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