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Application of Polymerase Chain Reaction to Hepatitis C Virus Research and Diagnostics

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Diagnosis of Human Viruses by Polymerase Chain Reaction Technology

Part of the book series: Frontiers of Virology ((FRVIROLOGY,volume 1))

Summary

Rapid advances in virology during the 1980s were due, in part, to the development of powerful molecular biological technologies including lambda GT11 immunoscreening (Young and Davis, 1983) and the polymerase chain reaction (PCR) (Saiki et al. 1985). The hepatitis C virus (HCV), which was cloned using lambda GT11 immunoscreening, is the only virus which was discovered by cloning and characterizing the viral genome prior to biochemical isolation and/or visualization of the virus or viral antigens by microscopy. The application of PCR to HCV enabled researchers to overcome some of the technical limitations associated with the relatively low titers of HCV in blood or liver tissue and the absence of an in vitro tissue culture system for the cultivation of HCV. PCR based diagnostics, the rapid accumulation of HCV sequence information and the availability of cDNA/PCR generated cDNA clones for the expression of putative viral antigens has contributed greatly to our understanding of the structure and biology of HCV.

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References

  • Abe K, Inchauspe G (1991) Transmission of hepatitis C by saliva. Lancet 337:248

    Article  PubMed  CAS  Google Scholar 

  • Alter HJ (1985) In: Infection, immunity and blood transfusion. Liss, New York, pp 47–61

    Google Scholar 

  • Alter MJ (1991) Inapparent transmission of hepatitis C: footprints in the sand. Hepatology 14:389–391

    Article  PubMed  CAS  Google Scholar 

  • Alter HJ, Purcell RH, Smith JW, Melpoler JC, Houghton M, Choo Q-L, Kuo C (1989) 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 321:1494–1539

    Article  PubMed  CAS  Google Scholar 

  • Alter MJ, Hadler SC, Judson FN, Mares A, Alexander J, Hu PY, Miller JK, Moyer LA, Fields HA, Bradley DW, Margolis HS (1990) Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. JAMA 264:2231–2235

    Article  PubMed  CAS  Google Scholar 

  • Bianchi L (1981) The immunology of acute type B hepatitis. Springer Semin Immunopathol 3:421–438

    Article  PubMed  CAS  Google Scholar 

  • Bradley DW, Maynard JE (1986) Etiology and natural history of posttransfusion and enterically-transmitted non-A, non-B hepatitis. Semin Liver Dis 6:56–66

    Article  PubMed  CAS  Google Scholar 

  • Bradley DW, Maynard JE, Krawczynski KZ, Popper H, Cook EH, Gravelle CR, Ebert JW (1981) Non-A, non-B hepatitis in chimpanzees infected with a factor VIII agent: evidence of persistent hepatic disease. In: Szmuness W, Alter HJ, Maynard JE (eds) Proceedings of the third international symposium on viral hepatitis, New York. Franklin Institute, New York

    Google Scholar 

  • Bradley DW, Maynard JE, Popper H, Cook EH, Ebert JW, MacCaustland KA, Schable CA, Fields HA (1983) Posttransfusion non-A, non-B hepatitis: physicochemical properties of two distinct agents. J Infect Dis 148:254–265

    Article  PubMed  CAS  Google Scholar 

  • Bradley DW, McCaustland KA, Cook EH, Schable CA, Ebert JW, Maynard JE (1985) Posttransfusion non-A, non-B hepatitis in chimpanzees. Gastroenterology 88:773–779

    PubMed  CAS  Google Scholar 

  • Bradley D, McCaustland K, Krawczynski K, Spelbring J, Humphrey C, Cook EH (1991) Hepatitis C virus: buoyant density of the factor VIII-derived isolate in sucrose. J Med Virol 34:206–208

