Molecular functions of human endogenous retroviruses in health and disease

• Published in: Cellular and molecular life sciences : CMLS 2015-10, Vol.72 (19), p.3653-3675
• Main Authors: Suntsova, Maria, Garazha, Andrew, Ivanova, Alena, Kaminsky, Dmitry, Zhavoronkov, Alex, Buzdin, Anton
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Autoimmune Diseases - genetics; binding sites; Biochemistry; bioinformatics; Biological Evolution; Biomedical and Life Sciences; Biomedicine; Cell Biology; Endogenous Retroviruses - genetics; Endogenous Retroviruses - metabolism; evolution; Gene Expression Regulation - genetics; genes; Genetics; Genomics; Human immunodeficiency virus; Humans; Infectious diseases; landscapes; Life Sciences; Mental disorders; Molecular biology; Nervous System Diseases - genetics; niches; Physiology; proteins; Psoriasis; Retrovirus; Review; Ribonucleic acid; RNA; schizophrenia; sclerosis; Skin diseases; Speciation; transcription factors; Transcription Factors - metabolism; Viruses
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-015-1947-6

Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8 % of human genome. Recent success of high-throughput experimental technologies facilitated understanding functional impact of HERVs for molecular machinery of human cells. HERVs encode active retroviral proteins, which may exert important physiological functions in the body, but also may be involved in the progression of cancer and numerous human autoimmune, neurological and infectious diseases. The spectrum of related malignancies includes, but not limits to, multiple sclerosis, psoriasis, lupus, schizophrenia, multiple cancer types and HIV. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g., by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this paper, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.