• 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 1993; 67(5): 2832–2843.
PMCID: PMC237608

Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites.

Abstract

Processing of the hepatitis C virus (HCV) H strain polyprotein yields at least nine distinct cleavage products: NH2-C-E1-E2-NS2-NS3-NS4A-NS4B-NS5A-NS5B-CO OH. As described in this report, site-directed mutagenesis and transient expression analyses were used to study the role of a putative serine proteinase domain, located in the N-terminal one-third of the NS3 protein, in proteolytic processing of HCV polyproteins. All four cleavages which occur C terminal to the proteinase domain (3/4A, 4A/4B, 4B/5A, and 5A/5B) were abolished by substitution of alanine for either of two predicted residues (His-1083 and Ser-1165) in the proteinase catalytic triad. However, such substitutions have no observable effect on cleavages in the structural region or at the 2/3 site. Deletion analyses suggest that the structural and NS2 regions of the polyprotein are not required for the HCV NS3 proteinase activity. NS3 proteinase-dependent cleavage sites were localized by N-terminal sequence analysis of NS4A, NS4B, NS5A, and NS5B. Sequence comparison of the residues flanking these cleavage sites for all sequenced HCV strains reveals conserved residues which may play a role in determining HCV NS3 proteinase substrate specificity. These features include an acidic residue (Asp or Glu) at the P6 position, a Cys or Thr residue at the P1 position, and a Ser or Ala residue at the P1' position.

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 (2.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alter HJ, Purcell RH, Holland PV, Popper H. Transmissible agent in non-A, non-B hepatitis. Lancet. 1978 Mar 4;1(8062):459–463. [PubMed]
  • 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]
  • Alter MJ, Hadler SC, Judson FN, Mares A, Alexander WJ, Hu PY, Miller JK, Moyer LA, Fields HA, Bradley DW, et al. Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. JAMA. 1990 Nov 7;264(17):2231–2235. [PubMed]
  • Bazan JF, Fletterick RJ. Detection of a trypsin-like serine protease domain in flaviviruses and pestiviruses. Virology. 1989 Aug;171(2):637–639. [PubMed]
  • Bradley DW, Maynard JE, Popper H, Cook EH, Ebert JW, McCaustland KA, Schable CA, Fields HA. Posttransfusion non-A, non-B hepatitis: physicochemical properties of two distinct agents. J Infect Dis. 1983 Aug;148(2):254–265. [PubMed]
  • Bruix J, Barrera JM, Calvet X, Ercilla G, Costa J, Sanchez-Tapias JM, Ventura M, Vall M, Bruguera M, Bru C, et al. Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and hepatic cirrhosis. Lancet. 1989 Oct 28;2(8670):1004–1006. [PubMed]
  • Cahour A, Falgout B, Lai CJ. Cleavage of the dengue virus polyprotein at the NS3/NS4A and NS4B/NS5 junctions is mediated by viral protease NS2B-NS3, whereas NS4A/NS4B may be processed by a cellular protease. J Virol. 1992 Mar;66(3):1535–1542. [PMC free article] [PubMed]
  • Chambers TJ, Grakoui A, Rice CM. Processing of the yellow fever virus nonstructural polyprotein: a catalytically active NS3 proteinase domain and NS2B are required for cleavages at dibasic sites. J Virol. 1991 Nov;65(11):6042–6050. [PMC free article] [PubMed]
  • Chambers TJ, Hahn CS, Galler R, Rice CM. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol. 1990;44:649–688. [PubMed]
  • Chambers TJ, McCourt DW, Rice CM. Yellow fever virus proteins NS2A, NS2B, and NS4B: identification and partial N-terminal amino acid sequence analysis. Virology. 1989 Mar;169(1):100–109. [PubMed]