    Article  PubMed  CAS  Google Scholar 

  • Brillanti S, Garson JA, Tuke TW, Ring C, Briggs M, Masci C, Miglioli M, Barbara L, Tedder RS (1991) Effect of alpha-interferon therapy on hepatitis-C viraemia in community-acquired chronic non-A hepatitis, non-B hepatitis: a quantitative polymerase chain reaction study. J Med Virol 34:136–141

    Article  PubMed  CAS  Google Scholar 

  • Cha T-A, Beall E, Irvine B, Kolberg J, Kuo G, Urdea MS (1991a) Two hepatitis C viral genotypes occur throughout the world (submitted)

    Google Scholar 

  • Cha T-A, Kolberg J, Irvine B, Stempien M, Beall E, Yano M, Choo Q-L, Houghton M, Kuo G, Han JH, Urdea MS (1991 b) Use of a signature nucleotide sequence of the hepatitis C virus for the detection of viral RNA in human serum and plasma. J Clin Microbiol 29 (in press)

    Google Scholar 

  • Chambers TJ, Hahn CS, Galler R, Rice CM (1990) Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44:649–688

    Article  PubMed  CAS  Google Scholar 

  • Chayama K, Saitoh S, Arase Y, Ikeda K, Matsumoto T, Sakai Y, Kobayashi M, Unakami M, Morinaga T, Kumada H (1991) Effect of interferon administration on serum hepatitis-C virus RNA in patients with chronic hepatitis C. Hepatology 13:1040–1043

    Article  PubMed  CAS  Google Scholar 

  • Chen P-J, Lin M-H, Tu S-J, Chen D-S (1991) Isolation of a complementary DNA fragment of hepatitis C virus in Taiwan revealed significant sequence variations compared with other isolates. Hepatology 14:73–78

    Article  PubMed  Google Scholar 

  • Chien DY, Choo Q-L, Tabrizi A, Kuo C, McFarland J, Shuster JR, Moyer DL, Han JH, Alter HJ, Fong CT, Houghton M, Kuo G, Designed chimeric protein for the serodiagnosis of hepatitis C virus infection: significant improvements in HCV antibody detection as compared with the first generation HCV C100-3 ELISA and the synthetic peptide EIA test (manuscript in preparation)

    Google Scholar 

  • Choo Q-L, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362

    Article  PubMed  CAS  Google Scholar 

  • Choo Q-L, Weiner AJ, Overby LR, Kuo G, Houghton M (1990) Hepatitis C virus: the major causative agent of viral non-A, non-B hepatitis. Br Med Bull 46:423–441

    PubMed  CAS  Google Scholar 

  • Choo Q-L, Richman KH, Han JH, Berger K, Lee C, Dong C, Gallegos C, Coit D, Medina-Selby A, Barr PJ, Weiner AJ, Bradley DW, Kuo G, Houghton M (1991) Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci USA 88:2451–2455

    Article  PubMed  CAS  Google Scholar 

  • Cristiano K, Di Bisceglie AM, Hoofnagle JH, Feinstone SM (1991) Hepatitis C viral RNA in serum of patients with chronic non-A, non-B hepatitis: detection by the polymerase chain reaction using multiple primer sets. Hepatology 14:51–55

    Article  PubMed  CAS  Google Scholar 

  • Cuypers HTM, Winkel IN, van der Poel CL, Reesink HW, Lelie PN, Houghton M, Weiner M (1991) Analysis of genomic variability of hepatitis-C virus. Hepatology (in press)

    Google Scholar 

  • Dienstag JL, Alter HJ (1986) Semin Liver Dis 6:67–81

    Article  PubMed  CAS  Google Scholar 

  • Dusheiko GM, Smith M, Schever PJ (1990) Hepatitis transmitted by human bite. Lancet 336:503–504

    Article  PubMed  CAS  Google Scholar 

  • Erlich HA, Gelfand D, Sninsky JJ (1991) Recent advances in the polymerase chain reaction. Science 252:1643–1651

