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RnaseH. MA. CA. NC. PR. RT. IN. SU. TM. pro. gag. pol. env. pro. 1. gag. pol. env. 2. U5. R. U5. U3. R. U3. gag. env. 3. transcription. NC. MA. CA. TM. SU. promoter. R. U5. U3. Type 1 transcript. Enhancer. HRE. promoter. Poly A signal. TGTTAT. AATAAA. - PowerPoint PPT Presentation
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HERV Structure
U5U3U5U3
3’ LTR gag
MA CA NCR R
pro pol
PR INRnaseHRT
env
SU TM
5’ LTR PBS PPT
SD SAtranscription
GTGCTAAG TGTTAT
Enhancer promoter RU3 Poly A signal
AATAAA
U5
LTR LTR
transcription regulatory elements cellular gene promoterU3 - unique to the 3’ end of viral genome
R - direct repats present at both ends of viral genome
U5 - unique to the 5’ end of viral genome (RNA)
gag
NCMA CA
pol
INRT
env
SUTM
pro
PR
gag pol envpro
Type 1 transcript
Type 2 transcript
Type 3 transcript
Type 4 transcript
1 23
promoter
U3 R U3 R U5U5 • gag (group specific antigen)
* MA (Matrix)
- located between nucleocapsid and viral envelope
* CA (capsid)
- major structural component
* NC (nucleocapsid)
- packaging the dimer of RNA
• pro (protease) - cleaves gag-pol and env
• pol (polymerase) * RT (reverse transcriptase)
- synthesizes DNA
* IN (intergrase) - intergrates provirus DNA into genome
• env (envelope)
* SU (surface protein)
- spikes on virion that interact with host
* TM (transmembrane)
- mediates virus-host fusion
EST Data
• Expressed Sequence Tags
– Single pass sequences of cDNA clones from different libraries
– High error rate (>1%) mainly frameshifts and insertions/deletions
– Redundant sampling of 5’ and 3’ ends
– Large number in public databases
cDNA
3’ ESTs5’ ESTs
EST lengths vary due to varying polymerase activity
The human ESTs were classified 37 tissues by cDNA library information of CGAP
HESAS (HERV Expression and Structure Analysis System)
Digital expression profiles of human endogenous retroviral families in
normal and cancerous tissues
Kim Tae HyungMarch 20, 2004
Cancer Immunity, Vol. 4, p. 2 (11 February 2004)
Yves Stauffer1, Gregory Theiler1, Peter Sperisen2, Yuri Lebedev3, and C. Victor Jongeneel1
1Ludwig Institute for Cancer Research, Office of Information Technology, Epalinges, Switzerland2Swiss Institute of Bioinformatics, Epalinges, Switzerland3Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Russia
Mapping of HERV proviral sequences to the human genome
EST-based expression profiles of different HERV families
The four expression ontologies are used to annotate cDNA clone libraries
Clustering HERV proviruses according to their expression patterns
Sbit=[lambdaS-(ln K)]/(ln 2)
d=1-[n11/(n11+n10+n01)]
average-linkage agglomerative hierarchical clustering
Bit score >= 36 P-value <= 0.01
Comparison of the expression levels of different HERV families in normal and cancerous tissues
HERV-K proviruses expressed in tissues in which other members of the family are not usually expressed
HERV expression analysis by massively parallel signature sequencing (MPSS)
37 tissues
Analysis of ESTs matching retroviral open reading frames
HERV-K : 66% (63/95) most ESTs matched either pol or env partial ORFsHERV-W : 67% (66/98) 66/66 (100%)HERV-E : 75% (27/36) HERV-H : 41% (74/157) 43/74 (58%)
>150 aa>450 nt
Hs2_22340Testis6,6631
BG723219357
291 517 5163 5376
Hs6_7456
Placenta
59551 357
203 360 1067 1387 BQ365460
107 360 1067 1181 2305 2783
5347 5880
AU140527
AU158537
AU1586295470 58802906 3332 BF991666
Hs6_7456
Lung1
BF881300, BF881993357
3709 3870 4958 53365955
4710 5109 BF882289, BF882291
5164 6079
BF881990, BF881991
Hs1_331531 357 6150
BM668904, BM669312, BM717273, BM705982, BM670153AA197054
408 860
3724 3862
EyeHs5_232891 357 6719
BQ1892302714 2841 5194 5335
Analysis of ESTs matching retroviral open reading frames
HERV-K : 66% (63/95) most ESTs matched either pol or env partial ORFsHERV-W : 67% (66/98) 66/66 (100%)HERV-E : 75% (27/36) HERV-H : 41% (74/157) 43/74 (58%)
>150 aa>450 nt
HERV ORF predictionHERV ORF prediction