  • Chambers TJ, Weir RC, Grakoui A, McCourt DW, Bazan JF, Fletterick RJ, Rice CM. Evidence that the N-terminal domain of nonstructural protein NS3 from yellow fever virus is a serine protease responsible for site-specific cleavages in the viral polyprotein. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8898–8902. [PMC free article] [PubMed]
  • Chen PJ, Lin MH, Tai KF, Liu PC, Lin CJ, Chen DS. The Taiwanese hepatitis C virus genome: sequence determination and mapping the 5' termini of viral genomic and antigenomic RNA. Virology. 1992 May;188(1):102–113. [PubMed]
  • Chiba J, Ohba H, Matsuura Y, Watanabe Y, Katayama T, Kikuchi S, Saito I, Miyamura T. Serodiagnosis of hepatitis C virus (HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4641–4645. [PMC free article] [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]
  • Collett MS. Molecular genetics of pestiviruses. Comp Immunol Microbiol Infect Dis. 1992 Jul;15(3):145–154. [PubMed]
  • Colett MS, Larson R, Gold C, Strick D, Anderson DK, Purchio AF. Molecular cloning and nucleotide sequence of the pestivirus bovine viral diarrhea virus. Virology. 1988 Jul;165(1):191–199. [PubMed]
  • Collett MS, Wiskerchen M, Welniak E, Belzer SK. Bovine viral diarrhea virus genomic organization. Arch Virol Suppl. 1991;3:19–27. [PubMed]
  • Colombo M, Kuo G, Choo QL, Donato MF, Del Ninno E, Tommasini MA, Dioguardi N, Houghton M. Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet. 1989 Oct 28;2(8670):1006–1008. [PubMed]
  • Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC, Jr, Perrillo RP, Carey W, Jacobson IM, Payne J, Dienstag JL, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med. 1989 Nov 30;321(22):1501–1506. [PubMed]
  • Di Bisceglie AM, Martin P, Kassianides C, Lisker-Melman M, Murray L, Waggoner J, Goodman Z, Banks SM, Hoofnagle JH. Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N Engl J Med. 1989 Nov 30;321(22):1506–1510. [PubMed]
  • Elroy-Stein O, Fuerst TR, Moss B. Cap-independent translation of mRNA conferred by encephalomyocarditis virus 5' sequence improves the performance of the vaccinia virus/bacteriophage T7 hybrid expression system. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6126–6130. [PMC free article] [PubMed]
  • Falgout B, Pethel M, Zhang YM, Lai CJ. Both nonstructural proteins NS2B and NS3 are required for the proteolytic processing of dengue virus nonstructural proteins. J Virol. 1991 May;65(5):2467–2475. [PMC free article] [PubMed]
  • Falkner FG, Moss B. Escherichia coli gpt gene provides dominant selection for vaccinia virus open reading frame expression vectors. J Virol. 1988 Jun;62(6):1849–1854. [PMC free article] [PubMed]
  • Farci P, Alter HJ, Govindarajan S, Wong DC, Engle R, Lesniewski RR, Mushahwar IK, Desai SM, Miller RH, Ogata N, et al. Lack of protective immunity against reinfection with hepatitis C virus. Science. 1992 Oct 2;258(5079):135–140. [PubMed]
  • Feinstone SM, Mihalik KB, Kamimura T, Alter HJ, London WT, Purcell RH. Inactivation of hepatitis B virus and non-A, non-B hepatitis by chloroform. Infect Immun. 1983 Aug;41(2):816–821. [PMC free article] [PubMed]
  • Fu J, Tan BH, Yap EH, Chan YC, Tan YH. Full-length cDNA sequence of dengue type 1 virus (Singapore strain S275/90). Virology. 1992 Jun;188(2):953–958. [PubMed]
  • Fuerst TR, Niles EG, Studier FW, Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122–8126. [PMC free article] [PubMed]
  • Gorbalenya AE, Donchenko AP, Koonin EV, Blinov VM. N-terminal domains of putative helicases of flavi- and pestiviruses may be serine proteases. Nucleic Acids Res. 1989 May 25;17(10):3889–3897. [PMC free article] [PubMed]
  • Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM. 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. [PMC free article] [PubMed]
  • Grakoui A, Wychowski C, Lin C, Feinstone SM, Rice CM. Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol. 1993 Mar;67(3):1385–1395. [PMC free article] [PubMed]
  • Hahn CS, Hahn YS, Braciale TJ, Rice CM. Infectious Sindbis virus transient expression vectors for studying antigen processing and presentation. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2679–2683. [PMC free article] [PubMed]
  • Hahn YS, Galler R, Hunkapiller T, Dalrymple JM, Strauss JH, Strauss EG. Nucleotide sequence of dengue 2 RNA and comparison of the encoded proteins with those of other flaviviruses. Virology. 1988 Jan;162(1):167–180. [PubMed]
  • Harada S, Watanabe Y, Takeuchi K, Suzuki T, Katayama T, Takebe Y, Saito I, Miyamura T. Expression of processed core protein of hepatitis C virus in mammalian cells. J Virol. 1991 Jun;65(6):3015–3021. [PMC free article] [PubMed]
  • He LF, Alling D, Popkin T, Shapiro M, Alter HJ, Purcell RH. Determining the size of non-A, non-B hepatitis virus by filtration. J Infect Dis. 1987 Oct;156(4):636–640. [PubMed]
  • Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Shimotohno K. Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5547–5551. [PMC free article] [PubMed]
  • Hollinger FB, Gitnick GL, Aach RD, Szmuness W, Mosley JW, Stevens CE, Peters RL, Weiner JM, Werch JB, Lander JJ. Non-A, non-B hepatitis transmission in chimpanzees: a project of the transfusion-transmitted viruses study group. Intervirology. 1978;10(1):60–68. [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]
  • Hruby DE, Guarino LA, Kates JR. Vaccinia virus replication. I. Requirement for the host-cell nucleus. J Virol. 1979 Feb;29(2):705–715. [PMC free article] [PubMed]
  • Iacono-Connors LC, Schmaljohn CS. Cloning and sequence analysis of the genes encoding the nonstructural proteins of Langat virus and comparative analysis with other flaviviruses. Virology. 1992 Jun;188(2):875–880. [PubMed]
  • Inchauspe G, Zebedee S, Lee DH, Sugitani M, Nasoff M, Prince AM. Genomic structure of the human prototype strain H of hepatitis C virus: comparison with American and Japanese isolates. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10292–10296. [PMC free article] [PubMed]
  • Jacob JR, Burk KH, Eichberg JW, Dreesman GR, Lanford RE. Expression of infectious viral particles by primary chimpanzee hepatocytes isolated during the acute phase of non-A, non-B hepatitis. J Infect Dis. 1990 Jun;161(6):1121–1127. [PubMed]
  • Kato N, Hijikata M, Ootsuyama Y, Nakagawa M, Ohkoshi S, Sugimura T, Shimotohno K. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9524–9528. [PMC free article] [PubMed]
  • Kohara M, Tsukiyama-Kohara K, Maki N, Asano K, Yamaguchi K, Miki K, Tanaka S, Hattori N, Matsuura Y, Saito I, et al. Expression and characterization of glycoprotein gp35 of hepatitis C virus using recombinant vaccinia virus. J Gen Virol. 1992 Sep;73(Pt 9):2313–2318. [PubMed]
  • Kumar U, Cheng D, Thomas H, Monjardino J. Cloning and sequencing of the structural region and expression of putative core gene of hepatitis C virus from a British case of chronic sporadic hepatitis. J Gen Virol. 1992 Jun;73(Pt 6):1521–1525. [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]
  • Lin C, Amberg SM, Chambers TJ, Rice CM. Cleavage at a novel site in the NS4A region by the yellow fever virus NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B signalase site. J Virol. 1993 Apr;67(4):2327–2335. [PMC free article] [PubMed]
