How a little known virus can cause asthma in kids.

If I were a virus, I think I’d like to be Respiratory Syncytial Virus (RSV).

What is that, you ask? Exactly my point.

Our lungs are the only organ in our body that is exposed to the filth of our environment. Because of this, our lungs have to fight off bacteria, viruses and pollutants, and yet try to function normally to help us breathe. 

Asked to name a respiratory virus, our mind immediately jumps to influenza, the big daddy of viruses that affect our lung. Yet, there is a virus that infects more infants throughout the world (in developed and developing countries), that nearly all of us have been infected by at least once by the age of 1 year,  that we have no vaccine or treatment for, that our body is unable to develop long lasting immunity to, and that kills more elderly individuals than influenza. That virus is RSV, and yet, is but a blimp in our collective consciousness.

I will admit, I am partial to this virus. I work with it for my PhD. My aim is to study how infections with RSV early on can cause asthma.

Oh right. I forgot to tell you. If you are hospitalised with RSV infection as a kid, you have a higher likelihood of getting asthma as you get older. Influenza on the other hand? Can’t cause asthma.

See why I said I’d like to be RSV if I were a virus? Infectious, and yet staying under the radar.

There are a number of ways by which we think early life infection can cause asthma, and I might go into those in a later blog post. But one of the coolest suggestive mechanisms, was published by Nandini Krishnamoorthy, at the University of Pittsburgh and her colleagues in Nature Medicine in September, 2012.

 They started with the knowledge that in mice, any allergen, if given with TGFbeta (an important cytokine) to a baby mouse through its mother’s milk, then the baby mice develop tolerance to the allergen: by this, I mean that these baby mice will not have an asthmatic reaction to the same allergen as they get older. However, baby mice that received milk without the allergen would develop asthma if they saw the allergen later in life. This process is mediated by a subset of lymphocytes called T regulatory cells (Treg), which are important for tolerance and preventing autoimmune diseases.

Given this, Krishnamoorthy et al exposed new mouse moms to an allergen called OVA derived from eggs, so that these allergens are passed onto their pups through breast milk. These pups, when they were older, did have any asthmatic symptoms when exposed to OVA. However, the same pups, when infected with RSV virus and then exposed to OVA, developed severe asthmatic symptoms. Somehow, virus infection of these mice was breaking tolerance to the allergen, and causing disease.

How does the virus do this? Turns out, infection with the virus changes the nature of the cells in the lymph nodes of these tolerised pups, so that the Treg cells present are now Th2 expressing-Treg cells, rather than normal Treg cells. Th2 type immune responses have been shown to be crucial in mouse and humans for the development of asthma, and RSV’s ability to push Tregs down the Th2 path causes these cells to break their normal roles, and push towards asthma in mice.

What does RSV get out of this push towards an asthmatic-Th2 immune response? Both mouse and human babies (and probably babies of other species) have an immune response that starts off as Th2 biased. The reason this happens is because the alternative, a Th1 inflammatory response, while great for fighting off viruses as adults, also causes damage to normal cells and this would be bad for a still developing young baby. RSV has learnt to exploit this chink in our immune armour, and predominantly infects young children when their immune systems are still developing and are Th2 biased. This way, the virus can infect and replicate, before the Th1 immune response of our bodies evolve and stop the virus in its tracks. Additionally, there is some evidence that RSV actively induces a Th2 response, in order to carry along its merry way. Therefore, the virus doesn’t try to actively cause asthma— rather, it is the nature of our immune system, along with the viruses’s innate desire to live and replicate, that drives our immune system to develop asthma.

Not all kids who are infected however, get asthma. Why this happens, is a whole other mystery. Welcome to science.

Reference:

Krishnamoorthy et al. Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma. Nat Med. 2012 Oct;18(10):1525-30. doi: 10.1038/nm.2896. Epub 2012 Sep 9.