Title: Hepadnaviruses
1Hepadnaviruses
2 Hepadnaviruses Retroviruses
Genome DNA RNA
Primer for (-)strand
synthesis Protein tRNA
Terminal
Repeats (LTRs) No Yes Specific integration
site in virus genome No Yes
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4Retrovirus Resemblence There are several feaures
of the hepatitis B virus that closely resemble
the retrovirus family of viruses, which contains
HIRetrovirus Resemblence 1) Hepatitis B uses a
reverse transcriptase to form DNA from RNA as
retroviruses do. 2) The genetic material of both
contains a direct repeat. 3) The DNA polymerase
and RNAse domains of the reverse trasncriptases
are similar. 4)The order and function of the
genes in retroviruses gag, pol, env is the same
as that in Hepadnavirus genes C, P, and S. 5)
Both have oncogenic associations Hepatitis has
been linked to Hepatocellular Carcinoma and HIV
to B cell lymphomas. 6) HBV is known to integrate
into the host genome in some, but not all,
chronically infected patients and HIV always
integrates itself. 7) Transmission is similar for
both viruses although Hepatitis B is more
infectious.
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7The hepadna family of viruses consists of five
viruses One human virus, hepatitis B, and four
animal viruses woodchuck hepatitis virus, ground
squirrel hepatitis virus, Peking duck hepatitis
virus, and other avian hepatitis viruses.
These five viruses are classified together for
the following reasons 1.They are all
enveloped 2. They all contain polymerases that
can repair the viral DNA genome during
replication 3. They produce lipoproteins
containing envelope proteins 4. They infect
species that are closely related to that of their
natural hosts (narrow host range) 5. As the
family "hepadna" (for hepatotropic DNA viruses)
implies, they can produce chronic infections in
liver cells.
8 Hepatitis B is extremely prevalent with
approximately 300-350 million people worldwide
carrying the virus. Chronic infection persists in
25 of children under 5, and 70-90 of infected
adults. In Africa and Asia, up to 20 of the
population are symptomatic carriers.
Approximately 500,000 people die a year from
Hepatocellular Carcinoma
9HBV DNA consists of a longer, complete (-) strand
with a piece missing at a nicked site, as well as
an incomplete () strand (about 15-50 of the DNA
can be single-stranded) The circular genome is
held in a relaxed shape by base pairing of a 240
nucleotide overlap sequence and short direct
repeats between the strands at the 5'
termini. The 5' end of the (-) strand has a
covalently attached protein whereas 5' end of ()
strand contains an oligoribonucleotide.
10Appendix 1 Fig.3 Hepadnaviruses
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12Appendix 1 Fig.4 Hepadna Life Cycle
13Figures
14The genome contains four overlapping open reading
frames S, C, P, and X coded on the (-) strand.
The S gene encompasses three regions the pre-S1,
pre-S2, and S. Three different proteins are
produced by combining these three genes in
different combinations L, the large protein on
the envelope is made by encoding the pre-S1,
pre-S2, and S genes middle-sized proteins on the
envelope (pre-S2 and S gene) and the major
component of the HBsAg, S protein. The P gene
which comprises 80 of the genome encodes a
polymerase capable of acting as a DNA polymerase,
reverse transcriptase, and RNase H. The C gene
encodes the HBcAg (core antigen). The X gene
encodes a protein that is essential for viral
survival and is thought to be associated with
transcriptional activation. Contains four
overlapping open reading frames S, C, P, and X
coded on the (-) strand.
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18Protein synthesis is tightly regulated at the
transcriptional and translational levels. The two
mRNA transcripts are made, one longer than the
other. The larger one (3.5 kb), longer than the
DNA it is transcribed from due to its 100 bp
terminal repeat, encodes both the capsid proteins
and the products of gene P. This longer
transcript is that which is reverse transcribed
to DNA in the Hepatitis replication scheme. The
smaller mRNA transcript encodes the middle and
major envelope proteins.
19Three transcripts of mRNA, 2.1, 2.4 and 3.4 kb
long, are produced. The l 3.4 kb or "pregenome"
() RNA is the largest and is longer than the DNA
template due to terminal repeat sequences. (The
last RNA produces Hepatits ?.
20Figure 7.22
21Figure 7.23
22Figure 7.24
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26Figure 7.27
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28Figure 7.29
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