Constitutive and Inducible Innate Responses in Cells Infected by HSV-1- Derived Amplicon Vectors

Abstract

Amplicons are helper-dependent herpes simplex virus type 1 (HSV-1)-based vectors that can deliver very large foreign DNA sequences and, as such, are good candidates both for gene delivery and vaccine development. However, many studies have shown that innate constitutive or induced cellular responses, elicited or activated by the entry of HSV-1 particles, can play a significant role in the control of transgenic expression and in the induction of inflammatory responses. Moreover, transgene expression from helper-free amplicon stocks is often weak and transient, depending on the particular type of infected cells, suggesting that cellular responses could be also responsible for the silencing of amplicon-mediated transgene expression. This review summarizes the current experimental evidence underlying these latter concepts, focusing on the impact on transgene expression of very-early interactions between amplicon particles and the infected cells, and speculates on possible ways to counteract the cellular protective mechanisms, thus allowing stable transgene expression without enhancement of vector toxicity.

Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo

“…However, the oriLyt within amplicon vectors serves only to amplify the vector DNA for efficient packaging of a high number of vector copies into helper virus capsids via the pac signal [14] . Interestingly, the phenomenon of transgene silencing of amplicon vectors by HDAC-dependent mechanisms has also been described [55] . Whether or not the context of the oriLyt itself affects the level of gene expression has, to our knowledge, not been investigated.…”