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Human cytomegalovirus (HCMV) causes a broad spectrum of clinical manifestations in immunocompromised patients, including infection of the gastrointestinal tract. To investigate the role of epithelial cells in the gastrointestinal HCMV disease, we used the intestinal epithelial cell line Caco-2, which is permissive for HCMV replication. In differentiated Caco-2 cells, we showed previously that HCMV...
The human cytomegalovirus (HCMV) UL112–113 gene products play important roles in viral DNA replication and transcriptional regulation. In this report, we characterize two novel transcripts originating from the homologous M112–113 (e1) region of the murine cytomegalovirus (MCMV) genome. These transcripts of 2.0 and 2.4 kb represent alternatively spliced products of the e1 gene region. Analysis of the...
Similar to other herpesviruses, human cytomegalovirus remains in the infected host following resolution of the primary infection. The ability to persist in the host after primary infection is believed to be strongly influenced by the ability of HCMV to down-regulate immune recognition of infected cells. One of the genes contributing to immune evasion is the US3 gene. The US3 gene has been shown to...
The human cytomegalovirus (HCMV) UL57 gene lies adjacent to HCMV oriLyt, from which it is separated by an organizationally conserved, mostly noncoding region that is thought to both regulate UL57 expression and activate oriLyt function. However, the UL57 promoter has not been studied. We determined the 5' ends of UL57 transcripts toward an understanding of the potential relationship between UL57 expression...
Human cytomegalovirus (CMV) genes UL36 and UL37 encode viral inhibitor of caspase-8-induced apoptosis (vICA) and viral mitochondria inhibitor of apoptosis (vMIA), respectively. Rhesus macaque CMV homologues, denoted Rh-vICA and Rh-vMIA, were identified and found to suppress apoptosis. One of these functions was conserved in MCMV, encoded by the M36 gene and denoted M-vICA. Conserved regions were compared...
Previously, we identified the glycoprotein gO gene, UL74, as a hypervariable locus in the human cytomegalovirus (HCMV) genome [Virology 293 (2002) 281]. Here, we analyze gO from 50 isolates from congenitally infected newborns, transplant recipients, and HIV/AIDS patients from Italy, Australia, and UK. These are compared to four gO groups described from USA transplantation patients [J. Virol. 76 (2002)...
The carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAP II) ordinarily exists in electrophoretically distinct hypophosphorylated and hyperphosphorylated forms. Human cytomegalovirus infection induced forms of this subunit whose electrophoretic mobilities were intermediate without decreases in abundance of the original forms. Phosphatase treatment nearly eliminated the...
The virally encoded chemokine receptors US28 from human cytomegalovirus and ORF74 from human herpesvirus 8 are both constitutively active. We show that both receptors constitutively activate the transcription factors nuclear factor of activated T cells (NFAT) and cAMP response element binding protein (CREB) and that both pathways are modulated by their respective endogenous receptor ligands. By addition...
HIV-infected patients on highly active antiretroviral therapy (HAART) have persistently decreased cytomegalovirus (CMV)-specific proliferative responses [lymphocyte proliferation assay (LPA)] in spite of increases in CD4+ T cell counts. Here we demonstrate an association between apoptosis of unstimulated peripheral blood mononuclear cells (uPBMC) and decreased CMV-LPA. HAART recipients had more apoptosis...
CD13/aminopeptidase N is a membrane-bound metalloproteinase implicated in human cytomegalovirus (HCMV) infection and pathogenesis. Anti-CD13 antibodies can neutralize HCMV infectivity, and HCMV viremia after bone marrow transplantation induces anti-CD13 autoantibodies which correlate with development of chronic graft vs. host disease. We examined whether murine CD13/APN was similarly implicated in...
HIV-infected patients fail to fully recover cell-mediated immunity despite HAART. To identify regulatory factors, we studied the phenotype and function of in vitro cytomegalovirus (CMV)-stimulated T cells from HAART recipients. CFSE-measured proliferation showed CD4 + and CD8 + cells dividing in CMV-stimulated cultures. Compared with healthy controls, CMV-stimulated lymphocytes from...
Human cytomegalovirus (HCMV; Human herpesvirus 5) and the other betaherpesviruses encode a number of distinct gene families, including the US12 family, which is represented only in the cytomegaloviruses of higher primates, and is comprised of a set of 10 contiguous genes (US12 through US21), each encoding a seven-transmembrane (7TM) protein. Nonessential for replication in cell culture but well-conserved...
The human cytomegalovirus (HCMV) US12 gene family is a group of 10 predicted seven-transmembrane domain proteins that have some features in common with G-protein-coupled receptors. Little is known of their patterns of expression, localization, or functional interactions. Here, we studied the intracellular localization of three US12 family members, US14, US17, and US18, with respect to various intracellular...
An AT-rich region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region (UR). It has been shown that the UR represses activation of transcription from the UL127 promoter and functions as a boundary between the divergent UL127 and MIE genes during human CMV infection [Angulo, A., Kerry, D., Huang,...
Functional immune reconstitution is limited after HAART, maintaining the interest in adjunctive immune-modulators. We compared in vitro the effects of the γ-chain T-cell growth cytokines IL-2, IL-4, IL-7 and IL-15 on cytomegalovirus-stimulated cell-mediated immunity. IL-2 and IL-15 increased cytomegalovirus-specific lymphocyte proliferation in HAART recipients, whereas IL-4 and IL-7 did not. The boosting...
Human cytomegalovirus (HCMV) viral chemokine, UL146, and TNF α-like receptor UL144 genes show a high degree of hypervariability in clinical isolates. These proteins are predicted to be immune modulators and may contribute to the pathogenesis of HCMV infections. We analyzed the UL146 and UL144 genetic variation of 51 HCMV isolates from congenitally infected children and 13 isolates from children in...
Guinea pig cytomegalovirus (GPCMV) provides a useful model for studies of congenital CMV infection. During characterization of the GPCMV genome sequence, we identified two types of strains in a virus stock purchased from ATCC. One of them, GPCMV/del, lacks a 1.6 kb locus that positionally corresponds to murine CMV (MCMV) M129–M133. Growth of GPCMV/del in cell culture was marginally better than that...
While the importance of cellular and viral kinases in HCMV replication has been demonstrated, relatively little is known about the activity of cellular phosphatases. We conducted a series of experiments designed to investigate the effect of HCMV infection on cellular serine/threonine phosphatase activity. We found that the abundance of two major cellular serine/threonine phosphatases, PP1 and PP2A,...
While cytomegalovirus (CMV) infects and replicates in a multitude of cell types, the ability of the virus to replicate in antigen presenting cells (APCs) is believed to play a critical role in the viral dissemination and latency. CMV infection of APCs and manipulation of their function are important areas of investigation. CMV down regulation of MHC II is reportedly mediated by the HCMV proteins US2,...
We reported previously that the guinea pig cytomegalovirus (CMV) stock purchased from the American Type Culture Collection contained two types of strains, one containing and the other lacking a 1.6 kb locus, and that the 1.6 kb locus was required for efficient viral growth in animals but not in cell culture. In this study, we characterized the genetic contents of the locus, and found that i) the 1...
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