Mighty mice meet their match

The problem
IT’S AN EVOLUTIONARY arms race out there. Viruses that infect organisms evolve to evade the immune systems of their hosts. Every time that happens, host animals like us must create strategies to battle the infections and diseases they cause.
For example, retroviruses are a family of viruses that have an RNA genome. While it’s often said that the fundamental building block of life is DNA, the genetic material of these viruses is RNA. Retroviruses produce DNA from their RNA and insert it into a host’s genome, changing the host forever. From then on, the virus replicates with the host cell’s DNA.
Our immune system protects us against most retroviruses. Only the human immunodeficiency virus (HIV) and the human T-lymphotropic virus (HTVL) have been shown to cause diseases in humans. Both have evolved ways to get around our immune defences.

The researcher
Marc-Andre Langlois does his research for the Faculty of Medicine at Roger Guindon Hall on the General Hospital Campus. He studies how retroviruses replicate and infect cells—specifically how cells are able to protect themselves against retroviruses.

The project
One of the best armaments our cells have is a family of proteins called APOBEC3. It’s still a mystery how they do it, but APOBEC3 proteins can completely deactivate all retroviral invaders by mutating the attacking DNA before it can be inserted into the host’s genome. The exceptions are HIV and HTVL. Those two have out evolved our protein parapets.
While primates have seven APOBEC3 proteins, mice have only one. This really interests Langlois. The mice APOBEC3 protein is more general than any of our seven. However, even mice can be infected by retroviruses. One of their versions of HIV is called AKV.

The key
Langlois was able to observe the arms race between AKV and the mouse APOBEC3 protein. Mice with diverse abundances of APOBEC3 were better at restricting AKV than mice with any specific form of APOBEC3. They can mutate (and so deactivate) more variations of the retrovirus. Langlois concludes that, since APOBEC3 stops infections by mutating the attackers, it pressures AKV to evolve. Because the mice’s own weapons against AKV cause it to mutate at an exaggerated rate, a broad set of deterrents provides for the best defense against such a varied viral foe.