Worming into the cell: Viral reproduction in Caenorhabditis elegans

Abstract

Viruses, which infect a myriad of cell types from bacteria to mammalian cells, are the ultimate parasites. Upon infection of a host cell, these entities replicate their genetic material, express the proteins required to form mature viral particles, and exit the cell to initiate a subsequent round of infection. At all of these stages, viruses rely heavily on host resources and factors. It is, therefore, not surprising that the study of viral life cycles has contributed enormously to our understanding of basic cellular physiology. Furthermore, virus-induced diseases are perhaps the most prevalent pathological states in human beings; thus, understanding virus interactions with the human host has had an important medical impact. Much of our understanding of viral reproduction comes from genetic studies of virus–host interactions. For example, genetic analysis has proven to be a powerful tool for studying virus (phage)–host interactions in bacteria. Mutants of both phage and their host bacteria have allowed detailed understanding of the functions of phage genes, the functions of host factors hijacked by the phage, and the host defenses that inhibit phage reproduction (1). Genetic analysis has been similarly informative in analyzing the interactions between viruses and their plant hosts (2). The story is significantly different in animals, however, where genetic studies of virus–host interactions have generally been one-sided, focusing principally on the viral genome. Although human and murine mutations affecting various aspects of virus–host interactions have been described (3), a systematic, unbiased genetic approach to studying such interactions in these systems has not been possible. Natural viruses that attack the fruit fly Drosophila melanogaster exist, and a systematic genetic dissection of Drosophila C virus replication in cultured cells has been published recently (4); however, although some of the requirements for C virus to infect WT flies have been characterized (5), replication of these viruses in living animals has not been extensively studied. A natural virus for the nematode Caenorhabditis elegans has not been described; thus, until recently, this organism was not considered an appropriate model organism for studying virus–host interactions. However, the situation may be about to change. A series of articles published over the past few months, including an article by Liu et al. (6) in this issue of PNAS, now demonstrates that viruses that infect mammalian cells can infect, replicate, and assemble within C. elegans cells (7–9). These advances suggest that C. elegans could become an important system for understanding basic aspects of virus–host interplay.