Transcription, splicing and genetic structure within the human endogenous retroviral HERV-H family

Sammanfattning: Human endogenous retroviruses (HERVs) are remains of ancient retroviral infections of the germ line and constitute as much as 3 % of the human genome. HERVs are genetic elements that potentially may provide important biological functions by several different mechanisms. The ability to transpose long after the initial insertion into the germ line may provide a potent source of insertional mutagenesis, influencing adjacent cellular genes by the promoter and enhancer functions of the retroviral long terminal repeats (LTRs). Expression of retroviral proteins in human cells may provide important functions both for a resistance to infections by exogenous retroviruses and for normal cell function in the placenta and immune cells. Many of these postulated actions would act through the envelope (Env) glycoproteins, which possess fusogenic and immunosuppressive properties. In the present investigation, various aspects of one of the largest HERV families, HERV-H, was studied. First, HERV-H transcripts potentially encoding immunosuppressive Env proteins were detected in various cell types, e. g. leukocytes and brain tissue. Then the splicing pattern of HERV-H transcripts coding for Env proteins were studied, disclosing complex alternative splicing. Hybrid spliced transcripts containing sequences from HERV-H and another family, HERV-E, were also characterized in these studies. Lastly, the first example of a coding-competent HERV-H element was isolated, possessing a complete open reading frame for the Env protein. The combined results may provide an important basis for studying the presence of immunosuppressive Env protein-encoding HERV-H elements and the expression and function of these proteins.