Bob
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This is some new research that demonstrates that endogenous retroviruses (in mice) play an integral, active and positive role in the immune system (in mice at least) specifically to stimulate B cells to make antibodies in some circumstances.
This is purely my own speculation, but my thinking is that perhaps if these particular ERVs are over-active, or over-expressed, for whatever reason, then they might over-stimulate B cells to produce too many antibodies. And in such a circumstance, perhaps anti-retrovirals might suppress their expression.
So this might be of interest in anyone who is interested in HERVs, and the potential of anti-retro-virals to suppress HERVs and to treat ME/CFS. And it might be of general interest for anyone interested in the immune system.
As far as my understanding goes the ERVs are active against polysaccharides, and so stimulate antigens to polysaccharides rather than to proteins.
News Article:
Scientists identify new, beneficial function of endogenous retroviruses in immune response
December 18, 2014
http://www.sciencedaily.com/releases/2014/12/141218141057.htm
Another News Article:
Repurposed Retroviruses - B cells have commandeered ancient viral sequences in the genome to transmit antigen signals.
By Ruth Williams | December 18, 2014
http://www.the-scientist.com/?articles.view/articleNo/41707/title/Repurposed-Retroviruses/
Research Paper:
MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses
Ming Zeng et al.
19 December 2014
Science
Vol. 346 no. 6216 pp. 1486-1492
DOI: 10.1126/science.346.6216.1486
http://www.sciencemag.org/content/346/6216/1486.abstract
This is purely my own speculation, but my thinking is that perhaps if these particular ERVs are over-active, or over-expressed, for whatever reason, then they might over-stimulate B cells to produce too many antibodies. And in such a circumstance, perhaps anti-retrovirals might suppress their expression.
So this might be of interest in anyone who is interested in HERVs, and the potential of anti-retro-virals to suppress HERVs and to treat ME/CFS. And it might be of general interest for anyone interested in the immune system.
As far as my understanding goes the ERVs are active against polysaccharides, and so stimulate antigens to polysaccharides rather than to proteins.
News Article:
Scientists identify new, beneficial function of endogenous retroviruses in immune response
December 18, 2014
http://www.sciencedaily.com/releases/2014/12/141218141057.htm
"...researchers at UT Southwestern Medical Center and Karolinska Institutet in Stockholm, Sweden, found that endogenous retroviruses (ERV) also play a critical role in the body's immune defense against common bacterial and viral pathogens."
""We have found that ERV fulfill at least one beneficial function critical to producing protective antibodies.""
"Writing in the journal Science, the researchers found that when B cells are activated by large polymeric antigens such as polysaccharides of bacteria, they rapidly produce protective antibodies in what is termed the Type II T-independent antibody response. This response, central to the body's defense against common bacterial and viral pathogens, is dependent on ERV."
"Within activated B cells, the ERV are driven to express RNA copies of themselves, which in turn are copied into DNA by an enzyme called reverse transcriptase. The RNA copies of ERV are detected by a protein called RIG-I, and the DNA copies are detected by another protein called cGAS. These two proteins send further signals that enable the B cells to sustain their activated state, proliferate, and produce antibodies."
""These findings suggest that both the RNA and DNA sensing pathways play an important role in detecting ERV and activating adaptive immune responses," said Dr. Chen, who is also an investigator of Howard Hughes Medical Institute and holds the George L. MacGregor Distinguished Chair in Biomedical Science.
Mice lacking elements of the RIG-I or cGAS pathways show diminished responses to type II T-independent antigens, and mice lacking both pathways show almost no antibody response at all. Moreover, reverse transcriptase inhibiting drugs also partially inhibit the type II T-independent antibody response."
Another News Article:
Repurposed Retroviruses - B cells have commandeered ancient viral sequences in the genome to transmit antigen signals.
By Ruth Williams | December 18, 2014
http://www.the-scientist.com/?articles.view/articleNo/41707/title/Repurposed-Retroviruses/
"TI-2 antigens are so named because they can stimulate B cells to produce antibodies in a T cell-independent (TI) manner. Unlike protein antigens—which need T helper cells to interact with and stimulate the B cell in which they are being processed—TI antigens can stimulate B cells on their own. TI-2 antigens tend to be large polysaccharides with repetitive structures, such as those that encapsulate certain bacteria and viruses. It is known that they interact via multiple crosslinks with B cell receptors, but the subsequent pathway to antibody production was a mystery."
"It turned out that TI-2 stimulated B cells to produce a wide range of endogenous retrovirus (ERV) RNA transcripts from across the genome. These transcripts were then also reverse-transcribed into DNA. Indeed, the team showed that treating the mice with drugs that inhibit reverse transciptase not only reduced ERV-derived DNA, but also the production of TI-2-induced antibodies."
"Although the findings indicate a role for ERV RNAs and DNAs in TI-2 signaling, a definitive experiment—blocking activation of all ERV transcription across the genome to see whether antibody production is affected—would be very difficult to perform, said Trono. “You’re not going to be able to inactivate 500,000 different sequences.”"
"“It appears that [their expression] was taken advantage of, at least in the B cells . . . and has become an integrated part of the B cell receptor signaling mechanism.”"
Research Paper:
MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses
Ming Zeng et al.
19 December 2014
Science
Vol. 346 no. 6216 pp. 1486-1492
DOI: 10.1126/science.346.6216.1486
http://www.sciencemag.org/content/346/6216/1486.abstract