Elsevier

Experimental Cell Research

Volume 229, Issue 1, 25 November 1996, Pages 155-158
Experimental Cell Research

Short Note
The Nuclear Domain 10 (ND10) Is Disrupted by the Human Cytomegalovirus Gene Product IE1

https://doi.org/10.1006/excr.1996.0353Get rights and content

Abstract

The nuclear domain 10 (ND10) is modified during the life cycle of a number of viruses. In this study we report the effect of infection with human cytomegalovirus (HCMV) on the ND10 proteins PML, Sp100, and NDP52. Immunofluorescence analyses revealed that 1–2 h after infection (p.i.) with HCMV the immediate early gene (IE) products IE1 and IE2 transiently colocalize with ND10 proteins. At 4 h p.i. the IE gene products were distributed throughout the nucleus, which was accompanied by a complete disruption of ND10, affecting all analyzed proteins. Transfection studies using different HCMV-cDNA expression plasmids revealed that the expression of IE1 alone was sufficient to induce this disruption. As reported for other ND10-modifying viral proteins, no direct interaction between IE1 and the analyzed ND10 proteins could be detected. The disruption of ND10 by HCMV IE1 is very similar to that described for HSV-1 ICP0. Although there is no sequence similarity between proteins, this observation might suggest similar functions in virus–host interactions.

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    Another immediate early protein, IE2, is involved in activating gene transcription by directly interacting with the parental viral genome (Sourvinos et al., 2007). IE2-containing foci are frequently adjacent to ND10 (Ahn et al., 1998; Ahn and Hayward, 1997; Ahn et al., 1999; Korioth et al., 1996). However, a direct association between the viral genome and PML has not been reported, indicating that ND10 might be recruited towards pre-replication sites by recognizing a related protein instead of viral DNA.

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    PML-NBs increase in size and number in response to viral infection [17,18], and viral-associated interferon induction increases expression of PML [19] and Sp100 [20]. Studies from HSV-1 and HCMV indicate that viral genomes localize to PML-NBs after nuclear entry [21•,22], suggesting that PML-NBs act as a site where host antiviral resistance effectors confront incoming viral genomes. PML overexpression inhibits VZV infectivity [23•], PML and Sp100 knockdown rescues HSV-1 virus lacking ICP0 [24], and both PML and Daxx knockdown results in increased HCMV replication [25].

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