Fundamentals of the Host-Virus Evolutionary Arms Race

Abstract

The immune system has been battling viral infections over the course of millions of years in primate evolution. The constant evolution of hosts and viruses to defeat the other has led to a high stakes genetic arms race. Here I present a detailed study of three antiviral proteins locked in antagonistic viral conflict called Tetherin, Viperin and SAMHD1. Using a combined approach of virology and evolutionary biology, I have reconstructed their evolutionary arms race between primates and lentiviruses, including HIV-1, HIV-2 and related SIVs. The broad themes that emerge from my research are two-fold. First, lentiviruses are able to evolve new functions within existing gene repertoires to counteract rapidly evolving host antiviral genes. Second, hosts escape from viral pressure either by single amino acid changes or by deletions of a `susceptibility domain'. Thus, my thesis research has helped define the rules by which host-virus arms races ensue. Based on my findings, we contend that the host evolutionary framework is a fundamental pillar of antiviral restriction.