Catharina Svensson research group

Adenovirus type 12 induced interferon response

Adenovirus expresses a multitude of regulatory proteins to ensure efficient replication during a lytic virus infection. The immediate early E1A gene encodes two primary regulators, which are essential for transcriptional activation and forced entry of the host cell into the S-phase and for blocked induction of interferon (IFN) and IFN signalling. Despite many similarities, non-oncogenic and highly oncogenic adenovirus demonstrate differences in their productivity and cytopathic activity, where the highly oncogenic Ad12 is less virulent and shows significantly less impact on host cell gene expression compared to the non-oncogenic Ad2. We have recently shown that Ad12 induces a specific activation of the IFN pathway during the later stage of infection. The inability of Ad2 to completely evade the first line antiviral defence might explain the relatively low virulence of this virus compared to AdV2, but an inadequate expropriation of the biosynthetic machinery of the host cell is also likely to play an important role. Since the E1A is highly conserved between different adenovirus serotypes the underlying mechanism(s) might be differences in late gene expression or modulation of E1A activities during the late phase. This will be determined by a temporal analyse of the E1A expression of Ad12 as well as the possibility that the altered association between E1A and p300 – compared to Ad2 E1A - interferes with the inhibition of JAK/STAT-signalling. In addition, Ad2 express two different VA RNA genes; VA RNAI, which have a prime function in blocking the IFN induced antiviral protein PKR and VA RNAII, which is involved in miRNA regulation. Thus the single VA RNA of Ad12 might be inadequate to support efficient conditions for virus replication. Finally, part of the IFN response engages the nuclear POD structures, which are reorganised during a Ad2 infection by proteins encoded by the E4 region. Whether Ad12 has homologous activities are unknown.