Human endogenous retroviruses: our genomic fossils and companions

Abstract

Approximately 8% of the human genome, over four-times more than its protein-coding regions, comprises sequences of viral origin that are known as human endogenous retroviral elements (HERVs). Present in the genome of all human cells, HERVs resulted from the integration of now-extinct exogenous retroviruses into mammalian ancestor germ cells or their precursors on several occasions, sometimes as long as tens of millions of years ago. Most HERVs have become silenced because of mutations such as substitutions, insertions, or deletions, and as a result of epigenetic changes, and are vertically transmitted in the population. Considered for a long time to be part of the "junk DNA", HERVs were shown, in more recent years, to perform critical functions in the host. Two of the very few HERVs known to encode functional proteins, syncytin-1 and syncytin-2, are critical during embryogenesis, when they contribute to the formation of the placenta and facilitate tolerance of the maternal immune system towards the developing fetus. Homologs of syncytin-encoding genes were described in several other species, and it appears that during evolution they were stably endogenized into the respective genomes on multiple occasions and became co-opted for critical physiological functions. The aberrant expression of HERVs has been linked to conditions that include infectious, autoimmune, malignant, and neurological diseases. HERVs, our genomic fossils and storytellers, provide a fascinating and somewhat mysterious insight into our co-evolution with viruses, and will undoubtedly offer many teachings, surprises, and paradigm changes for years to come.

Nanopore-based metagenomics analysis reveals microbial presence in amniotic fluid: A prospective study

“…HERVs, which constitute approximately 8% of the human genome, are present in the genomes of all human cells and have emerged through multiple integrations of exogenous retroviruses into germ cells or their precursors in mammalian ancestors. Historically considered "junk DNA," recent research suggests HERVs might play significant roles in embryonic development and immune system regulation [ 76 ]. Earlier investigations also detected Pseudomonas in AF and linked it to patent ductus arteriosus (PDA) in premature infants [ 77 ] and septicaemia-induced miscarriages [ 78 ].…”

Precise Therapy Using the Selective Endogenous Encapsidation for Cellular Delivery Vector System

“…Vertebrate genomes have integrated sequences of human endogenous retroviruses (HERVs), which were acquired during the evolution of vertebrate organisms [ 72 ]. In humans, retroviruses make up more than 8% of the human genome [ 73 , 74 ], and nowadays they are more likely symbionts than parasites [ 75 ]. As an example, two HERVs encode the functional proteins syncytin-1 and 2 which are very important during the embryogenesis of fetuses.…”

“…As an example, two HERVs encode the functional proteins syncytin-1 and 2 which are very important during the embryogenesis of fetuses. These proteins participate in placenta formation and the adaptation of the maternal immune system to the fetus [ 73 ].…”

“…Now, it is well known that ERVs and LTR (long terminal repeat) retrotransposons make up a substantial part of the human genome. These sequences were integrated into the human genome millions of years ago [ 73 , 74 ].…”

“…Endogenous retroviruses (retrogenic viruses) have lost their original functions, but they may play important roles in human physiology, as their genes may produce specific proteins [ 73 ]. Retroelements retain their functions and play a role in the binding and transfer of mRNA and the formation of capsids in the cell [ 110 ].…”