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Viral 'Fossils' In Our DNA May Help Us Fight Infection (sciencemag.org)

Posted by BeauHD on from the material-culture dept.

sciencehabit writes: In a new study, researchers led by Edward Chuong, a computational biologist at the University of Utah in Salt Lake City, explored whether endogenous retroviruses (ERVs) help us fend off invaders. The scientists scanned three different human cell lines for ERVs in their DNA that could bind to innate immunity transcription factors, which turn on genes to ramp up the immune system's attack against pathogens. They found thousands of ERVs. The researchers predicted that if they remove this viral DNA from the cell, the transcription factors would not function properly, potentially disrupting genes involved in the innate immune response. Using the gene-editing tool CRISPR, they snipped out several endogenous viruses from the cell's DNA. When researchers infected these ERV-depleted cells with the vaccinia virus, they found a much weaker innate immune response that unedited normal cells, the team reports online today in Science. A key immune protein wasn't produced and thus was not fighting the virus. When researchers later added the genes back into the cells experimentally, immune function was restored. This new research provides evidence that "an ancient viral element is assisting us against an infection," Chuong says.

20 comments

  1. This CRISPR stuff is so awesome! by Anonymous Coward · · Score: 1

    John Church can use CRISPR to lengthen my telomeres anytime!

    1. Re:This CRISPR stuff is so awesome! by Anonymous Coward · · Score: 1

      Maybe that was a bit too subtle.

      John Church is a co-inventor of CRISPR and famously promised (in December 2015) to cure aging within 5 years.

      One method currently in human trials is the lengthening of telomeres, which are strands of junk DNA that serve as a buffer; a bit of them gets clipped off every time a cell divides. This sets a cap on human longevity, but lengthening them could (in theory) remove that cap.

    2. Re:This CRISPR stuff is so awesome! by Michael+Woodhams · · Score: 5, Interesting

      Another contrary view is that lengthening telomeres will not only fail to reduce the increase in cancers with age, but could accelerate it. Cell genomes accumulate mutations over time (and cell divisions). Longer telomeres let the cells hang around longer, but don't prevent or repair the mutations. Sometimes, anti-fortuitously, these mutations lead to a cell becoming cancerous. Killing off cells which have accumulated too much damage or divided too many times is one of the body's defenses against cancer, and longer telomeres can delay or defeat this defense.

      (I'm not advocating either viewpoint - I know enough to be aware that the arguments exist, not enough to judge their correctness.)

      --
      Quattuor res in hoc mundo sanctae sunt: libri, liberi, libertas et liberalitas.
    3. Re:This CRISPR stuff is so awesome! by Anonymous Coward · · Score: 0

      Another contrary view is that lengthening telomeres will not only fail to reduce the increase in cancers with age, but could accelerate it. Cell genomes accumulate mutations over time (and cell divisions). Longer telomeres let the cells hang around longer, but don't prevent or repair the mutations. Sometimes, anti-fortuitously, these mutations lead to a cell becoming cancerous. Killing off cells which have accumulated too much damage or divided too many times is one of the body's defenses against cancer, and longer telomeres can delay or defeat this defense.

      (I'm not advocating either viewpoint - I know enough to be aware that the arguments exist, not enough to judge their correctness.)

      You bring up an important point, the thing is though the large majority of research on the topic of telomere lengthening effects and cancer show the following:

      1- Longer telomeres appear to have an anti-cancer effect and not the opposite as one would think
      2- Most cancers involve mutations in mitochondrial DNA as opposed to nuclear DNA (though both do occur in cancer) The important takeaway to this point is that researchers have transplanted and cloned nuclei from cancerous cells and mitochondria from cancerous cells and they find that the cells where the nuclear DNA ends up do not turn into tumors, rather they develop to a point and then either stop functioning or experience Apoptosis (programmed cell death) and where the mitochondria with mutations end up (even if transferred into cells with non-mutant nuclear DNA) end up becoming cancerous. The takeaway is that 95% of cancer involves a critical step of mitochondrial DNA mutation, not nuclear DNA (Where the Telomeres are) mutations.
      3- DNA repair mechanisms in cells where telomeres have been lengthened have superior (read: more youthful) intra and intercellular signaling , which has a potent anti-cancer effect. Generally if one of those mitochondria have a mutation in a cell with longer telomeres, there are numerous mechanisms that can neutralize the mutated mitochondria or the whole cell if things start to get out of control.

      The three points fly in the face of conventional wisdom in terms of how cancer works, but the human genome project and many databases on the statistics on different types of cancer agree with these three points. Fact is, lengthening telomeres improves cell function and longevity and has an anti-cancer effect.

    4. Re:This CRISPR stuff is so awesome! by Michael+Woodhams · · Score: 1

      Thanks for all that. I was unaware that mtDNA had any role in cancer.

