Hantaviruses and innate immunity

Hantaviruses of the family Hantaviridae are enveloped viruses with a three-segmented negative-sense RNA genome that are found worldwide in rodents and other small mammals. While the persistent infection of the reservoir host is predominantly asymptomatic, many hantaviruses can cause severe disease after zoonotic transmission to humans, such as hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus-induced (cardio-) pulmonary syndrome (HCPS) in the Americas. The severity of the disease is probably dependent on the interaction between the particular virus and the hosts' innate immune response. Innate immunity represents an initial barrier against invading pathogens and enables non-specific detection and control of the infection via evolutionary conserved patterns and mechanisms. While hantaviruses are capable of effective inhibition or evasion of these mechanisms in their respective reservoir host, this evolutionary adaption is lacking following infection of other hosts such as humans. As a consequence, a pronounced immune response is induced, which ultimately leads to virus clearance, but also plays a crucial role in hantavirus-induced vascular pathogenesis. The question of how hantavirus replication activates innate immunity, by which mechanisms the viruses counteract it and how the antiviral immune response affects virus replication and the homeostasis of infected tissues is therefore crucial to understanding the pathogenesis of hantaviruses. Since their discovery in 1976, numerous interactions between hantaviruses and the innate immune response have been identified. However, many questions remain unanswered, particularly with regard to the molecular mechanisms of immune activation in different host species and the differences between high and low pathogenic hantaviruses.