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HDV infected patients with active HBV replication carry distinct mutations in HBV reverse
transcriptase
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Elham Shirvani-Dastgerdi Supervisor: Prof. Dr. med. Frank Tacke Director: Prof. Dr. med. Christian Trautwein Viral Hepatitis and Immunobiology Lab, Gastroenterology and Metabolic Disorders, University Hospital Aachen, RWTH Aachen University
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Out look
- Introduction to HBV-HDV virion structures and HBV DNA fragments
- Study cases and analysis tools
- Results and discussions
- Conclusion
- Acknowledgment
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HBV & HDV Structures
Photo from Swiss Institute of bioinformatics (http://viralzone.expasy.org/)
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HDV is a replication defective, helper
(HBV) dependent ssRNA virus that
requires the surface antigen of HBV
(HBsAg) for the encapsidation of its
own genome
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HDV serological & clinical features
HBV/HDV
Coinfection HDV
Superinfection
Acute
Hepatitis
Chronic
Hepatitis
Fulminant
Hepatitis
http://www.uptomed.ir
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n Due to the overlapping pattern of HBV genome, changes in one gene
may lead to the overlapped gene alteration
HBV genomic fragment selection for amplification & sequencing
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Study sample
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HBV HBV,HDV Total
Number of HBsAg + patients
64%(71)
36%(40)
111
Female Male
22.5%(16) 77.5%(55)
25%(10) 75%(30)
23.5%(26) 76.5%(85)
Disease phase All Chronic
What are the differences between these variants and those of MI cases???
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D.I
M
.I
Sequence analysis of samples using Stanford database (A) and Consensus WT sequence (B) for double infected (DI) & mono infected (MI) patients
A B Consensus Wt HBV,D1 genotype
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C
B 1.07%
2.65%
0.00%
0.50%
1.00%
1.50%
2.00%
2.50%
3.00%
Stnf.Program Consensus.Seq
Mu
tati
on
%
A
RT sequence analysis results of D.I patients using Stanford database (A) and consensus WT sequence (B). Comparison of A & B results (C)
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
1
16
31
46
61
76
91
10
6
12
1
13
6
15
1
16
6
18
1
19
6
21
1
22
6
24
1
25
6
27
1
28
6
30
1
31
6
33
1
Mu
tati
on
Occ
urr
en
ce
RT mutation position
0
1
2
3
4
5
6
7
1
15
29
43
57
71
85
99
11
3
12
7
14
1
15
5
16
9
18
3
19
7
21
1
22
5
23
9
25
3
26
7
28
1
29
5
30
9
32
3
33
7
Mu
tati
on
Occ
urr
en
ce
RT mutation position
D.I
D
.I
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0
1
2
3
4
5
6
7
1
15
29
43
57
71
85
99
11
3
12
7
14
1
15
5
16
9
18
3
19
7
21
1
22
5
23
9
25
3
26
7
28
1
29
5
30
9
32
3
33
7
Mu
tati
on
Occ
urr
en
ce
RT mutation position
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
1
15
29
43
57
71
85
99
11
3
12
7
14
1
15
5
16
9
18
3
19
7
21
1
22
5
23
9
25
3
26
7
28
1
29
5
30
9
32
3
33
7
Mu
tati
on
Occ
urr
en
ce
RT mutation position
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RT mutation occurrence in HBV D.I (A) and M.I (B) patients. Mutation comparison in RT (C) and a-determinant sequences (D)
A
B
0.77%
2.65%
0.00%
0.50%
1.00%
1.50%
2.00%
2.50%
3.00%
M.I/ RT D.I/ RT
C
1.40%
8%
0.00%
1.00%
2.00%
3.00%
4.00%
5.00%
6.00%
7.00%
8.00%
9.00%
M.I/RT-a-d D.I/RT-a-d
D
D.I
M.I
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0
0.5
1
1.5
2
2.5
3
3.5
4
4.51
12
23
34
45
56
67
78
89
10
0
11
1
12
2
13
3
14
4
15
5
16
6
17
7
18
8
19
9
21
0
22
1
Mu
tati
on
Occ
urr
en
ce
HBsAg mutation position
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
1
13
25
37
49
61
73
85
97
10
9
12
1
13
3
14
5
15
7
16
9
18
1
19
3
20
5
21
7
Mu
tati
on
Occ
urr
en
ce
HBsAg mutation position
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S-HBsAg mutation occurrence in HBV D.I (A) & M.I (B) comparison of A&B (C) & a-determinant mutations in D.I & M.I patients (D)
1.50% 1.60%
0.00%
0.50%
1.00%
1.50%
2.00%
M.I/S-HBsAg D.I/S-HBsAg
1.60%
5.10%
0.00%
1.00%
2.00%
3.00%
4.00%
5.00%
6.00%
M.I/a-d.S-HBsAg D.I/a-d.S-HBsAg
A
B
C
D
D.I
M
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Conclusion
• Although the mechanism of HBV replication suppression in the presence of HDV
is not clear yet, this study suggests that emerging various mutations in RT region
of HBV might be related to HBV rehabilitation
• HBV mutations, specially those in RT, are not only important in terms of
developing drug resistance phenotypes but also because of making virions able
to scape from immune response or to acquire replication capacity even in
suppressive condition
• Considering the importance of host immune response against HBsAg, vaccination
against HBV is still the best option to provide enough protection against the
disease. However, vaccination itself needs reconsiderations according to the
presence of vaccine/immune scape variants
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Acknowledgment
This study was done in Gastroenterology and Metabolic Disorders department in University Hospital of Aachen (RWTH) and in collaboration with Baqiatallah Research Center for Gastrointestinal and Liver Diseases, Tehran, Iran.
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