The virus within us

Evolution is a dance. And of all the dances in the world, perhaps it is most like a tango: intimate, and requiring continuous steps and counter-steps by the dancers.

Our dance through history with viruses has had its ups and its downs. Generally when you think of viruses you think of the COVID-19 pandemic, the long fight to eradicate smallpox, the deeply unpleasant rendezvous with the flu you had a few years ago. However, there is evidence that viruses have contributed extensively to who we humans are today - not only by shaping the history of human civilizations, but by literally shaping our genomes, from the inside.

This Microbial Mondays post is not about the viruses external to us - but rather about the viruses within us.

Within our very DNA.

I have written before on Microbial Mondays about retroviruses like HIV and HTLV, which are unique in that they make DNA from their own genetic material. Retrovirus genetics are written in a different type of molecule, called RNA. This construction of DNA from RNA is an incredible ability to work 'backwards'. The genetic blueprints for humans, as well as all other animals, are written in a 'DNA language', and our genetic information flows in one direction from DNA, to RNA, and finally to proteins. Retroviruses can subvert that. Having their own genetic code written as RNA means that upon infecting us, they can very quickly have our cells translate that RNA genome directly into protein for them (and making viral protein is necessary for making new virus). On top of that, the retroviruses will also work backwards, making their RNA into DNA, and then inserting it into our genome.

That's right, they literally copy themselves into our genetic code.

This process is a major reason why it is so difficult to find a true cure for HIV. Although the current treatments for HIV are highly effective, and can allow people to live a very normal life without ever progressing to AIDS, they are not curative. Once you have this retrovirus, you need to take medication to counteract the microbial intruder for the rest of your life. The genetic material of HIV will live on in your cells, hiding amongst the information for making human proteins, and as soon as you stop taking antiretroviral drugs the virus can start replicating again.

Although HIV-1 is a relatively new virus to humans - the first cases of human infection are thought to have happened around the beginning of the 20th century - humans have been living with retroviruses for a very long time. So long in fact, that a particularly intimate association between certain historical retroviruses and our own genome has developed. In simple terms, our genome has been colonized.

In modern humans, a large portion of our genome is actually composed of 'retroelements'. These retroelements are thought to have evolved from retroviruses that literally became part of us over time. The main difference between retroelements and retroviruses is that retroelements no longer move between different cells, like retroviruses do. They don't have that same viral life cycle of making more virus inside one cell, and then exiting the first cell to infect another one - hopscotching through your body, cell to cell. Retroelements still replicate, but the difference is that they stay within cells. From their steady home in our genome, they will replicate, making more of themselves, and then the progeny will head to a new home within our DNA. For this reason, if you take a close look at human DNA, there are many, many repeats of the same sequences. Little blips of retroelements scattered across our genome for all of time.

I'm part virus, anyways.

Whatever the reasons were for the colonization of human genomes by these historical retroviruses, getting rid of retroelements is no longer an option for us. They have become essential. Genes derived from retroelements are involved in core biological processes that make us who we are - such as placenta formation, cognitive functioning, and even immune defense . If these retroelements hadn't crept across and altered our genomes, we would not be who we are today.

For this reason, our immune system has developed a relatively peaceful relationship with retroelements. Although we do have some immune defenses dedicated to preventing excessive proliferation of retroelements , which could lead to excessive and unwanted mutations of essential genes, we do tolerate a low level of retroelement replication. On top of that, our immune system simply has to accept the retroelements that have already been inserted all over our DNA. Those retroelements are part of us now. We have adopted them, and they have adopted us. In short, we have learned to live with the virus within us.

Until next week,

Think outside the box, like viruses - they have many unexpected consequences.

~ Alex