More recently, the Brune group isolated a naturally acquired mutant MCMV that was able to replicate rapidly and to high titers in human retinal pigment epithelial cells. The interesting observation that the ability of mutated MCMV to disrupt ND10 seems to be related to viral production initiated our investigation on whether the disruption of ND10 might be related to HCMV TC-SP 14 infection in mouse cells. In the present study, we discovered that HCMV infection in mouse cells can express IE and many early genes and is blocked before DNA replication. In addition, we show that ND10 colocalizes with IE1 in cross-species infections but is not dispersed by CMV in such infections and that ND10 components are involved in blocking viral gene expression in both MCMV and HCMV cross-species infections. In recent years, nuclear domain 10, also called PML bodies, has been a topic of intense interest, especially in terms of its role in viral infection. Although a great deal of evidence supports the theory that ND10 components such as PML, Daxx, and SP100 are viral gene repressors and protect host cells against many viruses, the effects of the ND10 structure on viral infection have been not determined. The fact that several herpesviruses are able to disrupt ND10 at a very early stage of infection implies that ND10 has a defensive role in the process. However, several DNA viruses dock their input DNA, replicate DNA, and transcribe immediateearly genes at ND10, which argues that ND10 favors viral replication. To TASP 0390325 comparatively investigate the roles of ND10 and ND10 proteins in cross-species infections, we performed an immunofluorescence assay to detect the effects of CMV infection on ND10. We discovered that during the infection of MCMV in human cells, MCMV IE1 distributed both diffusely and as domains, which differs from what has been found in mouse cells, where IE1 distributes only diffusely. In addition, MCMV IE1 loses the ability to disrupt the ND10 of human cells. HCMV IE1 also loses the ability to disperse mouse cell ND10. Previously, it was found that laboratory strains of HCMV infection in mouse cells can express only IE1 and not IE2, even though that IE1 shares a promoter and its first three exons with IE2. Therefore, it was concluded that HCMV infection in mouse cells was blocked at the IE stage. However, it has been reported that the laboratory strains of HCMV experience profound mutations during replication in human fibroblast cells. The mutations lead not only to the attenuation of HCMV but also to the narrowing of cell tropisms. The mutation of HCMV cell tropism occurred at gene UL128�C131 since the repaired UL128�C131 caused the recovery of cell tropisms.