Viral Vector: Biochemistry Arcade

Infected cells act as decoys for the antibodies, which gives you a moment to breathe. Infect enough of them and a boss cell appears. On Easy, every boss cell is a puzzle about viruses and our defences, with nothing to read; on Medium and Hard, it asks a question, and if you’re stuck you can play a puzzle for a clue. Each level brings the next puzzle. A wrong answer costs a life; on Medium, an answer without a clue wins one back, and on Hard there are no lives back.

The science

• You are a virus. Viruses can’t copy themselves on their own: they enter a host cell and use its machinery to make new virus particles (viral replication).
• The shell. A virus wraps its genome in a protein shell, the capsid, often built from many copies of one protein. With Jade Forwood’s group we solved the capsid of beak and feather disease virus, which kills parrots and cockatoos: 60 copies of one protein, arranged as twelve rings of five.
• The antibodies. Antibodies are Y-shaped proteins made by B cells. They bind to a virus and can stop it entering cells.
• The puzzles. A virus gets into a cell through a receptor that fits its spike: the spike of SARS-CoV-2 binds ACE2. Infected cells spot viral RNA with sensors such as RIG-I, which pass the message through MAVS and IRF3 to the nucleus, and the cell sends out interferon to warn its neighbours; some viruses block that chain, such as Hendra virus with its W protein (see the Hendra and Nipah W proteins with importin α). Viruses change a little as they copy themselves (antigenic drift), which is why the flu vaccine is updated every year, and a vaccine trains the immune system to make antibodies before the real virus arrives.
• The quiz covers viruses and immunity (antibiotics, antigens, vaccines, cytotoxic T cells, interferon, ACE2) and enzymes (lock and key and induced fit, pepsin, amylase), haemoglobin, rhodopsin, the Bcl-2 family and apoptosis, kinesin, the nuclear localisation signal, the electron transport chain and ATP synthase. I helped with a crystal structure of part of ATP synthase: see F1-ATPase.

Where the game cuts corners

• Viruses can’t steer or swim: they drift with whatever fluid they’re in until they bump into a cell with the right receptor on its surface.
• Infected cells don’t act as decoys. In life, they’re found and destroyed by cytotoxic T cells and natural killer cells; in the game, the antibodies chase them instead.
• Receptors aren’t shaped like stars and squares, and a virus doesn’t swap its spikes for new ones: changes come from copying mistakes (mutations), and the viruses that antibodies no longer recognise are the ones that spread.
• Nobody fetches a capsid’s pieces: copies of the protein find each other and click together on their own (self-assembly).
• There are no boss cells, and as far as anyone knows, no virus has ever answered a biochemistry question.