Abstract
PURPOSE: The earliest host-virus interactions occur during virus attachment and entry into cells. These initial steps in the virus lifecycle influence the outcome of infection beyond delivery of the viral genome into the cell. Herpesviruses alter host signaling pathways and processes during attachment and entry to facilitate virus infection and modulate innate immune responses. We suggest in this review that understanding these early signaling events may inform the rational design of therapeutic and prevention strategies for herpesvirus infection, as well as the engineering of viral vectors for immunotherapy purposes. RECENT FINDINGS: Recent reports demonstrate that modulation of Herpes Simplex Virus Type-1 (HSV-1) entry results in unexpected enhancement of antiviral immune responses. SUMMARY: A variety of evidence suggests that herpesviruses promote specific cellular signaling responses that facilitate viral replication after binding to cell surfaces, as well as during virus entry. Of particular interest is the ability of the virus to alter innate immune responses through these cellular signaling events. Uncovering the underlying immune evasion strategies may lead to the design of live-attenuated vaccines that can generate robust and protective anti-viral immune responses against herpesviruses. These adjuvant properties may be extended to a variety of heterologous antigens expressed by herpesviral vectors.