Interferon-gamma-induced assembly block in the replication cycle of adenovirus 2: augmentation by tumour necrosis factor-alpha.

Replication of adenovirus 2 (Ad-2) is inhibited in A 549 cells pretreated with interferon-gamma (IFN-gamma). The antiviral effect is synergistically enhanced by the simultaneous presence of tumor necrosis factor-alpha (TNF-alpha) before infection. Under conditions of strong inhibition of virus progeny formation, viral DNA synthesis and [35S]methionine incorporation into most late viral proteins are only marginally impaired. Pulse chase experiments indicate a partial inhibition of processing of viral proteins. Viral proteins are not degraded and capsomeres accumulate in the inhibitor-treated cells. Capsid formation, on the other hand, is strongly inhibited in the cytokine-treated cells. The inhibition of Ad-2 replication in A 549 cells by IFN-gamma and TNF-alpha is caused, therefore, by a block in the maturation of Ad-2.