1. HERV with transcriptional potential in the brain
Yi Joo-Mi
Molecular Biology and Phylogeny Laboratory

2. HERV and Brain disease Proc Natl Acad Sci U S A. 2001 98:4634-4639
Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Karlsson H, Bachmann S, Schroder J, McArthur J, Torrey EF, Yolken RH
J Neurovirol May;6 Suppl 2:S67-75.
Particle-associated retroviral RNA and tandem RGH/HERV-W copies on human chromosome 7q: possible components of a 'chain-reaction' triggered by infectious agents in multiple sclerosis? Perron H, Perin JP, Rieger F, Alliel PM.
Int MS J Apr;10(1):22-8.
Endogenous retroviruses and MS: using ERVs as disease markers. Clausen J.

3. Journal of Human Genetics. 2003 48: 575-581
Human endogenous retroviruses with transcriptional potential in the brain
Nakamura A, Okazaki Y, Sugimoto J, Oda T, Jinno Y
◈ Two HERV loci that are expected to retain the transcriptional activity in the brain
(1q21-q22, 22q12)
◈ These region are overlapped with schizophrenia susceptible loci,
SCZD9 and SCZD4
◈ HERV-H (HSN28H9) on 22q12 was located in the opposite direction 4kb
downstream of Synapsin III gene
◈ possibility of activation in teratocarcinoma cell lines from male and female origin

4. Materials and Method
1. RNA isolation from Tera 1 and NTera 2 (teratocarcinoma cell line)
2. EST database screening
HERV-H, E, F, W, and HML6 from the GenBank database.
EST database screening – collected ESTs from each family
3. RT-PCR in Tera 1, NTera 2, and fetal brain
HERV-K
HERV-H LTR, gag
HERV-F LTR
HML6
4. Identification of potentially active HERV loci

5. Total 600 HERV ESTs were collected from the screening for 5 HERV families
111 were derived from neuronal tissues or cell lines

6. Genomic structures HERV-K Type I HERV-K RT-PCR exon Splicing pattern
Structure of the typical HERV-K genome, cDNA from GenBank database,
and RT-PCR products.
[ ] : 292bp deletion

7. Activated HERV-K loci in teratocarcinoma cell lines
-- common to all teratocarcinoma
-- dependent on their male and female origin
HERV-K108 – potentially active locus in the testis

8. RT-PCR analyses

9. 45%
20%
70%
Identification of transcriptionally active loci: HERV-K102, HERV-F, HML6-1
The frequency of HERV-H (HSN28H9) is very low (3/20)
LTR-F1; solitary LTR in which the transcription of gene ends
HML6-1; start upstream of the 5’LTR

10. Discussion
◈ Finally, HERV-K102 on 1q21-q22 and HERV-H on 22q12 have potentially
transcriptionally active HERVs in the brain
- These HERV loci could be candidates for further analyses discussed
normal and neuropsychiatric disease
◈ These HERV loci are expected to retain the enhancer/promoter activity in
the brain
◈ These region are overlapped with schizophrenia susceptible loci,
SCZD9 (1q21-22) and SCZD4 (22q11-q13)
◈ HERV-K102 might affect the expression of genes as an enhancer
 ADAR(adenosin deaminase gene); RNA editing of glutamate receptors and
serotonin receptor 5-HT2c by targeting double-strand region of their mRNA
◈ HERV-H (HSN28H9) on 22q12 was located in the opposite direction 4kb
downstream of Synapsin III gene; synaltogenesis, regulation of neurotrnasmitter
release

11. Numerous characterized and uncharacterized genes are present near HERVK102
The genes encoding for
rho/rac guanine nucleotide exchange factor 2 (ARHGEF2), RAS oncogene-related
protein (RAB25)
ephrin-A1 (EFNA1), ephrin-A3(EFNA3), ephrin-A4 (EFNA4)
The uncharacterized G-protein coupled receptor-like gene (LOC128227) may
be relevant to neuronal functions, neurodevelopment, and neuropsychiatric
disorders.