The human genome contains the remnants of ancient viral infections known as Human Endogenous Retroviruses (HERVs). These are not active viruses but viral sequences that became a permanent part of our DNA millions of years ago. Collectively, these viral relics and related elements make up approximately 8% of the human genome.
For a long time, these sequences were considered “junk DNA,” evolutionary leftovers with no apparent purpose. However, researchers now recognize these ancient viral codes are not silent passengers. They are an influential component of our genetic makeup, shaping human biology from the earliest moments of development.
The Origin of Viral DNA in Our Genome
The origin of HERVs is tied to the life cycle of retroviruses, like the modern Human Immunodeficiency Virus (HIV). When a retrovirus infects a cell, it uses an enzyme called reverse transcriptase to convert its RNA-based genetic material into a DNA copy. This viral DNA is then transported to the host cell’s nucleus, where an enzyme called integrase inserts it into the host’s chromosomes.
This integrated viral DNA, known as a provirus, becomes part of the host’s genome. The cell’s machinery then reads this new code, producing the components to assemble new viruses. For a provirus to become a permanent, heritable feature, the retrovirus must infect a germline cell, such as a sperm or an egg.
Only an infection of a germline cell ensures that the integrated provirus is passed down from parent to offspring through generations. Over millions of years of evolution, these inherited viral sequences have accumulated mutations, with most losing their ability to produce infectious particles.
From Junk DNA to Functional Elements
Once dismissed as genomic clutter, many HERVs are now understood to be functional elements co-opted for beneficial purposes in human biology. A primary example is the role of HERV-W in placental development. The `env` gene of this ancient virus, originally used to infect cells, has been repurposed by the human body.
This gene produces a protein called syncytin-1, which is fundamental to forming the syncytiotrophoblast, a key layer of the placenta. Syncytin-1 uses its original cell-fusing properties to merge fetal cells, creating the syncytiotrophoblast. This continuous layer of cells forms the primary interface between the mother and fetus.
This layer is responsible for nutrient exchange and helps shield the fetus from the mother’s immune system. Another HERV-derived protein, suppressyn, helps regulate this fusion process.
Beyond placental development, HERVs also contribute to regulating the immune system. Some HERV sequences function as regulatory elements, like promoters or enhancers, that can influence the expression of nearby immune-related genes. The presence of HERV-derived RNA and proteins can also be recognized by the innate immune system, which may prime the body’s defenses against external pathogens.
The Link Between HERVs and Modern Diseases
While many HERVs are either silent or beneficial, the reactivation of these dormant viral sequences has been linked to a range of modern diseases. Environmental triggers like inflammation or other infections can awaken these dormant sequences. This leads to the production of viral proteins that can contribute to disease.
Autoimmune Diseases
The reactivation of HERVs is linked to autoimmune conditions like Multiple Sclerosis (MS) and Systemic Lupus Erythematosus (SLE). The leading hypothesis is “molecular mimicry,” where HERV proteins are so similar to the body’s own proteins that the immune system becomes confused. An attack against the viral proteins may lead the immune system to damage healthy tissues, such as the myelin sheath in MS. The HERV-W family is strongly associated with this condition.
Cancer
The expression of HERVs is also implicated in several types of cancer. The HERV-K family is frequently reactivated in melanoma, breast cancer, and ovarian cancer. HERV-K proteins may contribute to cancer development by promoting cell proliferation, causing cell fusion, or helping tumors evade the immune system. The level of HERV expression can correlate with a poorer prognosis, suggesting these viral elements play an active role in disease progression.
Neurological and Psychiatric Disorders
Neurological and psychiatric disorders have also been linked to these ancient viral remnants. In Amyotrophic Lateral Sclerosis (ALS), the HERV-K family is expressed in the neurons of affected individuals. Studies in mice show that expressing a HERV-K `env` protein in neurons can lead to motor neuron damage. Associations have also been made with schizophrenia, where HERV-W proteins have been detected in some patients, though this connection is an area of ongoing research.
Future of HERV Research
The understanding of HERVs’ dual role in health and disease has opened new frontiers in medical science. Researchers are exploring how to use this knowledge for diagnostics and therapeutics. The specific expression patterns of HERVs in disease states make them promising biomarkers. For example, detecting elevated levels of HERV-K RNA or proteins could aid in the diagnosis or prognosis of cancers like breast cancer, prostate cancer, or melanoma.
This research also extends to developing new therapies. Since some HERV proteins are expressed on the surface of cancer cells but not healthy cells, they are an attractive target for specific treatments. Scientists are designing therapies like monoclonal antibodies that bind to these HERV proteins, flagging cancer cells for destruction by the immune system.
Another approach involves antibody-drug conjugates (ADCs), which are monoclonal antibodies armed with a chemotherapy payload. These ADCs deliver the toxin directly to HERV-expressing tumor cells, minimizing damage to healthy tissue.
Clinical trials are testing these HERV-targeted therapies. For instance, a monoclonal antibody targeting the HERV-W envelope protein has been tested in patients with multiple sclerosis, while therapies targeting HERV-K proteins are being investigated for melanoma and other cancers. This research views these ancient viral components not as evolutionary relics, but as active biological participants that can be targeted to fight modern diseases.