What is it about?

Present throughout the rise and fall of every human conflict in history is another global conflict steadily drumming away in deep time; a battle of digital information much larger than 'fake news'. Like conflicts between great powers, the battle between host and virus is fueled by innovations on both sides engaged in an endless evolutionary 'arms race'. Although information is decisive in this battle, paradoxically, all viruses of greatest medical concern in recent years contain very little (e.g., HIV, dengue, zika, SARS, measles and influenza including avian H5N1). Due to a basic limit on the amount of information they can carry, these viruses are forced to use and distribute their information extremely efficiently. Here I coin “the information economy paradox” in virus evolution and discuss how this concept may pave the way for an entirely new approach to antiviral and immune therapies. ウイルスと宿主細胞は無限の進化的軍拡競争に従事しています。勝つように遺伝子的情報は重要ですが、アイズ、デンゲ熱、ジカ、サーズ、はしか、インフルエンザなどのRNAウイルスは逆説的に限定的なゲノムを持ちます。ウイルスの最強なポイントの一つは宿主細胞の多機能タンパク質を阻害することにより、細胞の免疫メカニズムおよび様々な機能を操ります。医薬の再目的化などの方法で、ウイルス進化の「最強なポイント」は「最弱なポイント」になることができると思います。本稿では、ウイルス進化に遺伝子の情報逆説を使うし、どうやって新しい療法を発明することが説明したい。

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Why is it important?

Our world faces many sustainability challenges. Increasingly, the development of new antiviral and immune medicines is one such challenge. These often need decades and hundreds of millions of dollars to bring to market. But viruses and cancers can pick up just a single mutation to render these useless, totally undermining this investment. Given the likely limits on future economic output due to the changing demographics of our society, I believe it is essential that we urgently develop treatments that break through the ‘impossible triangle’ of cost, effectiveness, robustness against mutant strains. I refuse to accept the alternatives: costlier and more limited access to future medicines, or negative impacts on health and longevity. 世界中にはたくさん持続可能性問題があります。ますます、新しい抗ウイルス医薬を開発するのが問題の一つです。なぜなら、一般的にそんなの医薬を開発するように、数十年かかって、数億ドルを使わなければなりません。しかし、ウイルスおよび癌は一度しかない変異することにより、医薬を役に立たなくし、この投資を早速に損なう可能性があります。さらに、変更している社会の人口動態の影響で、将来の経済発展が限定になっている。その効果、変異耐性で、安い治療を発明するのが必須だと思います。

Perspectives

It has long been said that the key to defeating a tough enemy is to creatively leverage his own strengths and turn them to our advantage. Viruses are excellent at making mutant versions of themselves, but this 'strength' comes with huge trade-offs. To remedy these, viruses manipulate the enormous amount of information already present in each of us. While effective in the short to medium term, nearly all current treatments ignore this fact and instead charge directly into the main strength of viruses. By both avoiding this trap and attacking around the softer flanks using host-oriented approaches, future treatments may be simultaneously highly effective, robust against mutant strains and far more cost-effective in the long term. But to achieve this, I want to encourage a fundamental shift in thinking around antiviral strategy.

Dr. Steven Heaton
RIKEN Center for Integrative Medical Sciences

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This page is a summary of: Harnessing host–virus evolution in antiviral therapy and immunotherapy, Clinical & Translational Immunology, January 2019, Wiley,
DOI: 10.1002/cti2.1067.
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