A tissue level atlas of the healthy human virome, 2020

[rvallee]

Background

Human-resident microbes can influence both health and disease. Investigating the microbiome using next-generation sequencing technology has revealed examples of mutualism and conflict between microbes and humans. Comparing to bacteria, the viral component of the microbiome (i.e., the “virome”) is understudied. Somatic tissues of healthy individuals are usually inaccessible for the virome sampling; therefore, there is limited understanding of the presence and distribution of viruses in tissues in healthy individuals and how virus infection associates with human gene expression and perturbs immunological homeostasis.

Results

To characterize the human virome in a tissue-specific manner, here we performed meta-transcriptomic analysis using the RNA-sequencing dataset from the Genotype-Tissue Expression (GTEx) Project. We analyzed the 8991 RNA-sequencing data obtained from 51 somatic tissues from 547 individuals and successfully detected 39 viral species in at least one tissue. We then investigated associations between virus infection and human gene expression and human disease onset. We detected some expected relationships; for instance, hepatitis C virus infection in the liver was strongly associated with interferon-stimulated gene upregulation and pathological findings of chronic hepatitis. The presence of herpes simplex virus type 1 in one subject’s brain strongly associated with immune gene expression. While torque teno virus was detected in a broad range of human tissues, it was not associated with interferon responses. Being notable in light of its association with lymphoproliferative disorders, Epstein-Barr virus infection in the spleen and blood was associated with an increase in plasma cells in healthy subjects. Human herpesvirus 7 was often detected in the stomach; intriguingly, it associated with the proportion of human leukocytes in the stomach as well as digestive gene expression. Moreover, virus infections in the local tissues associated with systemic immune responses in circulating blood.

Conclusions

To our knowledge, this study is the first comprehensive investigation of the human virome in a variety of tissues in healthy individuals through meta-transcriptomic analysis. Further investigation of the associations described here, and application of this analytical pipeline to additional datasets, will be useful to reveal the impact of viral infections on human health.

Landscape of the healthy human virome. The viruses detected in the GTEx dataset are summarized. The results of various subtypes of TTVs, HPVs, and Hubei picornaviruses detected were unified. The viruses for further investigations in Figs. 3, 4, 5, 6, and 7 (EBV, HSV-1, HHV-7, HCV, and TTV) are indicated in bold and colored. The alternative name of each virus is indicated in parentheses. (Left) The level of the transcript of each virus in each human tissue. The averages in the positive samples are shown as a heatmap. (Middle) The positive rate for each virus in each human tissue. (Right) The frequency of the individuals positive for respective viruses is summarized in bar graphs. The numbers of tissues positive for the respective viruses (1, 2–5, or more than 6) are also shown. AAV, adeno-associated virus; HCoV, human coronavirus; RSV, respiratory syncytial virus

 

[rvallee]

Turns out pathogens, whose survival depends on being able to evade and hide from the immune system, are actually good at it. Who knew?!

 

[Jonathan Edwards]

Who knew?!

We have known for decades. Nothing new here I am afraid. Hidden viruses were the explanation for everything when I was a kid sixty years ago.

 

[Tilly]

We have known for decades. Nothing new here I am afraid. Hidden viruses were the explanation for everything when I was a kid sixty years ago.

We what the hell happened for the medical profession to loose that understanding? Why haven't we got the ability to track and trace what happens and why with our autoimmune system and how did all that get blamed on anxiety.

I think there was a Canadian who was looking into tracking every virus you ever had which sounded to me like a jolly good idea but thought that would have been done decades before?

 

[Forbin]

So there's a chance my brain could be harboring tomato spotted wilt virus?

Just as I've long suspected.

 

[Jonathan Edwards]

We what the hell happened for the medical profession to loose that understanding?

It wasn't an understanding. Lots of viruses were found and most of them shown to be irrelevant. The mistake was to think that every unsolved problem was due to a virus - and that mistake keeps popping up every time someone has a new test they want to sell.

We have the ability to track and trace, just incompetent administrators who allow pandemics that we know about to spread. None of this has anything much to do with autoimmunity as far as I am aware. The progress of the 1990s was to come to understand that there are other ways for things to go wrong apart from viruses.

 

[Mithriel]

Free roaming bits of genetic material and the human genome what could go wrong

 

[rvallee]

We have known for decades. Nothing new here I am afraid. Hidden viruses were the explanation for everything when I was a kid sixty years ago.

People presenting with Long Covid symptoms have been assured, nay insisted, that it is impossible for this to happen, that if the virus is undetectable then it's gone and it's silly to worry about whether it could possibly ever linger around. Which we now know is possible, found so far in the gut, brain and nose.

More controversial but I think just as relevant, the same is said to Lyme patients who experience the same, it's simply silly to even entertain the idea that pathogens could possibly survive a round of antibiotics (nevermind... hell, microbiology and the whole antibiotic resistance thing... but also the fact that most infected with Lyme are never detected and thus not given antibiotics to begin with). The fact above is not just disputed but subject to outright mockery.

So as much as this is known, it is also considered laughable in fact when the possibility arises in individual cases. It's one of those weird things that everyone seems to know but is simply impossible. Which is really weird to be honest.

This may be common knowledge but it has many interpretations and in common practice it may as well not exist, as Long Covid has adeptly demonstrated yet again. Or it's very selectively true anyway.