Abstract
Numerous studies have shown that herpes simplex virus types 1 and 2 (HSVβ1, HSVβ2) are able to transform the morphological phenotype of rodent cells. Unlike other DNA tumor viruses the transformed cells did not consistently retain of express a given set of viral genes. In fact, transformation could be obtained using fragments of viral DNA that did not wholly encode viral proteins. Of interest within the transforming fragments were sequences which could assume a secondary structure like that of insertion elements. The failure to detect viral DNA in transformed cells led to the hitβandβrun hypothesis of HSV transformation. The mechanism by which HSV induces transformation is not understood. Various lines of investigation have shown that HSV is able to cause mutationsβboth point mutations and gene rearrangements. HSV is also able to induce gene amplification, particularly of sequences harboring an origin of replication such as SV40 or papillomaviruses. Other experiments have shown that HSV can activate the expression of endogenous type C retroviruses. More broadly, HSV has been shown to activate cellular transcription or to switch on the synthesis of host cell proteins not normally expressed in untransformed cells. the failure to detect viral DNA in a high proportion of human anogenital tumors made it difficult to implicate HSV in the etiology of those neoplasias, but it is consistent, however, with the observations on the mode of HSV transformation in vitro, and suggests that HSV could be involved in a multistage process of oncogenic transformation.