Human Endogenous Retroviruses: Studies on Transcriptional Activity and Genetic Variability.
Author
Summary, in English
Endogenous retroviruses (ERVs) are believed to be remains of germ-line infections that have become fixed in the population. They are involved in pathophysiological conditions, in mechanisms leading to infection protection, and directly in the physiology of the organism by participating in the regulation of cellular gene expression. It has been estimated that human ERVs (HERVs) make up about 0.6% of the total human DNA content. This study was undertaken to gain insight into the structure and activity of HERV elements.
Initially, we used a PCR-based screening method to identify new HERV sequences by utilizing primers corresponding to conserved regions of infectious and endogenous retroviral gag, pol and env sequences. In one study we identified a set of novel pol sequences, related to the mouse mammary tumour virus (MMTV), which were assigned to six distinct groups (HML-1 to HML-6). We subsequently characterized full-length elements of two HML groups, named HERV- K(HML6) and HERV-K(HML1). In another study, mouse leukemia virus (MLV)-related env sequences encoding putative immunosuppressive sequences were identified.
We investigated the ability of these sequences to be expressed at the RNA-level. The results revealed a differential transcription pattern in human tissues. In addition, the level of transcripts differed between individuals. These studies show that HERV sequences are regulated in a complex fashion.
We also screened human DNA for functional HML reverse transcriptase (RT)-encoding sequences. We found that clones belonging to the HERV-K family produced fusion proteins after induction in E.coli. Enzyme assays indicated that some proteins displayed RT activity, but further investigations are needed to establish this relationship.
In conclusion, we have identified novel HERV sequences, some of which were shown to be full-length retroviral structures. The present investigation also established that HERVs are expressed at different levels in many tissues and cells, which may be of significance. The data presented here will improve the classification of HERV-K related elements and allow detailed studies of a subset of HERV elements.
Initially, we used a PCR-based screening method to identify new HERV sequences by utilizing primers corresponding to conserved regions of infectious and endogenous retroviral gag, pol and env sequences. In one study we identified a set of novel pol sequences, related to the mouse mammary tumour virus (MMTV), which were assigned to six distinct groups (HML-1 to HML-6). We subsequently characterized full-length elements of two HML groups, named HERV- K(HML6) and HERV-K(HML1). In another study, mouse leukemia virus (MLV)-related env sequences encoding putative immunosuppressive sequences were identified.
We investigated the ability of these sequences to be expressed at the RNA-level. The results revealed a differential transcription pattern in human tissues. In addition, the level of transcripts differed between individuals. These studies show that HERV sequences are regulated in a complex fashion.
We also screened human DNA for functional HML reverse transcriptase (RT)-encoding sequences. We found that clones belonging to the HERV-K family produced fusion proteins after induction in E.coli. Enzyme assays indicated that some proteins displayed RT activity, but further investigations are needed to establish this relationship.
In conclusion, we have identified novel HERV sequences, some of which were shown to be full-length retroviral structures. The present investigation also established that HERVs are expressed at different levels in many tissues and cells, which may be of significance. The data presented here will improve the classification of HERV-K related elements and allow detailed studies of a subset of HERV elements.
Department/s
Publishing year
1996
Language
English
Document type
Dissertation
Publisher
Department of Medical Microbiology, Lund University
Topic
- Microbiology in the medical area
Keywords
- virology
- bacteriology
- HERVs
- Human endogenous retrovirus sequences
- reverse transcriptase
- Microbiology
- differential RNA expression.
- mycology
- Mikrobiologi
- bakteriologi
- virologi
- mykologi
Status
Published
Research group
- Clinical Virology, Malmö
Supervisor
- [unknown] [unknown]
ISBN/ISSN/Other
- ISBN: 91-628-2264-0
- ISRN: LUDMEDW/MEMI--1027--SE
Defence date
3 December 1996
Defence time
10:00
Defence place
Segerfalksalen, Wallenberg Neurocentrum, Sölvegatan 17, Lund.
Opponent
- Christine Leib-Mösch (Dr)