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Scientists identify new, beneficial function of endogenous retroviruses in immune response

Bob

Senior Member
Messages
16,455
Location
England (south coast)
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
"...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
 

snowathlete

Senior Member
Messages
5,374
Location
UK
Interesting because I have wondered for a while if ERVs might have some sort of purposeful role, though I always thought it might be more viral focused.
 

natasa778

Senior Member
Messages
1,774


Could easily be behind the observed lowered risk of Multiple Sclerosis in HIV+ on HAART

While not clear if this is due to some effect of HIV itself on the immune system, or the effect of HAART therapy (since records are messy: "...We have had to make reasonable assumptions about the likelihood of our exposed HIV cohort being treated with cART during the period of observation") the authors speculate:

Our investigation revealed that having HIV, and presumptively being on HAART, provided a significant and potentially protective effect in relation to the risk of development of MS. The magnitude of this effect (>60%) is at the highest level of any prognostic risk factor investigated to date.

... The unresolved question is that after almost 20 years of available cART, why do there seem to be almost no documented cases of patients, in the literature so far, with coexisting MS and HIV? Given that both MS and HIV result affect the immune system, it is interesting to note that no pharmaceutical companies who produce therapies for either HIV or MS (no companies produce therapies for both HIV and MS) have guidelines on how to treat patients who have HIV and MS. In fact, medical and marketing personnel at companies that produce MS disease modifying treatments (DMTs) do not recall ever receiving an inquiry about how to use these DMTs in patients with HIV who are taking cART (personal communication). ...
 

natasa778

Senior Member
Messages
1,774
This is also super interesting:

This study was performed in order to investigate the prevalence of Sjögren-like syndrome (SLS) in the highly active anti-retroviral therapy (HAART) era in a cohort of HIV-1-positive Greek patients.

... The results of this study are significant because they prove that SLS disappears histologically from the mouth after successful HAART. It is possible that anti-retroviral agents exert a direct or indirect action on the epithelial cells of the exocrine glands.
http://rheumatology.oxfordjournals.org/content/42/10/1164.full

btw they also mention

Moreover, the older anti-rheumatic agent hydroxychloroquine has been shown to decrease HIV replication and has been studied recently as an alternative anti-retroviral medication, together with zidovudine and hydroxyurea, in developing countries [9]. These two observations indicate that the immune mechanisms of HIV infection are of profound therapeutic interest. The present study was designed to assess the possible effect of HAART on SLS.
 

anciendaze

Senior Member
Messages
1,841
While they're at it why don't they mention that HERV-W is active during formation of the placenta? The problem is less that these ERVs exist than that they are active during a variety of disease states. It seems fairly straightforward to see what happens if this activity is suppressed, but strangely this has been very slow to happen.