Sunday 18 November 2012

Human Endogenous Retroviruses (HERVs) and autism

Please don't be put off by the title of this post or the jargon it contains. I merely offer some discussion on a paper recently published at Emanuela Balestrieri and colleagues* (open-access) on the expression of Human Endogenous Retroviruses (HERVs) in cases of autism.

The Martians are a comin' @ Wikipedia  
HERVs are probably best described as the genetic remnants of viruses stored in the human genome. Consider this: over the course of the evolution of humankind, we have been in contact with quite a few pathogens. This includes bacteria, parasites and viruses. Over the generations, our exposure to these pathogens leaves a mark, little genetic pieces of things like viruses are left in our genome and are passed on down the generations (germline), seemingly with no useful function (seemingly!). In effect we are all part virus.

I think about the words of Morgan (More Than) Freeman at the end of the film War of the Worlds - the Tom Cruise version - and his description of humans earning their right to exist as a consequence of our evolutionary battle with such pathogens. We adapt, we earn protection (immunity) from such pathogens as the generations pass by, and along the way we also carry and transmit a little piece of them with us. And all that recent chatter about junk DNA probably not just being junk? Well, in among that junk are likely to be HERVs (about 8% of the genome apparently).

So then a few choice details from the Balestrieri paper despite it being open-access:

  • Blood samples drawn from 28 children (aged 3-9 years) were analysed and compared against 28 gender- and age-matched asymptomatic controls.
  • Examining peripheral blood mononuclear cells (PBMCs) immediately and after 72 hours of stimulation in culture, the appearance of retroviral mRNAs derived from 4 HERV families (E, H, K, W) were analysed by qualitative RT-PCR. Real time quantitative PCR was also used to look at the expression of the env sequence for HERV-H and HERV-W (there's a clue there as to what they actually found).
  • Results: samples from their cohort diagnosed with autism - ASD - showed an increased frequency of HERV-H and HERV-W positive samples under both fresh and stimulated conditions. That being said, the significance of the results were not entirely impressive.
  • Expression levels of the env sequence of the 2 HERVs (H & W) suggested some interesting results. HERV-H was more prominently over-expressed in ASD samples for both time periods but significantly so for the fresh samples. HERV-W expression by contrast was significantly lower in the ASD groups compared with controls across both time periods.

The meaning? Well aside from suggesting that HERV-H might, just might, serve as a candidate biomarker for autism (accepting small details like the small current sample size, comorbidity influence and the autisms not necessarily lending themselves to generic biomarkers), I have to say that I'm equally interested in what HERV over- and under-expression might mean to genetics and biology.

I note for example that the authors suggest that "HERVs might actually be considered as emerging pathogens and can be seen as spanning the bridge between genetic predisposition and environmental factors" on the basis that HERVs are part and parcel of human mobile retrotransposon families, the so-called jumping genes. The story goes that HERVs have the capability to alter the structure and functioning of other genes depending on where they land in the genome. Most of the time however HERVs are kept in check by epigenetic means, as per the relationship between methylation and genomic stability. In cases where hypomethylation might be present the mantra: hypomethylation = more genomic instability or less is more (see the paper from Li and colleagues** open-access) seems to apply and HERVs might get more of chance to start expressing. This blog post discussing ERVs in relation to some other research on alcoholism neatly sums up the story bearing in mind its all been boiled down to its very basic elements.

I can't profess to know all the details about HERVs and their potential effects but have easily found related research on, for example, a possible relationship between HERV-W and schizophrenia as per this paper by LeBoyer and colleagues*** bearing in mind the possible implications of certain medication**** (open-access). Indeed the Diem study**** linked to above suggesting that certain medication/s might impact on HERV expression builds upon (a) the growing interest in how certain pharmacotherapies might possess epigenetic-modifying characteristics (see the press release), and (b) again, the regulation of HERV expression by epigenetic means. I'm also minded to included some information about the relationship between HERVs and autoimmune conditions***** if one takes on board some connection between autoimmunity and cases of autism (see this previous post).

It all makes for a really quite interesting hypothesis: that we should ideally have a balanced epigenetic homoeostatic mechanism in place which suppresses those ancient remnants of viruses present in our genome, but when things go awry with epigenetics, we might start to see those viral genes expressing mRNA with potential onward effects. Another far cry from the genes are set model of not so long ago and indeed illustrative of how autism is a very, very, very complicated condition, variably influenced by both genes and environment.

Watch this space on this one.


* Balestrieri E. et al. HERVs expression in autism spectrum disorders. PLoS ONE. 2012; 7: e48831.

** Li J. et al. Genomic hypomethylation in the human germline associates with selective structural mutability in the human genome. PLoS Genetics. 2012: 8: e1002692.

*** LeBoyer M. et al. Human endogenous retrovirus type W (HERV-W) in schizophrenia: A new avenue of research at the gene-environment interface. World J Biol Psychiatry. September 2011.

**** Diem O. et al. Influence of antipsychotic drugs on human endogenous retrovirus (HERV) transcription in brain cells. PLoS One. 2012; 7: e30054.

***** Brodziak A. et al. The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases. Med Sci Monit. 2012; 18: RA80-R88.

---------- Balestrieri E, Arpino C, Matteucci C, Sorrentino R, Pica F, Alessandrelli R, Coniglio A, Curatolo P, Rezza G, Macciardi F, Garaci E, Gaudi S, & Sinibaldi-Vallebona P (2012). HERVs Expression in Autism Spectrum Disorders. PloS one, 7 (11) PMID: 23155411


  1. I found your post fascinating (if a little complicated.) After I watched a BBC science programme on epigenetics and obesity earlier this year I was excited to think of the ramifications this may have for ASD. I am a homeopath with a special interest in autism and ADHD in terms of research and patient treatments. Patients come with stories of ill health and when I include the stories of their parents links can often be made. Toxicity, viruses and other stressors can affect these susceptible children and the results are ASD's. I recently undertook the CEASE Protocol training and see great links in both. Homeopathy seeks to 'balance' patients and maintain homeostasis. Suppressing remnants of viruses and stressors can effectively be 'detoxed' at an energetic level. This might make a credible treatment package to modify the diet, detox energetically and add orthomolecular support? Can you suggest any further reading or research please? Thank you! Joanne Brown BA BSc LCHE RSHom @

  2. Thanks for dropping by Joanne.

    Further reading on HERVs...

  3. How significant is this in the context of 'de novo' gene mutations in autism we keep hearing about ... copy number variations ... deletions, duplications, chromosomal rearrangements...

    How about this for some fresh perspective?

    "A recurrent translocation is mediated by homologous recombination between HERV-H elements"

    ... Homologous recombination between HERVs on the same chromosome is known to cause chromosome deletions, but this is the first report of interchromosomal HERV-HERV recombination leading to a translocation.

    ... Chromosome rearrangements play a major role in intellectual disability, birth defects, and autism [1-3], and many heterogeneous mechanisms have been implicated in the formation of chromosome rearrangements...

  4. Many thanks Natasa.

    As discussed on FB, a potentially very important observation indeed....

  5. Another informative read here (not open access)

    … Endogenous retrovirus-like elements, or ERVs, are an abundant component of all eukaryotic genomes. Their transcriptional and retrotranspositional activities have great potential for deleterious
    effects on gene expression.

    Consequences of such activity may include germline mutagenesis ...


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