Strategies for the identification and analysis of viral immune-evasive genes--cytomegalovirus as an example.

Co-evolution of herpesviruses with their hosts has resulted in multiple interactions between viral genes and cellular functions. Some interactions control genomic maintenance and replication in specific tissues, other affect the immune control at various stages. Few immunomodulatory functions of genes can be predicted by sequence homology. The majority of genes with immunomodulatory properties only become apparent in functional assays. This chapter reviews procedures which have been used for successful identification of immunomodulatory genes in the past and deals with recent methods which may be applicable for the identification of additional immunomodulatory functions unknown so far.

The Pristionchus HOX gene Ppa-lin-39 inhibits programmed cell death to specify the vulva equivalence group and is not required during vulval induction.

In the two nematode species Caenorhabditis elegans and Pristionchus pacificus the vulva equivalence group in the central body region is specified by the Hox gene lin-39. C. elegans lin-39 mutants are vulvaless and the vulval precursor cells fuse with the surrounding hypodermis, whereas in P. pacificus lin-39 mutants the vulval precursor cells die by apoptosis. Mechanistically, LIN-39 might inhibit non-vulval fate (cell fusion in C. elegans, apoptosis in P. pacificus), promote vulval fate or do both. To study the mechanism of lin-39 function, we isolated P. pacificus cell death mutants and identified mutations in ced-3. Surprisingly, P. pacificus ced-3; lin-39 double mutants form a functional vulva in the absence of LIN-39 activity. Thus, in P. pacificus lin-39 specifies the vulva equivalence group by inhibiting programmed cell death. Furthermore, these data reveal an important difference in a later function of lin-39 between the two species. In C. elegans, LIN-39 specifies vulval cell fates in response to inductive RAS signaling, and in P. pacificus LIN-39 is not required for vulval induction. Thus, the comparative analysis indicates that lin-39 has distinct functions in both species although the gene is acting in a homologous developmental system.