    Article  PubMed  CAS  Google Scholar 

  • Farci P, Alter HJ, Wong D, Miller RH, Smith JW, Jett B, Purcell RH (1990) A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med 325:98–103

    Article  Google Scholar 

  • Fong T-L, Shindo M, Feinstone SM, Hoofnagle JH, Di Bisceglie AM (1991) Detection of replicative intermediates of hepatitis C viral RNA in liver and serum of patients with chronic hepatitis C. J Clin Invest 88:1058–1060

    Article  PubMed  CAS  Google Scholar 

  • Frohman MA, Dush MK, Martin GR (1988) Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci USA 85:8998–9002

    Article  PubMed  CAS  Google Scholar 

  • Fuchs K, Motz M, Schreier E, Zachoval R, Deinhardt F, Roggendorf M (1991) Characterization of nucleotide sequences from European hepatitis-C virus isolates. Gene 103:163–169

    Article  PubMed  CAS  Google Scholar 

  • Garson JA, Preston FE, Makris M, Tuke P, Ring C, Machin SJ, Tedder RS (1990 a) Detection by PCR of hepatitis C virus in factor VIII concentrates. Lancet 335:1473

    Article  PubMed  CAS  Google Scholar 

  • Garson JA, Ring C, Tuke P, Tedder RS (1990 b) Enhanced detection by PCR of hepatitis C virus RNA. Lancet 335:878–879

    Article  Google Scholar 

  • Garson JA, Tedder RS, Briggs M, Tuke P, Glazebrook JA, Trute A, Parker D, Barbara JAJ, Contreras M, Aloysius S (1990c) Detection of hepatitis C viral sequences in blood donations by “nested” polymerase chain reaction and prediction of infectivity. Lancet 335:1419–1432

    Article  PubMed  CAS  Google Scholar 

  • Han JH, Shyamala V, Richman KH, Brauer MJ, Irvine B, Urdea MS, Tekamp-Olson P, Kuo G, Choo Q-L, Houghton M (1991) Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5c untranslated region and poly(A) tails at the 3c end. Proc Natl Acad Sci USA 88:1711–1715

    Article  PubMed  CAS  Google Scholar 

  • He L-F, Ailing D, Popkin T, Shapiro M, Alter HJ, Purcell RH (1987) Determining the size of non-A, non-B hepatitis virus by filtration. J Infect Dis 156:636–640

    Article  PubMed  CAS  Google Scholar 

  • Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Ohkoshi S, Shimotohno K (1991) Hypervariable regions in the putative glycoprotein of hepatitis C virus. Biochem Biophys Res Commun 175:220–228

    Article  PubMed  CAS  Google Scholar 

  • Holland J, Spindler K, Horodyski F, Grabau E, Niehol S, Vander Pol S (1982) Science 215:1577–1585

    Article  PubMed  CAS  Google Scholar 

  • Hosoda K, Yokosuka O, Omata M, Kato N, Ohto M (1991) Detection of partial sequencing of hepatitis-C virus RNA in the liver. Gastroenterology 101:766–771

    PubMed  CAS  Google Scholar 

  • Houghton M, Choo Q-L, Kuo G (1989) European Patent Application 0318216

    Google Scholar 

  • Houghton M, Weiner A, Han J, Kuo G, Choo Q-L (1991b) Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease. Hepatology 14:381–388

    Article  PubMed  CAS  Google Scholar 

  • Infantolino D, Bonino F, Zanetti AR, Lesniewski RR, Barbazza R, Chiaramonte M (1990) Localization of hepatitis C virus (HCV) antigen by immunohistochemistry on fixed-embedded liver tissue. Ital J Gastroenterol 22:198–199

    PubMed  CAS  Google Scholar 

  • Kanai K, Iwata K, Nakao K, Kako M, Okamoto H (1990) Suppression of hepatitis C virus RNA by interferon-a. Lancet 336:245

