Relationship between HOX2 homeobox gene expression and the human cytomegalovirus immediate early genes

Kadota, Chika; Nagahama, Masato; Tsutsui, Yoshihiro

doi:10.1099/0022-1317-73-4-975

Cited by 6 publications

(6 citation statements)

References 27 publications

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“…In these studies, since MCMV was injected into the uteri, it is possible that the embryos might have been infected with MCMV after a certain period of development through the infected maternal uteri, or that the abnormalities might have been induced by M C M V without viral gene expression. In this regard, we reported that H C M V activated HOX2E homeobox gene without expression of the immediate early genes [18]. It has been reported that an undifferentiated human embryonat carcinoma (EC) cell line was not permissive for H C M V replication, but that some of the cells became permissive when they were induced to differentiate with retinoic acid [8,9].…”

Section: Discussionmentioning

confidence: 96%

Susceptibility of mouse embryo to murine cytomegalovirus infection in early and mid-gestation stages

Kashiwai

Kawamura

Kadota

et al. 1992

Archives of Virology

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The susceptibility of mouse embryonic cells to murine cytomegalovirus (MCMV) infection was studied by injecting the virus in the early and mid-gestation stages. For the early stage, blastocysts from BDF1 mice were injected with MCMV or minimal essential medium (MEM) by micromanipulator and returned to the uteri of pseudopregnant ICR mice. On day 11 of gestation, the embryos were examined immunohistochemically, using antibody specific to the early antigen of MCMV, and the placentae were examined by plaque assay. No infection was detected by either method. Furthermore, no infection was detected in MCMV-infected blastocysts that were cultured and examined for infection by immunofluorescence. For mid-gestation embryos, the conceptus was injected with MCMV on day 8.5 of gestation and was subjected to immunohistochemical analysis from day 10.5 to 12.5 of gestation. Viral antigen-positive cells were first observed in the placentae, then antigen-positive cells appeared among the blood cells, endothelial and mesodermal cells of the embryos. On day 12.5 of gestation, clusters of viral antigen-positive cells were sometimes observed in the hearts and livers. Although the incidence was lower, viral antigen-positive cells were also observed in the neuroectoderm and the eyes. These results suggest that MCMV does not infect early embryos and that infection first occurs in the placenta of postimplantation embryos, whence it extends through the blood cells to the endothelial and mesodermal cells of different embryonic regions, eventually extending to the neuroectoderm.

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Section: Discussionmentioning

confidence: 96%

Susceptibility of mouse embryo to murine cytomegalovirus infection in early and mid-gestation stages

Kashiwai

Kawamura

Kadota

et al. 1992

Archives of Virology

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“…Indeed, Hox proteins have been described to influence gene expression and viral replication of two DNA viruses. Recently, Kadota and colleagues identified a functional correlation between human cytomegalovirus (HCMV) immediate-early gene transcription and HoxB5 expression (35), and herpes simplex virus 1 (HSV-1) replicates more efficiently in the corneas of transgenic mice with enhanced HoxA5 expression (24,48).…”

Section: Discussionmentioning

confidence: 99%

“…One of the potential interaction partners found in the yeast two-hybrid screen encoded a partial cDNA for HoxB7 (nt 372 to 1170), a protein belonging to the homeobox protein family of transcription factors (61). To further investigate this interaction, bacterially expressed and purified GST-E4orf6 was incubated with in vitro-translated, 35 S-labeled HoxB7. Only GST-E4orf6, not GST alone, bound to HoxB7, while no interaction was observed between GST-E4orf6 and an in vitro-translated control protein, confirming a direct interaction between HAdV5 E4orf6 and the cellular homeobox protein HoxB7 (Fig.…”

Section: Cellular Homeobox Transcription Factor Hoxb7 Is a Novelmentioning

confidence: 99%

“…After centrifugation (10 min, 4°C, 10,000 rpm), 1.5 ml of 10% Triton X-100 was added to the clarified supernatant, sterile filtered (pore size of 0.45 m), and incubated for 1 h with glutathione Sepharose 4B (GE Healthcare) on a rotator at 4°C. The Sepharose beads were washed six times with Tris-buffered saline (TBS) with protease inhibitors, and similar amounts of GST or GST fusion protein, as determined by SDS-PAGE followed by Coomassie blue staining, were incubated overnight at 4°C with reticulocyte lysate containing in vitro-translated 35 S-labeled target proteins. Proteins were translated using a TNT coupled reticulocyte lysate system as described by the manufacturer (Promega).…”

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confidence: 99%

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Functional Cooperation between Human Adenovirus Type 5 Early Region 4, Open Reading Frame 6 Protein, and Cellular Homeobox Protein HoxB7

