Human Cytomegalovirus UL131 Open Reading Frame Is Required for Epithelial Cell Tropism

Wang, Dai; Shenk, Thomas

doi:10.1128/jvi.79.16.10330-10338.2005

Cited by 330 publications

(382 citation statements)

References 41 publications

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“…Obviously, although other gene regions were also reported to contribute to EC tropism as evidenced by loss of EC tropism after deletion of the respective ORF (Dunn et al, 2003;Pretsch et al, 2005), changes due to cell culture adaptation apparently target preferentially the UL128-UL131A gene region. An explanation for this is provided by recent reports on the inhibition of virus release of strain AD169 after repair of a defective UL131A or insertion of an intact UL131A ORF (Adler et al, 2006;Wang & Shenk, 2005a). Loss of the protein complex formed by gH/gL and the pUL128-131A gene products obviously provides a growth advantage in fibroblasts at the cost of a restricted cell tropism.…”

Section: Discussionmentioning

confidence: 99%

Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E

Sinzger

Hahn

Digel

et al. 2008

Journal of General Virology

365

355

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Human cytomegalovirus (HCMV) strain TB40/E, replicates efficiently, exhibits a broad cell tropism and is widely used for infection of endothelial cells and monocyte-derived cells yet has not been available in a phenotypically homogeneous form compatible with genetic analysis. To overcome this problem, we cloned the TB40/E strain into a bacterial artificial chromosome (BAC) vector. Both highly endotheliotropic and poorly endotheliotropic virus clones, representing three distinct restriction fragment patterns, were reconstituted after transfection of BAC clones derived from previously plaque-purified strain TB40/E. For one of the highly endotheliotropic clones, TB40-BAC4, we provide the genome sequence. Two BACs with identical restriction fragment patterns but different cell tropism were further analysed in the UL128-UL131A gene region. Sequence analysis revealed one coding-relevant adenine insertion at position 332 of UL128 in the BAC of the poorly endotheliotropic virus, which caused a frameshift in the C-terminal part of the coding sequence. Removal of this insertion by markerless mutagenesis restored the highly endotheliotropic phenotype, indicating that the loss of endothelial cell tropism was caused by this insertion. In conclusion, HCMV strain TB40/E, which combines the high endothelial cell tropism of a clinical isolate with the high titre growth of a cell culture adapted strain, is now available as a BAC clone suitable for genetic engineering. The results also suggest BAC cloning as a suitable method for selection of genetically defined virus clones.

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Section: Discussionmentioning

confidence: 99%

Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E

Sinzger

Hahn

Digel

et al. 2008

Journal of General Virology

365

355

View full text Add to dashboard Cite

show abstract

“…HCMV glycoprotein H (gH) and glycoprotein L (gL) gene products can be incorporated into two different protein complexes involved in CMV infectivity: a glycoprotein O (gO)-containing complex known as gH/gL/gO and a complex containing UL128, UL130 and UL131 known as gH/gL/UL128-131. The UL131A-UL128 associates with gH and gL to produce a pentameric complex, gH/gL/UL131A-UL128, required for HCMV entry into ECs, epithelial cells, dendritic cells and macrophages (40)(41)(42)(43). In contrast, viral entry into fibroblasts have genetic determinants in complex gH/gL/gO (or gH/gL) in which HCMV glycoprotein gO coassociates with gH/gL and acts as a gH/gL chaperone (44).…”

Section: Variability Of CMV Strainsmentioning

confidence: 99%

“…These cellular specificities reside in the ULb' region in WT HCMV, and this region is deleted in laboratory strains; it contains factors that are not required for replication in fibroblasts but that are essential for EC infection (41,45). Repair of a mutated UL131 gene in the AD169 laboratory strain or in clinical isolates of HCMV restores the ability to infect and replicate in both epithelial cells and ECs but compromises the ability to replicate in fibroblasts (42).…”

Section: Variability Of CMV Strainsmentioning

confidence: 99%

The Cell Biology of Cytomegalovirus: Implications for Transplantation

Kaminski

Fishman

2016

American Journal of Transplantation

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Interpretation of clinical data regarding the impact of cytomegalovirus (CMV) infection on allograft function is complicated by the diversity of viral strains and substantial variability of cellular receptors and viral gene expression in different tissues. Variation also exists in nonspecific (monocytes and dendritic cells) and specific (NK cells, antibodies) responses that augment T cell antiviral activities. Innate immune signaling pathways and expanded pools of memory NK cells and cd T cells also serve to amplify host responses to infection. The clinical impact of specific memory T cell anti-CMV responses that cross-react with graft antigens and alloantigens is uncertain but appears to contribute to graft injury and to the abrogation of allograft tolerance. These responses are modified by diverse immunosuppressive regimens and by underlying host immune deficits. The impact of CMV infection on the transplant recipient reflects cellular changes and corresponding host responses, the convergence of which has been termed the "indirect effects" of CMV infection. Future studies will clarify interactions between CMV infection and allograft injury and will guide interventions that may enhance clinical outcomes in transplantation.

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“…A significant contribution to the development of a HCMV vaccine was the identification of the pentameric complex (PC), which consists of HCMV gH, gL, pUL128, pUL130 and pUL131 [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

Gerna

Revello

Baldanti

et al. 2017

Journal of General Virology

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Between the 1980s and 1990s, three assays were developed for diagnosis of human cytomegalovirus (HCMV) infections: leuko (L)-antigenemia, L-viremia and L-DNAemia, detecting viral protein pp65, infectious virus and viral DNA, respectively, in circulating leukocytes Repeated initial attempts to reproduce the three assays in vitro using laboratory-adapted strains and infected cell cultures were consistently unsuccessful. Results were totally reversed when wild-type HCMV strains were used to infect either fibroblasts or endothelial cells. Careful analysis and sequencing of plaque-purified viruses from recent clinical isolates drew attention to the ULb¢ region of the HCMV genome. Using bacterial artificial chromosome technology, it was shown by both gain-of-function and loss-of-function experiments that UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. In addition, a number of clinical isolates passaged in human fibroblasts had lost both properties (leuko-tropism and endothelial cell-tropism) when displaying a mutation in the UL131-128 locus

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Human Cytomegalovirus UL131 Open Reading Frame Is Required for Epithelial Cell Tropism

Cited by 330 publications

References 41 publications

Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E

Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E

The Cell Biology of Cytomegalovirus: Implications for Transplantation

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

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