Evolutionarily conserved herpesviral protein interaction networks.

Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV).

Herpesviral protein networks and their interaction with the human proteome.

The comprehensive yeast two-hybrid analysis of intraviral protein interactions in two members of the herpesvirus family, Kaposi sarcoma-associated herpesvirus (KSHV) and varicella-zoster virus (VZV), revealed 123 and 173 interactions, respectively. Viral protein interaction networks resemble single, highly coupled modules, whereas cellular networks are organized in separate functional submodules. Predicted and experimentally verified interactions between KSHV and human proteins were used to connect the viral interactome into a prototypical human interactome and to simulate infection.

Cloning of the genomes of human cytomegalovirus strains Toledo, TownevarRIT3, and Towne long as BACs and site-directed mutagenesis using a PCR-based technique.

The 230-kb human cytomegalovirus genome is among the largest of the known viruses. Experiments to determine the genetic determinants of attenuation, pathogenesis, and tissue tropism are underway; however, a lack of complete sequence data for multiple strains and substantial problems with genetic instability during in vitro propagation create serious complications for such studies. For example, recent findings suggest that common laboratory strains Towne and AD169 passaged in cultured human fibroblasts are missing up to 15 kb of genetic information relative to clinical isolates.