Abstract
Hepatitis C virus (HCV) variability was analyzed based upon an isolate which had caused the infection of more than 2500 women in 1978/79. Genome consensus sequences of two isolates obtained from the infectious source (HCV-AD78) and from a chronic hepatitis patient 10 years after the acute infection were determined. The entire open reading frame (ORF) exhibited 3.2 × 10-3 nucleotide substitutions per site per year (Δnt). Core (0.7 × 10-3 Δnt) and NS5B (1.9 × 10-3 Δnt) were found to be most conserved genes, while E2 (4.7 × 10-3 Δnt) with hypervariable region 1 (HVR1) (23 × 10-3 Δnt) was the most variable followed by p7 (4.2 × 10-3 Δnt). In the entire ORF transitions were 4.5 times more frequent than transversions while for the HVR1 this bias was turned. As an indicator of relative selective pressure on the proteins the rates of nonsynonymous to synonymous substitutions (dN/dS) were determined. The obtained values exceeded 1.0 only for E2 (dN/dS=1.3). A subdivision of the entire ORF into 88 overlapping sections, each containing 300 nucleotides, led to a more precise analysis of HCV diversity. Besides for E2 an increased variability was mainly detected for three other regions: (a) the C terminal neighbouring region of E2 including p7, (b) the genome fragment extending from approximately the middle of NS3 to NS4B, and (c) the segment corresponding to the C-terminus of the NS5A protein. The variable region in NS5A was situated carboxyterminal to the predicted interferon sensitivity determining region (ISDR). These results suggest which regions other than HVR1 might contribute to persistence of the virus by the mechanism of immunescape.
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References
World Health Organization, Wkly Epidemiol Rec 72, 65–72, 1997.
Alter H.J., Blood 85, 1681–1695, 1995.
Di Bisceglie A.M., Lancet 351, 351–355, 1998.
Houghton M., in Fields B.N., Knipe D.M., Howley P.M. (eds). Fields Virology, Volume 1, Lippincott-Raven, Philadelphia, New York, 1996, pp. 931–960.
Wang C., Sarnow P., and Siddiqui A., J Virol 68, 7301–7307, 1994.
Yanagi M., St Claire M., Emerson S.U., Purcell R.H., and Bukh J., Proc Natl Acad Sci USA 96, 2291–2295, 1999.
Lin C., Lindenbach B.D., Pragai B.M., McCourt D.W., and Rice C.M., J Virol 68, 5063–5073, 1994.
Simmonds P., Smith D.B., McOmish F., Yap P.L., Kolberg J., Urdea M.S., and Holmes E.C., J Gen Virol 75, 1053–1061, 1994.
Robertson B., Myers G., Howard C., Brettin T., Bukh J., Gaschen B., Gojobori T., Maertens G., Mizokami M., Nainan O., Netesov S., Nishioka K., Shini T., Simmonds P., Smith D., Stuyver L., and Weiner A., Arch Virol 143, 2493–2503, 1998.
Smith D.B. and Simmonds P., J Mol Evol 45, 238–246, 1997.
Kato N., Ootsuyama Y., Tanaka T., Nakagawa M., Nakazawa T., Muraiso K., Ohkoshi S., Hijikata M., and Shimotohno K., Virus Res 22, 107–123, 1992.
Martell M., Esteban J.I., Quer J., Genesca J., Weiner A., Esteban R., Guardia J., and Gomez J., J Virol 66, 3225–3229, 1992.
Behrens S.E., Tomei L., and De Francesco R., EMBO J 15, 12–22, 1996.
Lohmann V., Korner F., Herian U., and Bartenschlager R., J Virol 71, 8416–8428, 1997.
Neumann A.U., Lam N.P., Dahari H., Gretch D.R., Wiley T.E., Layden T.J., and Perelson A.S., Science 282, 103–107, 1998.
Enomoto N., Sakuma I., Asahina Y., Kurosaki M., Murakami T., Yamamoto C., Ogura Y., Izumi N., Marumo F., and Sato C., N Engl J Med 334, 77–81, 1996.
Weiner A.J., Geysen H.M., Christopherson C., Hall J.E., Mason T.J., Saracco G., Bonino F., Crawford K., Marion C.D., and Crawford K.A., Proc Natl Acad Sci USA 89, 3468–3472, 1992.
van Doorn L.J., Capriles I., Maertens G., DeLeys R., Murray K., Kos T., Schellekens H., and Quint W., J Virol 69, 773–778, 1995.
Brambilla S., Bellati G., Asti M., Lisa A., Candusso M.E., D'Amico M., Grassi G., Giacca M., Franchini A., Bruno S., Ideo G., Mondelli M.U., and Silini E.M., Hepatology 27, 1678–1686, 1998.
Bassett S.E., Thomas D.L., Brasky K.M., and Lanford R.E., J Virol 73, 1118–1126, 1999.
Major M.E., Mihalik K., Fernandez J., Seidman J., Kleiner D., Kolykhalov A.A., Rice C.M., and Feinstone S.M., J Virol 73, 3317–3325, 1999.
Meisel H., Reip A., Faltus B., Lu M., Porst H., Wiese M., Roggendorf M., and Kruger D.H., Lancet 345, 1209–1211, 1995.
Power J.P., Lawlor E., Davidson F., Holmes E.C., Yap P.L., and Simmonds P., Lancet 345, 1211–1213, 1995.
Wiese M., in NonA-nonB-Hepatitis, Virushepatitis C: Forschung und Praxis, Gustav Fischer Verlag, Jena, 1991, pp. 126–157.
Zibert A., Schreier E., and Roggendorf M., Virology 208, 653–661, 1995.
Rispeter K., Lu M., Lechner S., Zibert A., and Roggendorf M., J Gen Virol 78, 2751–2759, 1997.
Smith D.B., McAllister J., Casino C., and Simmonds P., J Gen Virol 78, 1511–1519, 1997.
Ogata N., Alter H.J., Miller R.H., and Purcell R.H., Proc Natl Acad Sci USA 88, 3392–3396, 1991.
Hwang S.S., Boyle T.J., Lyerly H.K., and Cullen B.R., Science 253, 71–74, 1991.
Zhang L.Q., MacKenzie P., Cleland A., Holmes E.C., Brown A.J., and Simmonds P., J Virol 67, 3345–3356, 1993.
Tabatabai N.M., Bian T.H., Rice C.M., Yoshizawa, Gill J., and Eckels D.D., Hum Immunol 60, 105–115, 1999.
Wang H. and Eckels D.D., J Immunol 162, 4177–4183, 1999.
Gale M. Jr., Blakely C.M., Kwieciszewski B., Tan S.L., Dossett M., Tang N.M., Korth M.J., Polyak S.J., Gretch D.R., and Katze M.G., Mol Cell Biol 18, 5208–5218, 1998.
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Rispeter, K., Lu, M., Behrens, SE. et al. Hepatitis C Virus Variability: Sequence Analysis of an Isolate after 10 Years of Chronic Infection. Virus Genes 21, 179–188 (2000). https://doi.org/10.1023/A:1008135413215
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DOI: https://doi.org/10.1023/A:1008135413215