    Article  PubMed  CAS  Google Scholar 

  • Kaneko S, Unoura M, Kobayashi K, Kuno K, Murakami S, Hattori N (1990) Detection of serum hepatitis C virus RNA. Lancet 335:976

    Article  PubMed  CAS  Google Scholar 

  • Kato N, Hijikata M, Oootsuyama Y, Nakagawa M, Ohkoshi S, Sugimura T, Shimotohno K (1990 a) Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci USA 87:9524–9528

    Article  PubMed  CAS  Google Scholar 

  • Kato N, Yokosuka O, Omata M, Hosoda K, Ohto M (1990 b) Detection of hepatitis C virus ribonucleic acid in the serum by amplification with polymerase chain reaction. J Clin Invest 86:1764–1767

    Article  PubMed  CAS  Google Scholar 

  • Krawczynski K, Beach M, Bradley D, Kuo G, DiBisceglie A, Houghton M, Reyes G, Kim J, Alter M (1991) Hepatitis C virus antigen in hepatocytes: immunomorphologic detection and identification (submitted)

    Google Scholar 

  • Kremsdorf D, Porchon C, Kim JP, Reyes GR, Bréchot C (1991) Nucleotide sequence analysis of a French hepatitis C virus (HCV) isolate. Gene (in press)

    Google Scholar 

  • Kuo G, Choo Q-L, Alter AJ, Gitnick GI, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, Tegtmeier GE, Bonino F, Colombo M, Lee W-S, Kuo C, Berger K, Shuster JR, Overby LR, Bradley DW, Houghton M (1989) An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244:363–364

    Article  Google Scholar 

  • Li JS, Tong SP, Vitvitski L, Trépo C (1991) Seminar of the evidence for two major subtypes of HCV in France and close relatedness of the predominant one with the prototype virus. In: Genetic heterogeneity of hepatitis viruses: clinical implications. Sestriere, Turin, April 1991

    Google Scholar 

  • Martell M, Esteban JI, Quer J, Genesca J, Weiner A, Esteban R, Guardia J, Gomez J (1992) HCV circulates as a population of different but closely related genomes (“Quasispecies” nature of HCV-genome distribution) J Virol 66:3225–3229

    PubMed  CAS  Google Scholar 

  • Ogata N, Alter HJ, Miller RH, Purcell RH (1991) Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proc Natl Acad Sci USA 88:3392–3396

    Article  PubMed  CAS  Google Scholar 

  • Ohkoshi S, Kato N, Kinoshita T, Hijikata M, Ohtsuyama Y, Okazaki N, Ohkura H, Hirohashi S, Honma A, Ozaki T, Yoshikawa A, Kojima H, Asakura H, Shimotohno K (1990) Detection of hepatitis C virus RNA in sera and liver tissues of non-A, non-B hepatitis patients using the polymerase in chain reaction. Jpn J Cancer Res 81:862–865

    Article  PubMed  CAS  Google Scholar 

  • Okamoto H, Okada S, Sugiyama Y, Yotsumoto S, Tanaka T, Yoshizawa H, Tsuda F, Miyakawa Y, Mayumi M (1990) The 5c-terminal sequence of the hepatitis C virus genome. Jpn J Exp Med 60:167–177

    PubMed  CAS  Google Scholar 

  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N (1985) Enzymatic amplification of b-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354

    Article  PubMed  CAS  Google Scholar 

  • Saracco G, Abate M, Brunetto MR, Baldi M, Calvo PL, Manzini P, Rizzetto M, Verme G, Weiner AJ, Polito A, Chien D, Kuo G, Houghton M, Bonino F (1991) Patients with a complete remission of chronic non-A, non-B hepatitis after interferon therapy remain carriers of hepatitis C virus (submitted)

    Google Scholar 

  • Schlauder GG, Leverenz GJ, Amann CW, Lesniewski RR, Peterson DA (1991) Detection of the hepatitis C virus genome in acute and chronic experimental infection in chimpanzees. J Clin Microbiol 29:2175–2179

