ABSTRACT
Replication
of human cytomegalovirus (CMV) depends on host cell gene products
working in conjunction with viral functions and leads to a dramatic
dysregulation of cell cycle gene expression. Comprehensive
transcriptional profiling was used to identify pathways most
dramatically modulated by CMV at late times during infection and to
determine the extent to which expression of the viral chemokine
receptor US28 contributed to modulating cellular gene expression. Cells
infected with the AD169 strain of virus or a fully replication
competent US28-deficient derivative (RV101) were profiled throughout
the late phase of infection (50, 72, and 98 h postinfection).
Although sensitive statistical analysis showed striking global changes
in transcript levels in infected cells compared to uninfected cells,
the expression of US28 did not contribute to these alterations. CMV
infection resulted in lower levels of transcripts encoding
cytoskeletal, extracellular matrix, and adhesion proteins, together
with small GTPases and apoptosis regulators, and in higher
levels of transcripts encoding cell cycle, DNA replication, energy
production, and inflammation-related gene products. Surprisingly, a
large number of cellular transcripts encoding mitosis-related proteins
were upmodulated at late times in infection, and these were associated
with the formation of abnormal mitotic spindles and the appearance of
pseudomitotic cells. These data extend our understanding of how broadly
CMV alters the regulation of host cell cycle gene products and
highlight the establishment of a mitosis-like environment in the
absence of cellular DNA replication as important for viral replication
and
maturation.
Global Analysis of Host Cell Gene Expression Late during Cytomegalovirus Infection Reveals Extensive Dysregulation of Cell Cycle Gene Expression and Induction of Pseudomitosis Independent of US28 Function
