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Identification of human endogenous retroviruses with complex mRNA expression and particle formation
R Löwer1, K Boller, B Hasenmaier
1Paul Ehrlich Institute, Langen, Federal Republic of Germany.
Abstract:
Retroviruses comprise strains with considerable disease potential in animals and humans. In addition to exogenous strains transmitted horizontally, endogenous proviruses are transmitted through the germ line. Some of these endogenous retroviruses can be pathogenic in mice and possibly in other animal species. They may also be considered as mobile genetic elements with the potential to produce mutations. In humans, genomic DNA contains numerous endogenous retroviral sequences detected by their partial relatedness to animal retroviruses. However, all proviruses sequenced so far have been found to be defective. In this communication, we describe the expression of a family of human endogenous retrovirus sequences (HERV-K) in GH cells, a teratocarcinoma cell line producing the human teratocarcinoma-derived retrovirus (HTDV) particles previously described by us. Four viral mRNA species could be identified, including a full-length mRNA. The other three subgenomic mRNAs are generated by single or double splicing events. This expression pattern is reminiscent of the more complex control of virus gene regulation observed, for example, with lenti- or spumavirus strains, although HERV-K shows no sequence homology to human T-lymphotropic virus or human immunodeficiency virus. Sequence analysis of expressed HERV-K genomes revealed non-defective gag genes, a prerequisite for particle formation. Open reading frames were also observed in pol and env. Antisera raised against recombinant gag proteins of HERV-K stained HTDV particles in immunoelectron microscopy, linking them to the HERV-K family.
Insights
Human endogenous retroviruses (HERV-K) are expressed in teratocarcinoma cells, producing viral particles. This study reveals non-defective HERV-K gag genes, linking them to observed retroviral particles.
Area of Science:
- Virology
- Genetics
- Molecular Biology
Background:
- Retroviruses, including exogenous and endogenous forms, pose disease risks and can act as mobile genetic elements.
- Human endogenous retroviral sequences (HERV) are present in genomic DNA, but previously sequenced proviruses were found to be defective.
- Teratocarcinoma cell lines offer a model for studying endogenous retroviral expression.
Purpose of the Study:
- To investigate the expression of human endogenous retrovirus K (HERV-K) sequences.
- To characterize the viral particles produced by GH cells, a teratocarcinoma cell line.
- To determine the integrity and potential function of expressed HERV-K genomes.
Main Methods:
- Analysis of mRNA species derived from HERV-K sequences in GH cells.
- Sequence analysis of expressed HERV-K genomes, focusing on gag, pol, and env genes.
- Immunoelectron microscopy using antisera against HERV-K gag proteins to detect viral particles.
Main Results:
- Four distinct HERV-K mRNA species were identified, including a full-length transcript and three subgenomic mRNAs generated by splicing.
- Sequence analysis revealed non-defective gag genes and open reading frames in pol and env genes of the expressed HERV-K genomes.
- HTDV particles produced by GH cells were immunologically linked to the HERV-K family via gag proteins.
Conclusions:
- The expression of HERV-K in GH cells demonstrates the production of viral particles with potentially functional genetic elements.
- The findings suggest that certain HERV-K elements may retain the capacity for retroviral particle formation.
- This research provides evidence linking HERV-K expression to observable retroviral particles, advancing the understanding of endogenous retroviruses.