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

Overview

Journal Virus Genes

Specialties Microbiology
Molecular Biology

Date 1992 Apr 1

PMID 1589964

Citations 10

Authors

K E FRY

A W Tam

M M Smith

J P Kim

K C Luk

L M Young

M Piatak

R A Feldman

K Y Yun

M A Purdy

Affiliations

Soon will be listed here.

Abstract

Hepatitis is transmitted by a number of infectious agents. The epidemiological characterization of waterborne or enterically transmitted non-A, non-B hepatitis (ET-NANBH) is unique when compared with other known hepatitides. We have reported on the molecular cloning of a cDNA clone derived from the etiologic agent associated with ET-NANBH, the hepatitis E virus (HEV). The complete sequence of these first molecular clones, isolated from an HEV-infected human after passage in Macaca fascicularis (cynomolgus macaques), illustrates a distant relationship to other known positive-strand RNA viruses of plants and animals. The translated major open reading frame (ORF-1) from these clones indicates that this portion of the genome encodes a polyprotein with consensus sequences found in RNA-dependent RNA polymerase and ATP/GTP binding domains. The latter activity has been associated with putative helicases of positive-strand RNA viruses. These viral-encoded enzymatic activities identify this region and ORF-1 as containing at least two different nonstructural genes involved in HEV replication. Molecular clones obtained from two other geographically distinct HEV isolates demonstrated sequence heterogeneity in this nonstructural gene region. Further study will be required to elucidate the pathogenic significance (if any) of this observed divergence in the nonstructural region.

Citing Articles

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High variety of known and new RNA and DNA viruses of diverse origins in untreated sewage.

Ng T, Marine R, Wang C, Simmonds P, Kapusinszky B, Bodhidatta L J Virol. 2012; 86(22):12161-75.

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The ORF3 protein of hepatitis E virus is a phosphoprotein that associates with the cytoskeleton.

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References

Viswanathan R . Epidemiology. Indian J Med Res. 1957; 45(Suppl.):1-29. View

Gravelle C, Hornbeck C, MAYNARD J, Schable C, Cook E, Bradley D . Hepatitis A: report of a common-source outbreak with recovery of a possible etiologic agent. II. Laboratory studies. J Infect Dis. 1975; 131(2):167-71. DOI: 10.1093/infdis/131.2.167. View

McLachlan A . Repeating sequences and gene duplication in proteins. J Mol Biol. 1972; 64(2):417-37. DOI: 10.1016/0022-2836(72)90508-6. View

Pearson W, Lipman D . Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988; 85(8):2444-8. PMC: 280013. DOI: 10.1073/pnas.85.8.2444. View

De Cock K, Bradley D, Sandford N, Govindarajan S, MAYNARD J, Redeker A . Epidemic non-A, non-B hepatitis in patients from Pakistan. Ann Intern Med. 1987; 106(2):227-30. DOI: 10.7326/0003-4819-106-2-227. View

Frey T, Marr L . Sequence of the region coding for virion proteins C and E2 and the carboxy terminus of the nonstructural proteins of rubella virus: comparison with alphaviruses. Gene. 1988; 62(1):85-99. DOI: 10.1016/0378-1119(88)90582-3. View

Wong D, Purcell R, Sreenivasan M, Prasad S, Pavri K . Epidemic and endemic hepatitis in India: evidence for a non-A, non-B hepatitis virus aetiology. Lancet. 1980; 2(8200):876-9. DOI: 10.1016/s0140-6736(80)92045-0. View

Higgins D, Sharp P . Fast and sensitive multiple sequence alignments on a microcomputer. Comput Appl Biosci. 1989; 5(2):151-3. DOI: 10.1093/bioinformatics/5.2.151. View

Walker J, Saraste M, Runswick M, Gay N . Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1982; 1(8):945-51. PMC: 553140. DOI: 10.1002/j.1460-2075.1982.tb01276.x. View

10.

Miller R, Purcell R . 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. 1990; 87(6):2057-61. PMC: 53625. DOI: 10.1073/pnas.87.6.2057. View

11.

Bradley D, MAYNARD J . Etiology and natural history of post-transfusion and enterically-transmitted non-A, non-B hepatitis. Semin Liver Dis. 1986; 6(1):56-66. DOI: 10.1055/s-2008-1040794. View

12.

Kamer G, Argos P . Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses. Nucleic Acids Res. 1984; 12(18):7269-82. PMC: 320156. DOI: 10.1093/nar/12.18.7269. View

13.

Brutlag D, Dautricourt J, Maulik S, Relph J . Improved sensitivity of biological sequence database searches. Comput Appl Biosci. 1990; 6(3):237-45. DOI: 10.1093/bioinformatics/6.3.237. View

14.

Dever T, Glynias M, Merrick W . GTP-binding domain: three consensus sequence elements with distinct spacing. Proc Natl Acad Sci U S A. 1987; 84(7):1814-8. PMC: 304531. DOI: 10.1073/pnas.84.7.1814. View

15.

Bradley D, Krawczynski K, Cook Jr E, McCaustland K, Humphrey C, Spelbring J . 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; 84(17):6277-81. PMC: 299054. DOI: 10.1073/pnas.84.17.6277. View

16.

Reyes G, Purdy M, Kim J, Luk K, Young L, FRY K . Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science. 1990; 247(4948):1335-9. DOI: 10.1126/science.2107574. View

17.

SANGER F, Nicklen S, Coulson A . DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977; 74(12):5463-7. PMC: 431765. DOI: 10.1073/pnas.74.12.5463. View

18.

Bradley D, Andjaparidze A, Cook Jr E, McCaustland K, Balayan M, Stetler H . Aetiological agent of enterically transmitted non-A, non-B hepatitis. J Gen Virol. 1988; 69 ( Pt 3):731-8. DOI: 10.1099/0022-1317-69-3-731. View

19.

Neill J . 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; 17(3):145-60. DOI: 10.1016/0168-1702(90)90061-f. View

20.

Gorbalenya A, Koonin E, Donchenko A, Blinov V . Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res. 1989; 17(12):4713-30. PMC: 318027. DOI: 10.1093/nar/17.12.4713. View