Junk DNA goodbye: ERV's fight viral infections (Introduction)

by David Turell , Sunday, July 11, 2021, 16:00 (1021 days ago) @ David Turell

ERV's are ENDOGENOUS RETROVIRAL PROTEINS throughout our DNA:

https://journals.asm.org/doi/full/10.1128/JVI.02299-20

"Long disregarded as junk DNA or genomic dark matter, endogenous retroviruses (ERVs) have turned out to represent important components of the antiviral immune response. These remnants of once-infectious retroviruses not only regulate cellular immune activation, but may even directly target invading viral pathogens. In this Gem, we summarize mechanisms by which retroviral fossils protect us from viral infections. One focus will be on recent advances in the role of ERVs as regulators of antiviral gene expression.

***

"...we see that ERVs work to initiate immune responses to viruses in a variety of ways:

"(A) ERVs use “viral mimicry” where ERV-encoded long non-coding RNA (lncRNA) molecules bind with viral RNA to activate pattern recognition receptors (PRRs) which activate an immune response.

"(B) LncRNAs produced by ERVs can also induce expression of antiviral cytokines, creating a “positive feedback loop enhancing antiviral immune responses.”

"(C) Proteins encoded by ERV DNA can also enhance immune responses by binding with toll-like receptors.

"(D) ERV envelope proteins (called ENVs) are the outer layer of viruses which protects the genetic material inside. ENVs can bind to receptors which harmful viruses might use to enter host cells, blocking them from entering.

"(E) ENV proteins can enter viruses themselves and interfere with the viral life-cycle, inactivating viruses before they infect new host cells.

"(F) ERV proteins can also stop viruses by interfering with viral capsids that have already entered host cells.

'(G) Some ERVs that are neither transcribed nor translated can promote recombination which increases the number of host genes that can be used to target viruses. This is an evolutionary mechanism, but it could explain how ERVs can be a built-in designed mechanism to increase immune responses within a species.

"(H) There are also very important ERV functions for regulating gene expression, as ERVs can act as promoters, enhancers, or transcription start sites for gene expression. The article explains just how common this is:

"This cooption of regulatory elements is not a rare phenomenon, and it has been estimated that about 20% of all transcription factor binding sites in humans are found in HERVs and other transposable elements. In line with this, a meta-analysis of chromatin immunoprecipitation sequencing (ChIP-Seq) data sets identified about 800,000 transcription factor binding sites within HERVs.

"Intriguingly, almost 90% of all HERVs represent so-called solo LTRs [long terminal repeats, which can serve as binding sites to regulate gene expression]. These HERVs lost the prototypical retroviral genes gag, pol, and env due to homologous recombination of their flanking LTR sequences, leaving single LTR promoters in the genome. Due to their activation upon immune stimulation, ERV LTRs have already been termed “landing strips for inflammatory transcription factors” (90), and evidence for their role in regulating cellular immune responses is growing."

Comment: So it turns out viruses can also be good, not bad. My view is God has a reason for everything, and as yesterday's essay shows, we are innocent bystanders in the war of eat or be eaten.