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.
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