A cyclooxygenase-2 homologue encoded by rhesus cytomegalovirus is a determinant for endothelial cell tropism.
Cyclooxygenase-2 (COX-2) is a cellular enzyme in the eicosanoid synthetic pathway that mediates the synthesis of prostaglandins from arachidonic acid. The eicosanoids function as critical regulators of a number of cellular processes, including the acute and chronic inflammatory response, hemostasis, and the innate immune response. Human cytomegalovirus (HCMV), which does not encode a viral COX-2 isoform, has been shown to induce cellular COX-2 expression. Importantly, although the precise role of COX-2 in CMV replication is unknown, COX-2 induction was shown to be critical for normal HCMV replication. In an earlier study, we identified an open reading frame (Rh10) within the rhesus cytomegalovirus (RhCMV) genome that encoded a putative protein (designated vCOX-2) with high homology to cellular COX-2. In the current study, we show that vCOX-2 is expressed with early-gene kinetics during RhCMV infection, resulting in production of a 70-kDa protein. Consistent with the expression of a viral COX-2 isoform, cellular COX-2 expression was not induced during RhCMV infection. Finally, analysis of growth of recombinant RhCMV with vCOX-2 deleted identified vCOX-2 as a critical determinant for replication in endothelial cells.
Rue
Cary A
CA
Department of Molecular Microbiology and Immunology, 3181 SW Sam Jackson Road, Oregon Health Sciences University, Portland, OR 97239, USA.
Jarvis
Michael A
MA
Knoche
Amber J
AJ
Meyers
Heather L
HL
DeFilippis
Victor R
VR
Hansen
Scott G
SG
Wagner
Markus
M
Früh
Klaus
K
Anders
David G
DG
Wong
Scott W
SW
Barry
Peter A
PA
Nelson
Jay A
JA
D000595:Amino Acid Sequence; D000818:Animals; D051546:Cyclooxygenase 2; D003587:Cytomegalovirus / Q000201:enzymology* / Q000235:genetics; D042783:Endothelial Cells / Q000821:virology*; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D008253:Macaca mulatta / Q000821:virology*; D008969:Molecular Sequence Data; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000502:physiology*; D018523:Tropism; D014764:Viral Proteins / Q000502:physiology*; D014779:Virus Replication
D007527:Isoenzymes; D014764:Viral Proteins; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases