title: The susceptibility of primary cultured rhesus macaque kidney epithelial cells to rhesus cytomegalovirus strains.
abstract: Kidney epithelial cells are common targets for human and rhesus cytomegalovirus (HCMV and RhCMV) in vivo, and represent an important reservoir for long-term CMV shedding in urine. To better understand the role of kidney epithelial cells in primate CMV natural history, primary cultures of rhesus macaque kidney epithelial cells (MKE) were established and tested for infectivity by five RhCMV strains, including two wild-type strains (UCD52 and UCD59) and three strains containing different coding contents in UL/b'. The latter strains included 180.92 [containing an intact RhUL128-RhUL130-R hUL131 (RhUL128L) locus but deleted for the UL/b' RhUL148-rh167-loci], 68-1 (RhUL128L-defective and fibroblast-tropic) and BRh68-1.2 (the RhUL128L-repaired version of 68-1). As demonstrated by RhCMV cytopathic effect, plaque formation, growth kinetics and early virus entry, we showed that MKE were differentially susceptible to RhCMV infection, related to UL/b' coding contents of the different strains. UCD52 and UCD59 replicated vigorously in MKE, 68-1 replicated poorly, and 180.92 grew with intermediate kinetics. Reconstitution of RhUL128L in 68-1 (BRh68-1.2) restored its replication efficiency in MKE as compared to UCD52 and UCD59, consistent with the essential role of UL128L for HCMV epithelial tropism. Further analysis revealed that the UL/b' UL148-rh167-loci deletion in 180.92 impaired RhUL132 (rh160) expression. Given that 180.92 retains an intact RhUL128L, but genetically or functionally lacks genes from RhUL132 (rh160) to rh167 in UL/b', its attenuated infection efficiency indicated that, along with RhUL128L, an additional protein(s) encoded within the UL/b' RhUL132 (rh160)-rh167 region (potentially, RhUL132 and/or RhUL148) is indispensable for efficient replication in MKE.
authors.affiliation: Center for Comparative Medicine, University of California, Davis, CA, USA.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Department of Immunology, Tulane National Primate Research Center, Tulane University, Covington, LA, USA.
authors.forename: Amitinder
authors.initials: A
authors.lastname: Kaur
authors.affiliation: Hookipa Biotech AG, Helmut-Qualtinger-Gasse 2, Vienna, Austria.|Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Anders
authors.initials: A
authors.lastname: Lilja
authors.affiliation: Division of Translational Vaccine Research, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Walter
authors.affiliation: Center for Comparative Medicine, University of California, Davis, CA, USA.|Department of Pathology and Laboratory Medicine, University of California, Davis, CA, USA.|California National Primate Research Center, University of California, Davis, CA, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Barry
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000254:growth & development* / Q000502:physiology; D003588:Cytopathogenic Effect, Viral; D004847:Epithelial Cells / Q000821:virology*; D007668:Kidney / Q000166:cytology*; D008253:Macaca mulatta / Q000821:virology*; D010948:Viral Plaque Assay; D053586:Virus Internalization; D014779:Virus Replication