Suppression of high mobility group protein T160 expression impairs mouse cytomegalovirus replication

The high mobility group (HMG-1) box proteins bind both non-B-DNA conformations and specific nucleotide sequences. They have been implicated in a wide variety of cellular functions involving DNA, such as transcription, replication and recombination. To determine whether HMG-1 box protein T160 plays a role in virus replication, we employed an antisense strategy to inhibit its expression in NIH 3T3 cells. The two T160 clones that expressed levels of T160 50% lower than those expressed by clones transfected with the empty vector (Neo+ clones) were investigated with respect to their permissiveness to the growth of viruses representing three families: Rhabdoviridae, vesicular stomatitis virus (VSV); Picornaviridae, encephalomyocarditis virus (EMCV), and Alpha- and Betaherpesviridae, herpes simplex virus 1 (HSV-1) and mouse cytomegalovirus (MCMV), respectively. They displayed a high degree of resistance to MCMV replication, but were fully permissive to the other viruses. Competitive PCR and probing IE-1 products by Western blot analysis showed that this resistance was not due to depressed levels of virus adsorption during the early phases of infection. We therefore conclude that T160 is involved in replication of the betaherpesvirus MCMV.