Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen

Valenzuela, Pablo; Gray, Patrick W.; Quiroga, Margarita; Zaldivar, Josefina; Goodman, Howard M.; Rutter, William J.

doi:10.1038/280815a0

Cited by 291 publications

(137 citation statements)

References 28 publications

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“…Purified, formaldehyde-treated antigen, isolated from human plasma, is an effective vaccine for the prevention of hepatitis B infection (7). Recently, the HBsAg gene has been cloned in yeast (8)(9)(10)(11) and a vaccine has been made that is safe and immunogenic in humans (12,13) and is effective in preventing hepatitis B infection in chimpanzees (14).…”

Section: Introductionmentioning

confidence: 99%

Multiple chemical forms of hepatitis B surface antigen produced in yeast.

Wampler¹,

Lehman²,

Boger³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Hepatitis B surface antigen (HBsAg) has been extracted from yeast cells that produce HBsAg. These cells contain the gene for surface antigen carried on a plasmid that replicates in the cells. Analysis of the yeast-derived HBsAg by sucrose gradient centrifugation and by polyacrylamide gel electrophoresis shows that the antigen that is initially released from yeast cells is a high molecular weight aggregate of the fundamental Mr 25,000 subunit. Unlike HBsAg derived from human plasma, the yeast antigen is held together by noncovalent interactions and can be dissociated in 2% NaDodSO4 without the use of reducing agents. During in vitro purification of the yeast antigen, some disulfide bonds form spontaneously between the antigen subunits, resulting in a particle composed of a mixture of monomers and disulfide-bonded dimers. Treatment with 3 M thiocyanate converts the 20-nm particles into a fully disulfide-bonded form that is not disrupted in NaDodSO4 unless a reducing agent is added. This disulfidebonded particle resembles the naturally occurring, plasmaderived surface antigen particle, and the in vitro formed particle has been used to prepare a vaccine for humans against hepatitis B virus infection.

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Section: Introductionmentioning

confidence: 99%

Multiple chemical forms of hepatitis B surface antigen produced in yeast.

Wampler¹,

Lehman²,

Boger³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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“…The complete nucleotide sequences of the cloned HBV (11,27,38,40) and the related woodchuck hepatitis virus (10) define the major viral protein coding regions. The organization of genetic information is compact: four reading frames (A, B, C, and S) are found in the viral long strand and one small open reading frame (D) is found in the short strand.…”

mentioning

confidence: 99%

Transcription of hepatitis B virus by RNA polymerase II.

Rall¹,

Standring²,

Laub³

et al. 1983

Mol. Cell. Biol.

119

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We employed an in vitro cell-free transcription system to locate RNA polymerase II promoters on the hepatitis B virus genome. The strongest promoter precedes the surface antigen (HBsAg) gene, which is comprised of a long (500 base pairs) presurface region as well as the mature HBsAg coding sequence. The origin of this transcript was localized by using truncated templates and S1 endonuclease.mapping. The activity of the promoter was confirmed in transfection experiments in which the complete HBsAg gene was introduced into monkey kidney cells via a simian virus 40 expression vector. A second RNA polymerase II promoter preceding the HBcAg gene was also active in the cell-free system. The presence of multiple promoters in the hepatitis B virus genome suggests that the relative levels of viral-specific proteins detected in liver and serum may reflect differential or regulated promoter efficiency.Hepatitis B virus (HBV) is a partially singlestranded DNA virus whose host range is restricted to humans and chimpanzees (reviewed in reference 37). The complete nucleotide sequences of the cloned HBV (11,27,38,40) and the related woodchuck hepatitis virus (10) define the major viral protein coding regions. The organization of genetic information is compact: four reading frames (A, B, C, and S) are found in the viral long strand and one small open reading frame (D) is found in the short strand. The viral surface (S) and core (C) protein coding sequences have been identified and incorporated into both procaryotic (9, 27) and eucaryotic (8, 19a, 25, 32, 35) expression vectors, generating products that react with antibodies directed against these antigens (HBsAg and HBcAg). The predicted sequences suggest that the surface antigen is a transmembrane protein, whereas on the basis of the protamine-like COOH terminal region (40), the core antigen is a DNAbinding protein. The S gene has a long 5' leader sequence and the C gene has a shorter 5' leader upstream from the mature coding regions, suggesting that both proteins could be synthesized as precursors. Of the remaining two long-strand open reading frames, the larger (A, -80% of the viral genome) presumably encodes the viral DNA polymerase. This gene overlaps part of the C gene, all of the S gene, and part of the B gene but would be translated with a different register. No specific protein has yet been associated with the smaller reading frame (B).This sequence information has not resulted in a detailed characterization of HBV promoters of RNA transcripts, mainly due to the lack of a reproducible tissue culture system for viral propagation. The definition of HBV promoters is important for (i) determining how the viral genetic information is expressed, (ii) assessing a possible oncogenic role of integrated HBV sequences, and (iii) studying replication, which has recently been proposed to involve reverse transcription of a full-length viral RNA transcript (36). The HBV DNA sequence provides some information on potential transcription signals such as TATA boxes and AATAAA-directed p...

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“…Beginning in 1975, a trickle of adenovirus DNA sequence data has by now increased to a continuingflood (Steenbergh et aL, 1975;Arrand & Roberts, 1979;Akusj~irvi & Pettersson, 1979;Herisse et aL, 1980;van Ormondt et aL, 1980). In 1979 the hepatitis B virus genome sequence was published, as deduced from cloned DNA fragments (Charnay et al, 1979;Pasek et al, 1979;Valenzuela et al, 1979). There are now appearing fairly large amounts of sequence data on retroviruses, as DNAs (Czernilofsky et aL, 1980;Sutcliffe et aL, 1980).…”

Section: The Fifth Fleming Lecture 3 History Of Nucleic Acid Sequencingmentioning

confidence: 99%

Structural Analysis of Animal Virus Genomes: The Fifth Fleming Lecture

McGeoch¹

1981

Journal of General Virology

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Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen

Cited by 291 publications

References 28 publications

Multiple chemical forms of hepatitis B surface antigen produced in yeast.

Multiple chemical forms of hepatitis B surface antigen produced in yeast.

Transcription of hepatitis B virus by RNA polymerase II.

Structural Analysis of Animal Virus Genomes: The Fifth Fleming Lecture

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