• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. May 1992; 66(5): 3225–3229.
PMCID: PMC241092

Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution.

Abstract

Sequencing of multiple recombinant clones generated from polymerase chain reaction-amplified products demonstrated that the degree of heterogeneity of two well-conserved regions of the hepatitis C virus (HCV) genome within individual plasma samples from a single patient was consistent with a quasispecies structure of HCV genomic RNA. About half of circulating RNA molecules were identical, while the remaining consisted of a spectrum of mutants differing from each other in one to four nucleotides. Mutant sequence diversity ranged from silent mutations to appearance of in-frame stop codons and included both conservative and nonconservative amino acid substitutions. From the relative proportion of essentially defective sequences, we estimated that most circulating particles should contain defective genomes. These observations might have important implications in the physiopathology of HCV infection and underline the need for a population-based approach when one is analyzing HCV genomes.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (806K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alter HJ, Purcell RH, Shih JW, Melpolder JC, Houghton M, Choo QL, Kuo G. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med. 1989 Nov 30;321(22):1494–1500. [PubMed]
  • Barrett AD, Dimmock NJ. Defective interfering viruses and infections of animals. Curr Top Microbiol Immunol. 1986;128:55–84. [PubMed]
  • Batschelet E, Domingo E, Weissmann C. The proportion of revertant and mutant phage in a growing population, as a function of mutation and growth rate. Gene. 1976;1(1):27–32. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359–362. [PubMed]
  • Choo QL, Richman KH, Han JH, Berger K, Lee C, Dong C, Gallegos C, Coit D, Medina-Selby R, Barr PJ, et al. Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2451–2455. [PMC free article] [PubMed]
  • Domingo E. RNA virus evolution and the control of viral disease. Prog Drug Res. 1989;33:93–133. [PubMed]
  • Domingo E, Sabo D, Taniguchi T, Weissmann C. Nucleotide sequence heterogeneity of an RNA phage population. Cell. 1978 Apr;13(4):735–744. [PubMed]
  • Esteban JI, Esteban R, Viladomiu L, López-Talavera JC, González A, Hernández JM, Roget M, Vargas V, Genescà J, Buti M, et al. Hepatitis C virus antibodies among risk groups in Spain. Lancet. 1989 Aug 5;2(8658):294–297. [PubMed]
  • Evans DM, Dunn G, Minor PD, Schild GC, Cann AJ, Stanway G, Almond JW, Currey K, Maizel JV., Jr Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. Nature. 1985 Apr 11;314(6011):548–550. [PubMed]
  • Han JH, Shyamala V, Richman KH, Brauer MJ, Irvine B, Urdea MS, Tekamp-Olson P, Kuo G, Choo QL, Houghton M. Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1711–1715. [PMC free article] [PubMed]
  • Holland JJ, de la Torre JC, Clarke DK, Duarte E. Quantitation of relative fitness and great adaptability of clonal populations of RNA viruses. J Virol. 1991 Jun;65(6):2960–2967. [PMC free article] [PubMed]
  • Houghton M, Weiner A, Han J, Kuo G, Choo QL. Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease. Hepatology. 1991 Aug;14(2):381–388. [PubMed]
  • Kremsdorf D, Porchon C, Kim JP, Reyes GR, Bréchot C. Partial nucleotide sequence analysis of a French hepatitis C virus: implications for HCV genetic variability in the E2/NS1 protein. J Gen Virol. 1991 Oct;72(Pt 10):2557–2561. [PubMed]
  • Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989 Apr 21;244(4902):362–364. [PubMed]
  • Martínez MA, Carrillo C, González-Candelas F, Moya A, Domingo E, Sobrino F. Fitness alteration of foot-and-mouth disease virus mutants: measurement of adaptability of viral quasispecies. J Virol. 1991 Jul;65(7):3954–3957. [PMC free article] [PubMed]
  • Mateu MG, Martínez MA, Rocha E, Andreu D, Parejo J, Giralt E, Sobrino F, Domingo E. Implications of a quasispecies genome structure: effect of frequent, naturally occurring amino acid substitutions on the antigenicity of foot-and-mouth disease virus. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5883–5887. [PMC free article] [PubMed]
  • Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. [PMC free article] [PubMed]
  • Meyerhans A, Cheynier R, Albert J, Seth M, Kwok S, Sninsky J, Morfeldt-Månson L, Asjö B, Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. [PubMed]
  • Miller RH, Purcell RH. 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 Mar;87(6):2057–2061. [PMC free article] [PubMed]
  • Ogata N, Alter HJ, Miller RH, Purcell RH. Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3392–3396. [PMC free article] [PubMed]
  • Parry N, Fox G, Rowlands D, Brown F, Fry E, Acharya R, Logan D, Stuart D. Structural and serological evidence for a novel mechanism of antigenic variation in foot-and-mouth disease virus. Nature. 1990 Oct 11;347(6293):569–572. [PubMed]
  • Remington KM, Chesebro B, Wehrly K, Pedersen NC, North TW. Mutants of feline immunodeficiency virus resistant to 3'-azido-3'-deoxythymidine. J Virol. 1991 Jan;65(1):308–312. [PMC free article] [PubMed]
  • Salvato M, Borrow P, Shimomaye E, Oldstone MB. Molecular basis of viral persistence: a single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with suppression of the antiviral cytotoxic T-lymphocyte response and establishment of persistence. J Virol. 1991 Apr;65(4):1863–1869. [PMC free article] [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Steinhauer DA, Holland JJ. Rapid evolution of RNA viruses. Annu Rev Microbiol. 1987;41:409–433. [PubMed]
  • Takamizawa A, Mori C, Fuke I, Manabe S, Murakami S, Fujita J, Onishi E, Andoh T, Yoshida I, Okayama H. Structure and organization of the hepatitis C virus genome isolated from human carriers. J Virol. 1991 Mar;65(3):1105–1113. [PMC free article] [PubMed]
  • Takeuchi K, Kubo Y, Boonmar S, Watanabe Y, Katayama T, Choo QL, Kuo G, Houghton M, Saito I, Miyamura T. The putative nucleocapsid and envelope protein genes of hepatitis C virus determined by comparison of the nucleotide sequences of two isolates derived from an experimentally infected chimpanzee and healthy human carriers. J Gen Virol. 1990 Dec;71(Pt 12):3027–3033. [PubMed]
  • Weiner AJ, Brauer MJ, Rosenblatt J, Richman KH, Tung J, Crawford K, Bonino F, Saracco G, Choo QL, Houghton M, et al. Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology. 1991 Feb;180(2):842–848. [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...