Donchenko A. P., Koonin E. V., Blinov V. M. N-terminal domains of putative helicases of flavi- and pestiviruses may be serine proteases. Nucleic Acids Res. 1989 May 25;17(10):3889–3897. doi: 10.1093/nar/17.10.3889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gorbalenya A. E., Koonin E. V., Donchenko A. P., Blinov V. M. A novel superfamily of nucleoside triphosphate-binding motif containing proteins which are probably involved in duplex unwinding in DNA and RNA replication and recombination. FEBS Lett. 1988 Aug 1;235(1-2):16–24. doi: 10.1016/0014-5793(88)81226-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gorbalenya A. E., Koonin E. V., Donchenko A. P., Blinov V. M. Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res. 1989 Jun 26;17(12):4713–4730. doi: 10.1093/nar/17.12.4713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gorbalenya A. E., Koonin E. V., Lai M. M. Putative papain-related thiol proteases of positive-strand RNA viruses. Identification of rubi- and aphthovirus proteases and delineation of a novel conserved domain associated with proteases of rubi-, alpha- and coronaviruses. FEBS Lett. 1991 Aug 19;288(1-2):201–205. doi: 10.1016/0014-5793(91)81034-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hardy W. R., Strauss J. H. Processing the nonstructural polyproteins of sindbis virus: nonstructural proteinase is in the C-terminal half of nsP2 and functions both in cis and in trans. J Virol. 1989 Nov;63(11):4653–4664. doi: 10.1128/jvi.63.11.4653-4664.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koonin E. V. The phylogeny of RNA-dependent RNA polymerases of positive-strand RNA viruses. J Gen Virol. 1991 Sep;72(Pt 9):2197–2206. doi: 10.1099/0022-1317-72-9-2197. [DOI] [PubMed] [Google Scholar]
  14. Krawczynski K., Bradley D. W. Enterically transmitted non-A, non-B hepatitis: identification of virus-associated antigen in experimentally infected cynomolgus macaques. J Infect Dis. 1989 Jun;159(6):1042–1049. doi: 10.1093/infdis/159.6.1042. [DOI] [PubMed] [Google Scholar]
  15. Kräusslich H. G., Wimmer E. Viral proteinases. Annu Rev Biochem. 1988;57:701–754. doi: 10.1146/annurev.bi.57.070188.003413. [DOI] [PubMed] [Google Scholar]
  16. Mi S., Durbin R., Huang H. V., Rice C. M., Stollar V. Association of the Sindbis virus RNA methyltransferase activity with the nonstructural protein nsP1. Virology. 1989 Jun;170(2):385–391. doi: 10.1016/0042-6822(89)90429-7. [DOI] [PubMed] [Google Scholar]
  17. Mi S., Stollar V. Expression of Sindbis virus nsP1 and methyltransferase activity in Escherichia coli. Virology. 1991 Sep;184(1):423–427. doi: 10.1016/0042-6822(91)90862-6. [DOI] [PubMed] [Google Scholar]
  18. Morozov SYu, Dolja V. V., Atabekov J. G. Probable reassortment of genomic elements among elongated RNA-containing plant viruses. J Mol Evol. 1989 Jul;29(1):52–62. doi: 10.1007/BF02106181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Neill J. D. Nucleotide sequence of a region of the feline calicivirus genome which encodes picornavirus-like RNA-dependent RNA polymerase, cysteine protease and 2C polypeptides. Virus Res. 1990 Nov;17(3):145–160. doi: 10.1016/0168-1702(90)90061-f. [DOI] [PubMed] [Google Scholar]
  20. Reyes G. R., Purdy M. A., Kim J. P., Luk K. C., Young L. M., Fry K. E., Bradley D. W. Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science. 1990 Mar 16;247(4948):1335–1339. doi: 10.1126/science.2107574. [DOI] [PubMed] [Google Scholar]
  21. Scheidel L. M., Stollar V. Mutations that confer resistance to mycophenolic acid and ribavirin on Sindbis virus map to the nonstructural protein nsP1. Virology. 1991 Apr;181(2):490–499. doi: 10.1016/0042-6822(91)90881-b. [DOI] [PubMed] [Google Scholar]
  22. Strauss E. G., Rice C. M., Strauss J. H. Complete nucleotide sequence of the genomic RNA of Sindbis virus. Virology. 1984 Feb;133(1):92–110. doi: 10.1016/0042-6822(84)90428-8. [DOI] [PubMed] [Google Scholar]
  23. Tam A. W., Smith M. M., Guerra M. E., Huang C. C., Bradley D. W., Fry K. E., Reyes G. R. Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology. 1991 Nov;185(1):120–131. doi: 10.1016/0042-6822(91)90760-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yarbough P. O., Tam A. W., Fry K. E., Krawczynski K., McCaustland K. A., Bradley D. W., Reyes G. R. Hepatitis E virus: identification of type-common epitopes. J Virol. 1991 Nov;65(11):5790–5797. doi: 10.1128/jvi.65.11.5790-5797.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. den Boon J. A., Snijder E. J., Chirnside E. D., de Vries A. A., Horzinek M. C., Spaan W. J. Equine arteritis virus is not a togavirus but belongs to the coronaviruslike superfamily. J Virol. 1991 Jun;65(6):2910–2920. doi: 10.1128/jvi.65.6.2910-2920.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES