Functional gap junction genes are encoded by insect viruses

Ichnoviruses belong to the virus family Polydnaviridae, whose members are obligately associated with certain endoparasitoid wasps. Expression of ichnovirus genes in parasitized lepidopteran hosts leads to immune suppression and is essential for successful parasitization. To date, the role of specific ichnovirus genes in alteration of host physiology has been unclear, and no cellular homologues have been described. Here, we describe the isolation of a gene family from two ichnoviruses that is homologous to the innexin gene family, which encodes gap junctions in invertebrates. Campoletis sonorensis ichnovirus (CsIV) innexins are expressed in multiple tissues in infected lepidopterans, including haemocytes, the primary immunocytes of the host. Two of the CsIV proteins have been expressed and shown to form functional gap junctions in Xenopus oocytes. To our knowledge this is the first study to describe gap junction genes in any virus. We hypothesize that the virus innexins disrupt cellular immunity in infected insects by altering normal gap junctional intercellular communication. This would represent a novel mechanism of viral alteration of host physiology, and suggests that gap junctions play a crucial role in coordinating cellular immune responses. Gap junctions, encoded by innexins in insects [1], coordinate multicellular processes. In insects, blood cells (haemocytes) play a critical role in immune responses and gap junctions are known to form between those cells [2,3], yet the functions of gap junctions in insect immunity are unclear. Pathogenic agents, such as polydnaviruses, may provide a tool to investigate their role in non-model systems. The virus family Polydnaviridae is unique in that its members, the ichnoviruses and bracoviruses, are obligately associated with parasitoid wasps [4]. Virions are delivered to host caterpillars during parasitization where virus-encoded transcripts and proteins are produced in the absence of virus replication [4]. In the case of ichnoviruses, virus-encoded proteins almost invariably suppress the immune system of the caterpillar, and thus are essential for successful parasitization (reviewed in [5]). Polydnavirus genomes are unusual in that they exhibit simultaneous reductive and proliferative evolution, i.e. few, if any, genes associated with virus replication and packaging are encapsidated, and the packaged genome contains genes generally associated with pathogenesis of the caterpillar host [5,6]. Therefore, genes identified in the ichnovirus genome may be assumed a priori both to be necessary for successful parasitization and to induce either immunological or developmental pathologies in the infected caterpillar. We identified five complete open reading frames in the genomes of two polydnaviruses, CsIV and …