  • Lin C, Chambers TJ, Rice CM. Mutagenesis of conserved residues at the yellow fever virus 3/4A and 4B/5 dibasic cleavage sites: effects on cleavage efficiency and polyprotein processing. Virology. 1993 Feb;192(2):596–604. [PubMed]
  • Mackett M, Smith GL. Vaccinia virus expression vectors. J Gen Virol. 1986 Oct;67(Pt 10):2067–2082. [PubMed]
  • Mackow E, Makino Y, Zhao BT, Zhang YM, Markoff L, Buckler-White A, Guiler M, Chanock R, Lai CJ. The nucleotide sequence of dengue type 4 virus: analysis of genes coding for nonstructural proteins. Virology. 1987 Aug;159(2):217–228. [PubMed]
  • Mandl CW, Heinz FX, Stöckl E, Kunz C. Genome sequence of tick-borne encephalitis virus (Western subtype) and comparative analysis of nonstructural proteins with other flaviviruses. Virology. 1989 Nov;173(1):291–301. [PubMed]
  • Matsudaira P. Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J Biol Chem. 1987 Jul 25;262(21):10035–10038. [PubMed]
  • Matsuura Y, Harada S, Suzuki R, Watanabe Y, Inoue Y, Saito I, Miyamura T. Expression of processed envelope protein of hepatitis C virus in mammalian and insect cells. J Virol. 1992 Mar;66(3):1425–1431. [PMC free article] [PubMed]
  • Meyers G, Rümenapf T, Thiel HJ. Molecular cloning and nucleotide sequence of the genome of hog cholera virus. Virology. 1989 Aug;171(2):555–567. [PubMed]
  • Meyers G, Tautz N, Dubovi EJ, Thiel HJ. Viral cytopathogenicity correlated with integration of ubiquitin-coding sequences. Virology. 1991 Feb;180(2):602–616. [PubMed]
  • Meyers G, Tautz N, Stark R, Brownlie J, Dubovi EJ, Collett MS, Thiel HJ. Rearrangement of viral sequences in cytopathogenic pestiviruses. Virology. 1992 Nov;191(1):368–386. [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]
  • Moss B, Elroy-Stein O, Mizukami T, Alexander WA, Fuerst TR. Product review. New mammalian expression vectors. Nature. 1990 Nov 1;348(6296):91–92. [PubMed]
  • Nowak T, Färber PM, Wengler G, Wengler G. Analyses of the terminal sequences of West Nile virus structural proteins and of the in vitro translation of these proteins allow the proposal of a complete scheme of the proteolytic cleavages involved in their synthesis. Virology. 1989 Apr;169(2):365–376. [PubMed]
  • Okamoto H, Kurai K, Okada S, Yamamoto K, Lizuka H, Tanaka T, Fukuda S, Tsuda F, Mishiro S. Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes. Virology. 1992 May;188(1):331–341. [PubMed]
  • Okamoto H, Okada S, Sugiyama Y, Kurai K, Iizuka H, Machida A, Miyakawa Y, Mayumi M. Nucleotide sequence of the genomic RNA of hepatitis C virus isolated from a human carrier: comparison with reported isolates for conserved and divergent regions. J Gen Virol. 1991 Nov;72(Pt 11):2697–2704. [PubMed]
  • Osatomi K, Sumiyoshi H. Complete nucleotide sequence of dengue type 3 virus genome RNA. Virology. 1990 Jun;176(2):643–647. [PubMed]
  • Petric M, Yolken RH, Dubovi EJ, Wiskerchen M, Collett MS. Baculovirus expression of pestivirus non-structural proteins. J Gen Virol. 1992 Jul;73(Pt 7):1867–1871. [PubMed]
  • Poch O, Sauvaget I, Delarue M, Tordo N. Identification of four conserved motifs among the RNA-dependent polymerase encoding elements. EMBO J. 1989 Dec 1;8(12):3867–3874. [PMC free article] [PubMed]
  • Preugschat F, Lenches EM, Strauss JH. Flavivirus enzyme-substrate interactions studied with chimeric proteinases: identification of an intragenic locus important for substrate recognition. J Virol. 1991 Sep;65(9):4749–4758. [PMC free article] [PubMed]
  • Preugschat F, Strauss JH. Processing of nonstructural proteins NS4A and NS4B of dengue 2 virus in vitro and in vivo. Virology. 1991 Dec;185(2):689–697. [PubMed]
