Betaherpesviruses such as HCMV dramatically affect host cell physiology and encode a wide variety of functions that modulate the infected host cell as well as the immune response (Mocarski, 2002, 2004). Major structural and nonstructural proteins modulate host cell transcriptional repression (Saffert and Kalejta, 2006, Tavalai et al., 2006), cell-intrinsic responses (Abate et al., 2004; Goldmacher, 2004), responses to interferon (Child et al., 2004; Khan et al., 2004) and natural killer (NK) lymphocytes (Lodoen and Lanier, 2005), and adaptive antibody or T-lymphocyte immunity (Chapter 62). The host immune components that are targets of modulation by HCMV are the same host functions that are important in suppressing virus infection, suggesting that the balance between host clearance and viral escape mechanisms dictates many aspects of viral pathogenesis. By reducing the overall impact of antiviral defenses, HCMV seems to be able to escape the full brunt of host innate and adaptive immunity, thereby allowing the virus to persist. It now appears that an overwhelming majority of viral gene products are dedicated to modulation of host cell and immune modulation (Chapter 15). The overwhelming majority (∼100 gene products) may be implicated in modulation because they are dispensable for replication in cultured fibroblasts (Dunn et al., 2003; Yu et al., 2003).
During infection, HCMV and other cytomegaloviruses have a striking impact on cellular gene expression, cell cycle progression, and cellular behavior. More limited information suggests that roseolaviruses, HHV -6A, HHV -6B, and HHV -7 have a similar impact on cells (Chapters 18 and 47).