Molecular Fordism: manufacturing a monster
Viruses are produced on an assembly line just like cars and laptops, and Ben Bleasdale is looking to throw a spanner in the works, as he explains in his article commended for the 2013 Max Perutz Science Writing Award.
Look at your phone on the desk next to you, perhaps the laptop you’re reading this on, maybe a car passing outside the window or a plane overhead. All these machines were made on a production line. Each one representing a list of components, assembled in a precise order to create a series of replicas — each machine becoming greater than the sum of its parts.
Viruses are molecular machines, likewise assembled from a list of parts pieced together in a specific order. Humans weren’t the first to recognise the potential of a production line to rapidly manufacture their Model T motorcars, Nature arrived at the solution first.
Embracing the ethos of mass production allows these infectious agents to rapidly clone themselves thousands of times, ultimately cannibalising their host cell in a relentless search for resources. Even for the simplest of viruses, each component must be manufactured at the right time and then precisely positioned in each infectious duplicate.
This miraculous transformation of molecular spare parts into beautifully-crafted viruses is being studied by researchers across the globe, probing for opportunities. Much as the proverbial “spanner in the works” can bring a production line grinding to a halt, a well-placed strike can likewise sabotage a virus infection. Many of our most successful anti-viral medicines work in this way, yet viruses are evolutionary acrobats and the search for the next target is perpetual.
My own research focuses on Herpes viruses, a vast family of microbes which infect virtually every animal on Earth — from humans to tortoises, oysters to whales. Once we’re infected, these viruses conceal themselves deep within our nervous system where they will remain for our entire lives. Unlike hit-and-run infections such as flu, these invaders become cohabiters in our own bodies, stalking us all the way to the grave.
This family is one of the most successful viruses on the planet, estimated to have infected 60-95 per cent of humans. Lurking within us for decades, it is known that Herpes viruses not only cause their own disease, but can also open the door to other infections such as HIV. Across the developing world, the spread of Herpes infections has become a major influence on the HIV epidemic. An effective treatment could therefore produce a domino effect across many diseases, and the assembly process is an ideal target for this intervention.
The entire construction of these infectious agents is dictated by their most important cargo — the genetic material residing at their core. Made of DNA, like our own genome, this set of blueprints details exactly how to manufacture the next wave of viruses. Surrounding this delicate DNA is a rigid shield, called a capsid. Made of perfectly interlocking pieces, this capsid bolts together to defend the genome from damage and detection during its onward journey.
At the next step of the production line, this capsid is coated in a layer of mass produced proteins — a molecular toolbox that will help the virus establish itself in the next host. Finally, at the end of the line, this entire assembled unit is wrapped in a membrane which will provide protection from the outside world. This membrane is studded with a constellation of molecular hooks that will specifically attach the virus to its next host, and help it force its way inside.
My research seeks to understand more about the carefully orchestrated process which brings these parts together, and how we might disrupt it. In the lab we can label individual parts with glowing tags, allowing us to observe new components being manufactured and sequentially assembled into developing viruses. High-powered electron microscopes let us peer deep inside infected cells, following the interactions on the assembly line at a molecular level — helping us piece together the story of viral mass production.
In addition to discovering more about the virus, we are simultaneously learning more about ourselves. Viruses manipulate, subvert and co-opt our cells into becoming factories for their own replication. This interaction can reveal secrets about our own biology too, both during health and disease. Armed with such knowledge, we are better prepared to tackle diseases caused by our own malfunctions, rather than just by infections. In this way viruses are great educators, teaching us as much about ourselves as we learn about them.
Ben is a PhD student at Imperial College London.