  • Preugschat F, Yao CW, Strauss JH. In vitro processing of dengue virus type 2 nonstructural proteins NS2A, NS2B, and NS3. J Virol. 1990 Sep;64(9):4364–4374. [PMC free article] [PubMed]
  • Prince AM, Brotman B, Huima T, Pascual D, Jaffery M, Inchauspé G. Immunity in hepatitis C infection. J Infect Dis. 1992 Mar;165(3):438–443. [PubMed]
  • Rice CM, Lenches EM, Eddy SR, Shin SJ, Sheets RL, Strauss JH. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science. 1985 Aug 23;229(4715):726–733. [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Saito I, Miyamura T, Ohbayashi A, Harada H, Katayama T, Kikuchi S, Watanabe Y, Koi S, Onji M, Ohta Y, et al. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6547–6549. [PMC free article] [PubMed]
  • Shimizu YK, Iwamoto A, Hijikata M, Purcell RH, Yoshikura H. Evidence for in vitro replication of hepatitis C virus genome in a human T-cell line. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5477–5481. [PMC free article] [PubMed]
  • Spaete RR, Alexander D, Rugroden ME, Choo QL, Berger K, Crawford K, Kuo C, Leng S, Lee C, Ralston R, et al. Characterization of the hepatitis C virus E2/NS1 gene product expressed in mammalian cells. Virology. 1992 Jun;188(2):819–830. [PubMed]
  • Speight G, Coia G, Parker MD, Westaway EG. Gene mapping and positive identification of the non-structural proteins NS2A, NS2B, NS3, NS4B and NS5 of the flavivirus Kunjin and their cleavage sites. J Gen Virol. 1988 Jan;69(Pt 1):23–34. [PubMed]
  • Sumiyoshi H, Mori C, Fuke I, Morita K, Kuhara S, Kondou J, Kikuchi Y, Nagamatu H, Igarashi A. Complete nucleotide sequence of the Japanese encephalitis virus genome RNA. Virology. 1987 Dec;161(2):497–510. [PubMed]
  • Tabor E, Gerety RJ, Drucker JA, Seeff LB, Hoofnagle JH, Jackson DR, April M, Barker LF, Pineda-Tamondong G. Transmission of non-A, non-B hepatitis from man to chimpanzee. Lancet. 1978 Mar 4;1(8062):463–466. [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]
  • Tanaka T, Kato N, Nakagawa M, Ootsuyama Y, Cho MJ, Nakazawa T, Hijikata M, Ishimura Y, Shimotohno K. Molecular cloning of hepatitis C virus genome from a single Japanese carrier: sequence variation within the same individual and among infected individuals. Virus Res. 1992 Apr;23(1-2):39–53. [PubMed]
  • Thiel HJ, Stark R, Weiland E, Rümenapf T, Meyers G. Hog cholera virus: molecular composition of virions from a pestivirus. J Virol. 1991 Sep;65(9):4705–4712. [PMC free article] [PubMed]
  • Weiner AJ, Kuo G, Bradley DW, Bonino F, Saracco G, Lee C, Rosenblatt J, Choo QL, Houghton M. Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet. 1990 Jan 6;335(8680):1–3. [PubMed]
  • Wengler G, Czaya G, Färber PM, Hegemann JH. In vitro synthesis of West Nile virus proteins indicates that the amino-terminal segment of the NS3 protein contains the active centre of the protease which cleaves the viral polyprotein after multiple basic amino acids. J Gen Virol. 1991 Apr;72(Pt 4):851–858. [PubMed]
  • Wengler G, Wengler G. The carboxy-terminal part of the NS 3 protein of the West Nile flavivirus can be isolated as a soluble protein after proteolytic cleavage and represents an RNA-stimulated NTPase. Virology. 1991 Oct;184(2):707–715. [PubMed]
  • Wiskerchen M, Belzer SK, Collett MS. Pestivirus gene expression: the first protein product of the bovine viral diarrhea virus large open reading frame, p20, possesses proteolytic activity. J Virol. 1991 Aug;65(8):4508–4514. [PMC free article] [PubMed]
  • Wiskerchen M, Collett MS. Pestivirus gene expression: protein p80 of bovine viral diarrhea virus is a proteinase involved in polyprotein processing. Virology. 1991 Sep;184(1):341–350. [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...