Do immunostimulatory defective viral genomes arise during natural infections? (49.16)

Abstract

Abstract The generation of defective viral genomes (DVGs) during the replication of viruses in vitro has been described for many different viruses including influenza, vesicular stomatitis and rabies. DVGs are truncated forms of the standard virus genome that are unable to replicate due to the lack of a functional viral polymerase. We have shown that DVGs have a potent ability to elicit the activation of dendritic cells in vitro demonstrating their exceptional capacity to trigger innate immunity. The presence of DVGs in viral preparations has been broadly correlated with protection against lethal doses of viruses. It was recently shown that RIG-I predominantly binds DVGs during infections with Sendai virus. The role of DVGs during natural infections is not known. Infection of bone marrow dendritic cells with different strains of Sendai virus showed that DVGs of different sizes are detected in all the viral preparations. In addition, infection with a Sendai virus strain that had been depleted of DVGs results in DVG generation at late points after infection correlating with the peak of viral replication. Interestingly, in mice infected with Sendai virus lacking DVGs we could also detect the appearance of DVGs at late times of infection. Together, these results show that DVGs can arise during the course of a natural virus infection stimulating exciting questions regarding their role stimulating anti-viral immune responses.