      --
      Quattuor res in hoc mundo sanctae sunt: libri, liberi, libertas et liberalitas.
    5. Re:This CRISPR stuff is so awesome! by Bengie · · Score: 1

      Se we need to selectively lengthen telomeres

  2. endogenous viruses by Anonymous Coward · · Score: 0

    So, they're neither male or female? Or both?

    1. Re:endogenous viruses by Darinbob · · Score: 1

      They have evolved beyond such primitive notions that mankind can conceive.

  3. So, Lamarck was right! by Rei · · Score: 0

    What an individual experiences during their lifetime - such as being infected by and then fighting off a disease - can be passed on to their offspring! Next up, they just need to prove that giraffes that stretch their necks the most when feeding produce the longest-necked offspring, and his acquittal will be complete; take that, Darwin!

    --
    Stale pastry is hollow succor to one who is bereft of ostrich.
    1. Re:So, Lamarck was right! by Anonymous Coward · · Score: 0

      The real question is whether or not human DNA is still evolving. Will the changing environmental stimulus or direct human intervention over long periods of time ultimately result in changing human external and internal characteristics.

    2. Re:So, Lamarck was right! by Anonymous Coward · · Score: 1

      The trivially obvious question is

      FTFY

      whether or not human DNA is still evolving.

      Evolution never stops, so of course it is.

      Will the changing environmental stimulus or direct human intervention over long periods of time ultimately result in changing human external and internal characteristics.

      Yes, both of them will.

    3. Re: So, Lamarck was right! by Anonymous Coward · · Score: 0

      This is an article about retroviruses. Most diseases do not modify the host's DNA itself. And neither does neck-stretching. Or perhaps (I hope) you were being cynical.

    4. Re:So, Lamarck was right! by Jesrad · · Score: 1

      Will the changing environmental stimulus or direct human intervention over long periods of time ultimately result in changing human external and internal characteristics.

      That's the frigging point.

      --
      Maybe we deserve this world ?
  4. More a confirmation than a discovery by Chikungunya · · Score: 2

    I mean, this has been studied for many examples in the past but this experimental design results put a lot more weigh on this theory. I could not find the original article so I don't know what they used as a control, but as long as they deleted also equivalent sequences of the genome (not ERVs) without observing the drop of immunity this approach would clearly demonstrate this mechanism.

  5. Question by smooth+wombat · · Score: 1

    In this study they took a sample and edited the gene. This editing showed that removal of these EVRs produced a reduced immune response.

    How much (or many) of these EVRs would have to removed from within a person for this immune deficiency to show? By that I mean, they are altering a single gene within a cell but doesn't the body have multiple copies of the same gene as backup?

    Also, could a blast of radiation alter a single gene enough to cause this lack of immune response in a person? Would it be possible, under some extreme scenario, for the reverse to happen: a common virus turned into a super virus due to it being hit by a high energy radiation burst which then spreads throughout the world because our immune response can't handle this new virus?

    --
    We will bankrupt ourselves in the vain search for absolute security. -- Dwight D. Eisenhower
    1. Re:Question by Livius · · Score: 1

      our immune response can't handle this new virus?

      Maybe if the radiation gave us the right super-powers the problem would be stopping the immune system from ruining everything.

    2. Re:Question by Anonymous Coward · · Score: 0

      our immune response can't handle this new virus?

      Maybe if the radiation gave us the right super-powers the problem would be stopping the immune system from ruining everything.

      I have type 1 diabetes and an out of control immune system is a nightmare for your health. the culprit so far (the jury is still out) appears to be enterovirus and a number of not statistically significant combinations of genes that increase susceptibility to developing type 1 diabetes. Some are born with these types of auto-immune diseases and some develop them throughout life so as to whether the problem is purely genetic or something in the environment or both remains to be completely determined.

      One interesting thing though, there was a 30 year study done in Sweden (I think) that showed very strong statistical indications that the further north you live in Latitude, the higher your chances of developing type 1 diabetes are. (Best as I can tell it would be linked to vitamin D production early in life having some sort of reaction during development, little known fact also, one of the less reported side effects of long term type 1 diabetes is osteoporosis in men and women, so some sort of derangement in vitamin D is further underscored there.)

      I wonder this, after seeing this article.. if there is so much junk DNA from viruses, what are the chances that some immune-modulating DNA sequence exists that we are glossing over, that is more directly responsible for bringing about auto-immune disease as a part of the adaptive immune system throughout life. Yes I know it is a conclusion looking for evidence rather than how science works (going from observation to hypothesis) I am just frustrated that we have not come up with a cure for type 1 diabetes yet.

  6. The effects of this have already been explored by Anonymous Coward · · Score: 0

    Star Trek - TNG: Genesis - Turns Riker into (more of) a neanderthal, turns Troi into a fish, Barclay into a spider...

  7. sounds like a malware database by Anonymous Coward · · Score: 0

    This entirely smells like match patterns that you could find in some anti-viral software.