Endogenous Viral Components (EVC) are genetic material derived from viruses that have become permanent, integrated features of a host organism’s DNA. These sequences represent ancient infection events that occurred in our ancestors millions of years ago, which were then passed down through successive generations. The vast majority of these components in the human genome originate from retroviruses, making them a type of inherited viral fossil. While once considered inert “junk DNA,” these remnants are now recognized as a significant component of our genetic makeup.
Defining Endogenous Viral Components
EVCs are DNA sequences that closely resemble the genetic structure of infectious viruses, primarily retroviruses, which are known as Endogenous Retroviruses (ERVs). Unlike exogenous, or infectious, viruses that circulate freely between hosts, EVCs are fixed within the host’s chromosomes. These elements are molecular remnants of their ancestors, having accumulated numerous mutations and deletions over deep time.
Estimates suggest that EVCs, primarily human endogenous retroviruses (HERVs), account for approximately five to eight percent of the total human genome. This percentage is significantly larger than the portion of the genome that codes for all human proteins.
The structure of an EVC often mirrors that of a retroviral provirus, containing genes for structural proteins, enzymes like reverse transcriptase, and characteristic sequences called Long Terminal Repeats (LTRs). However, most HERVs are defective, meaning the genes needed to produce new infectious viruses have been inactivated by host mechanisms or random mutations. The LTR sequences, which flank the viral genes, are often the most preserved parts of the EVC and can still be biologically active, even if the viral core genes are not.
Integration into the Human Genome
The defining characteristic of an EVC is its vertical transmission, made possible by germline integration. For a viral sequence to become endogenous, it must integrate its genetic material into the DNA of a germ cell (an egg, sperm, or precursor). Once the viral DNA successfully integrates into a germ cell’s chromosome, it becomes a provirus, and the host’s offspring will inherit this sequence in every cell of their body.
The sequence is then passed down through Mendelian inheritance, just like any other host gene. This process contrasts sharply with an active, or exogenous, infection, which integrates only into somatic (non-reproductive) cells and is not passed to the next generation.
Retroviruses are uniquely prone to this process because integration into the host genome is a mandatory step in their natural life cycle. The viral enzyme reverse transcriptase converts the virus’s RNA genome into a double-stranded DNA copy, which is then spliced into a host chromosome by another viral enzyme called integrase.
Biological Functions and Medical Significance
Although most EVCs are non-functional genetic relics, some sequences have been repurposed by the host genome in a process known as molecular domestication. One of the most prominent examples is the syncytin gene, derived from the envelope protein of an ancient retrovirus.
Syncytin is critically involved in the formation of the placenta in humans and other mammals. This viral protein facilitates the fusion of placental cells, creating a layer called the syncytiotrophoblast, which acts as the barrier between the mother’s and the fetus’s blood circulation. This function, originally used by the virus to promote cell-to-cell spread, became a beneficial trait utilized by the host during reproduction.
Beyond coding for proteins, the LTR sequences of EVCs often function as regulatory elements for host genes. These sequences can act as alternative promoters or enhancers, influencing when and where nearby human genes are expressed. This ability to regulate gene expression plays a role in the development of tissues and the host’s response to environmental stimuli.
The misregulation of EVCs also has implications for human health and disease. In some contexts, the expression of certain HERVs, particularly the HERV-K family, has been linked to various forms of cancer. Viral proteins or RNA from these elements may promote tumor growth or trigger an immune response that contributes to the disease state.
Furthermore, the inappropriate activation of EVCs has been implicated in the development of autoimmune disorders. For instance, the expression of HERV proteins or RNA in cells can trigger an inflammatory reaction, which may contribute to the pathology of conditions like multiple sclerosis and systemic lupus erythematosus.