Evolutionary conflicts between viruses and restriction factors shape immunity

Key Points

• Restriction factors are cell-intrinsic genes expressed by the host that limit virus replication.

• Restriction factors are characterized by the rapid evolution of their coding sequences (under positive selection from virus infection), by their dedicated antiviral activity, by their usual induction by interferons (although this is not always the case), and by the presence of viral antagonists that neutralize their activity in some species.

• Several genetic mechanisms allow the host to keep pace with virus adaptations that enable the virus to evade restriction factors. These mechanisms include restriction factor heterozygosity, the duplication of restriction factor genes, and the limitation of viral evolution as a result of its effects on viral fitness.

• The evolution of restriction factors allows one to make inferences about ancient viruses and the selection pressure that they exerted on human ancestors.

• Because viruses evolve faster than their hosts, the innate immune system of modern-day vertebrates is generally optimized for past virus infections and not necessarily for the current viral threats in the modern world.

Abstract

The evolutionary 'arms race' between host restriction factors and viral antagonists has left a genetic 'signature' that can tell us much about the innate immune response to past and present viral infections.

Abstract

Host restriction factors are potent, widely expressed intracellular blocks to viral replication that are an important component of the innate immune response to viral infection. However, viruses have evolved mechanisms that antagonize restriction factors. Through evolutionary pressure for both host survival and virus replication, an evolutionary 'arms race' has developed that drives continuous rounds of selection for beneficial mutations in the genes encoding restriction factors and their viral antagonists. Because viruses can evolve faster than their hosts, the innate immune system of modern-day vertebrates is for the most part optimized to defend against ancient viruses, rather than newer viral threats. Thus, the evolutionary history of restriction factors might, in part, explain why humans are susceptible or resistant to the viruses present in the modern world.