Host-virus interactions and defense mechanisms for giant viruses

Giant viruses, with virions larger than 200 nm and genomes larger than 340 kilobase pairs, modified the now outdated perception of the virosphere. With virions now reported reaching up to 1.5 μm in size and genomes of up to 2.5 Mb encoding components shared with cellular life forms, giant viruses exhibit a complexity similar to microbes, such as bacteria and archaea. Here, we review interactions of giant viruses with their hosts and defense strategies of giant viruses against their hosts and coinfecting microorganisms or virophages. We also searched by comparative genomics for homologies with proteins described or suspected to be involved in defense mechanisms. Our search reveals that natural immunity and apoptosis seem to be crucial components of the host defense against giant virus infection. Conversely, giant viruses possess methods of hijacking host functions to counteract cellular antiviral responses. In addition, giant viruses may encode other unique and complex pathways to manipulate the host machinery and eliminate other competing microorganisms. Notably, giant viruses have evolved defense mechanisms against their virophages and they might trigger defense systems against other viruses through sequence integration. We anticipate that comparative genomics may help identifying genes involved in defense strategies of both giant viruses and their hosts.