Functional Interaction of Nuclear Domain 10 and Its Components with Cytomegalovirus after Infections: Cross-Species Host Cells versus Native Cells

Ruth Cruz Cosme,Qiyi Tang,Francisco Puerta Martínez,Maria G Masucci

doi:10.1371/journal.pone.0019187

Ruth Cruz Cosme, Qiyi Tang + Show 2 more

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https://doi.org/10.1371/journal.pone.0019187

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Journal: PloS one	Publication Date: Apr 28, 2011
Citations: 62	License type: CC BY 4.0

Affiliation: Ponce Health Sciences University

Abstract

Species-specificity is one of the major characteristics of cytomegaloviruses (CMVs) and is the primary reason for the lack of a mouse model for the direct infection of human CMV (HCMV). It has been determined that CMV cross-species infections are blocked at the post-entry level by intrinsic cellular defense mechanisms, but few details are known. It is important to explore how CMVs interact with the subnuclear structure of the cross-species host cell. In our present study, we discovered that nuclear domain 10 (ND10) of human cells was not disrupted by murine CMV (MCMV) and that the ND10 of mouse cells was not disrupted by HCMV, although the ND10-disrupting protein, immediate-early protein 1 (IE1), also colocalized with ND10 in cross-species infections. In addition, we found that the UL131-repaired HCMV strain AD169 (vDW215-BADrUL131) can infect mouse cells to produce immediate-early (IE) and early (E) proteins but that neither DNA replication nor viral particles were detectable in mouse cells. Unrepaired AD169 can express IE1 only in mouse cells. In both HCMV-infected mouse cells and MCMV-infected human cells, the knocking-down of ND10 components (PML, Daxx, and SP100) resulted in significantly increased viral-protein production. Our observations provide evidence to support our hypothesis that ND10 and ND10 components might be important defensive factors against the CMV cross-species infection.

Highlights

Cytomegaloviruses (CMVs) are a b-subfamily of herpes viruses
The fact that CMV immediate-early protein 1 (IE1) disrupts the nuclear domain 10 (ND10) of native host cells supports the speculation that ND10 acts in a defensive capacity
The distribution of IE1 at the very early stage of infection was not different in cross-species infection compared with native infection (e.g., human CMV (HCMV) in human cells and murine CMV (MCMV) in mouse cells)

Summary

Introduction

Many types of cells (including fibroblast, epithelial, endothelial, and hematopoietic cells) are permissive for CMV infection, which infection results in the production of infectious particles [1], but CMV infection and replication are limited to a narrow host range [2,3]. SCMV productively infected human and monkey cells, but HCMV failed to replicate in monkey cells [3]. CMV replication in native host cells is a well-defined sequential process: entry into cells, immediate-early (IE) and early (E) gene expression, DNA replication, late gene expression, and viral production [6]. It has been determined that both CMV cross-species infections and low MOI (multiplicity of infection) infections in permissive cells are blocked at the post-entry level by intrinsic cellular defense mechanisms [3,6], but few details are known

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