    PubMed  CAS  Google Scholar 

  • Shibata M, Kudo T, Kajiyama M, Takahashi T, Matsushima M, Kimura H, Kuzushima K, Morishima T (1990) Hepatitis C viral sequences in sera during the acute phase of infection. Am J Med 89:830–832

    Article  PubMed  CAS  Google Scholar 

  • Shimizu YK, Weiner AJ, Rosenblatt J, Wong DC, Shapiro M, Popkin T, Houghton M, Alter HJ, Purcell RH (1990) Early events in hepatitis C virus infection of chimpanzees. Proc Natl Acad Sci USA 87:6441–6444

    Article  PubMed  CAS  Google Scholar 

  • Shyamala V, Han JH, A simple strategy for the detection and quantitation of HCV RNA in infectious sera by PCR amplification (manuscript in preparation)

    Google Scholar 

  • Simmonds P, Zhang LQ, Watson HG, Rebus S, Ferguson ED, Balfe P, Leadbetter GH, Yap PL, Peutherer JF, Ludlam CA (1990) Hepatitis C quantification and sequencing in blood products, haemophiliacs, and drug users. Lancet 336:1469–1471

    Article  PubMed  CAS  Google Scholar 

  • Southern E (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503

    Article  PubMed  CAS  Google Scholar 

  • Takamatsu K, Koyanagi Y, Okita K, Yamamoto N (1990) Hepatitis C virus RNA in saliva. Lancet 336:1515

    Article  PubMed  CAS  Google Scholar 

  • Takamizawa A, Mori C, Fuke I, Manabe S, Murakami S, Fujita J, Onishi E, Andoh T, Yoshida I, Okayama H (1991) Structure and organization of the hepatitis C virus genome isolated from human carriers. J Virol 65:1105–1113

    PubMed  CAS  Google Scholar 

  • Takehara T, Hayashi N, Mita E, Hagiwara H, Ueda K, Katayama K, Kasahara A, Fusamoto H, Kamada T (1991) Detection of minus strand of hepatitis C virus RNA by reverse transcriptase and polymerase chain reaction. Implication for hepatitis C vims replication in infected tissue

    Google Scholar 

  • Takeuchi K, Kubo Y, Boonmar S, Watanabe Y, Katayama T, Choo Q-L, Kuo G, Houghton M, Saito I, Miyamura T (1990) 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 71:3027–3033

    Article  PubMed  CAS  Google Scholar 

  • Tanaka E, Kiyosawa K, Sodeyama T, Nakano Y, Yoshizawa K, Hayata T, Shimizu S, Nakatsuji Y, Koike Y, Furuta S (1991) Significance of antibody to hepatitis C virus in Japanese patient with viral hepatitis: relationship between anti-HCV antibody and the prognosis of non-A, non-B post-transfusion hepatitis. J Med Virol 33:117–122

    Article  PubMed  CAS  Google Scholar 

  • Thaler MM, Park CK, Landers DV, Wara DW, Houghton M, Veereman-Wauters G, Sweet RL, Han JH (1991) Vertical transmission of hepatitis C virus. Lancet 338:17–18

    Article  PubMed  CAS  Google Scholar 

  • Thomas HC, Pignatelli M, Goodall A, Waters J, Karayiannis P, Brown D (1984) Immunologic mechanisms of cell lysis in hepatitis B virus infection. In: Viral hepatitis and liver disease, pp 167–177

    Google Scholar 

  • Ulrich PP, Romeo JM, Lane PK, Kelly I, Daniel LJ, Vyas GN (1990) Detection, semiquantitation, and genetic variation in hepatitis C virus sequences amplified from the plasma of blood donors with elevated alanine aminotransferase. J Clin Invest 86:1609–1614

    Article  PubMed  CAS  Google Scholar 

  • van der Poel CL, Reesink HW, Lelie PN, Leentvaar-Kuypers A, Choo Q-L, Kuo G, Houghton M (1989) Anti-hepatitis C antibodies and non-A, non-B post-transfusion hepatitis in the Netherlands. Lancet 2:297–298

    PubMed  Google Scholar 

  • van der Poel CL, Reesink HW, Schaasberg W, Leentvaar-Kuypers A, Bakker E, Exel-Oehlers PJ, Lelie PN (1990) Infectivity of blood seropositive for hepatitis C virus antibodies. Lancet 335:558–560

    Article  PubMed  Google Scholar 

  • van der Poel CL, Cuypers HTM, Reesink HW, Weiner AJ, Quan S, Di Nello R, Van Boven JJP, Winkel I, Mulder-Folkerts D, Exel-Oehlers PJ, Schaasberg W, Leentvaar-Kuypers A, Polito A, Houghton M, Lelie PN (1991 a) Confirmation of hepatitis C virus infection by new four-antigen recombinant immunoblot assay. Lancet 337:317–319

    Article  PubMed  Google Scholar 

  • van der Poel CL, Cuypers HTM, Reesink HW, Choo Q-L, Kuo G, Han J, Quan S, Polito A, Verstraten JW, van de Wouw JCAM, Schaasberg W, Houghton M, Lelie PN (1991 b) Risk factors in HCV infected blood donors (submitted)

    Google Scholar 

  • Weiner AJ, Kuo G, Bradley DW, Bonino F, Saracco G, Lee C, Rosenblatt J, Choo Q-L, Houghton M (1990 a) Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet 335:1–3

    Article  PubMed  CAS  Google Scholar 

  • Weiner AJ, Truett MA, Rosenblatt J, Han J, Quan S, Polito AJ, Kuo G, Choo Q-L, Houghton M, Agius C, Page E, Nelles MJ (1990 b) HCV testing in low-risk population. Lancet 336:695

    Article  PubMed  CAS  Google Scholar 

  • Weiner AJ, Brauer MJ, Rosenblatt J, Richman KH, Tung J, Crawford K, Bonino F, Saracco G, Choo Q-L, Houghton M, Han JH (1991 a) 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 180:842–848

    Article  PubMed  CAS  Google Scholar 

  • Weiner AJ, Geysen HM, Christopherson C, Hall JE, Mason TJ, Saracco G, Bonino F, Crawford K, Marion CD, Crawford KA, Barr PJ, Miyamura T, McHutchinson J, Houghton M (1992) Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections. PNAS 89:3468–3472

    Article  PubMed  CAS  Google Scholar 

  • Yoneyama T, Takeuchi K, Watanabe Y, Harada H, Ohbayashi A, Tanaka Y, Yuasa T, Saito I, Miyamura T (1990) Detection of hepatitis C virus cDNA sequence by the polymerase chain reaction in hepatocellular carcinoma tissues. Jpn J Med Sci Biol 43:88–94

    Google Scholar 

  • Young RA, Davis RW (1983) Efficient isolation of genes using antibody probes. PNAS USA 80:1194–1198

    Article  PubMed  CAS  Google Scholar 

  • Yuasa T, Ishikawa G, Manabe S, Sekiguchi S, Takeuchi K, Miyamura T (1991) The particle size of hepatitis-C virus estimated by filtration through microporous regenerated cellulose fibre. J Gen Virol 72:2021–2024

    Article  PubMed  CAS  Google Scholar 

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Weiner, A.J., Shyamala, V., Hall, J.E., Houghton, M., Han, J. (1992). Application of Polymerase Chain Reaction to Hepatitis C Virus Research and Diagnostics. In: Becker, Y., Darai, G. (eds) Diagnosis of Human Viruses by Polymerase Chain Reaction Technology. Frontiers of Virology, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84766-0_8

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