Müller

Schreiner

Schmid

et al. 2012

J Virol

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cHuman adenovirus type 5 (HAdV5) E4orf6 (early region 4 open reading frame 6 protein) is a multifunctional early viral protein promoting efficient replication and progeny production. E4orf6 complexes with E1B-55K to assemble cellular proteins into a functional E3 ubiquitin ligase complex that not only mediates proteasomal degradation of host cell substrates but also facilitates export of viral late mRNA to promote efficient viral protein expression and host cell shutoff. Recent findings defined the role of E4orf6 in RNA splicing independent of E1B-55K binding. To reveal further functions of the early viral protein in infected cells, we used a yeast two-hybrid system and identified the homeobox transcription factor HoxB7 as a novel E4orf6-associated protein.Using a HoxB7 knockdown cell line, we observed a positive role of HoxB7 in adenoviral replication. Our experiments demonstrate that the absence of HoxB7 leads to inefficient viral progeny production, as HAdV5 gene expression is highly regulated by HoxB7-mediated activation of various adenoviral promoters. We have thus identified a novel role of E4orf6 in HAdV5 gene transcription via regulation of homeobox protein-dependent modulation of viral promoter activity. Human adenovirus type 5 (HAdV5) E4orf6 (early region 4 open reading frame 6 protein) is a multifunctional protein which promotes efficient viral replication and plays a major role in adenoviral transformation processes. During infection, this viral factor assembles an SCF-like E3 ubiquitin ligase complex based on the cellular proteins elongins B and C, cullin 5, and Rbx1 (4, 66; reviewed in references 74 and 83). In cooperation with E1B-55K (early region 1B 55K protein), this viral RING-type ligase ubiquitinates cellular substrates prior to proteasomal degradation. So far, p53, DNA ligase IV, Mre11, integrin ␣3, and BLM (Blooms helicase) have been identified as targets of this HAdV5 ligase complex (4,18,64,83).E1B-55K was also identified as a viral interaction partner of the transcription factor Daxx (76,79,89) and is required for proteasomal degradation of Daxx during HAdV5 infection (75, 76). Remarkably, in contrast to the cellular targets of HAdV5 E3 ubiquitin ligases mentioned above, E4orf6 is dispensable for Daxx removal. In reverse, the HAdV12 E4orf6 protein was shown to target TopBP1, a protein involved in the DNA damage response and cell cycle checkpoint control (70, 71). In this case, HAdV12 E1B-55K is apparently not relevant for the cullin2-E4orf6-dependent proteasomal degradation of TopBP1 (5). In addition, it was shown that formation of the HAdV5 E3 ubiquitin ligase complex is necessary for E4orf6-and E1B-55K-mediated export of viral late mRNA out of the nucleus into the cytoplasm (7, 88). This preferential export of viral transcripts over cellular mRNA is important for efficient viral protein expression and host cell shutoff.However, different studies show that during the course of infection, only up to 50% of E4orf6 is associated with E1B-55K (16,60,80). Therefore, we were interested in ad...

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“…HOXA7 can also stimulate breast cancer cell proliferation by increasing the estrogen receptor alpha (Zhang et al, 2013). In addition, HCMV infection or early antigen of HCMV can induce a variety of abnormal expression of HOX genes (Kadota et al, 1992). According to the information mentioned above, the present study was designed to know whether HOX genes play a role in the occurrence of vascular diseases induced by HCMV.…”

Section: Introductionmentioning

confidence: 99%

HHEX: A Crosstalker between HCMV Infection and Proliferation of VSMCs

Liu

Kang

et al. 2016

Front. Cell. Infect. Microbiol.

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Objective: The study was designed to evaluate the role of Human cytomegalovirus (HCMV) infection on homebox (HOX) gene expression and the effects of overexpression of HOX genes on proliferation and apoptosis of vascular smooth muscle cells (VSMCs).Methods: Viral infection was verified by observation of cytopathic effects through inverted microscopy, viral particles by electron microscopy and HCMV IE gene amplification by RT-PCR. cDNA profiling technology was used to screen expression of HOX genes after HCMV infection in VSMCs. Abnormal expression of Haematopoietically-expressed homeobox (HHEX) was selected to construct over-expressed vector and transfected into VSMCs. The effects of over expression of HHEX on cell proliferation and apoptosis of VSMCs were assayed by flow cytometry. Apoptosis and proliferation-associated genes were also assayed by RT-PCR.Results: Multiple HOX gene expression levels had obvious changes after HCMV infection, among which expression of HHEX gene increased obviously at 24, 48, and 72 h after infection. Over expression of HHEX can promote VSMCs proliferation by promoting G0/G1 phase cells into S phase and inhibit VSMCs apoptosis. HHEX inhibited the expression of apoptosis-associated caspase 2 and caspase3 and promoted the expression of cell cycle-related genes such as CDK2 and CDK6, CyclinB2 and CyclinD2.Conclusion: HHEX over expression induced by HCMV infection closely associated with vascular proliferative diseases.

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Relationship between HOX2 homeobox gene expression and the human cytomegalovirus immediate early genes

Cited by 6 publications

References 27 publications

Susceptibility of mouse embryo to murine cytomegalovirus infection in early and mid-gestation stages

Susceptibility of mouse embryo to murine cytomegalovirus infection in early and mid-gestation stages

Functional Cooperation between Human Adenovirus Type 5 Early Region 4, Open Reading Frame 6 Protein, and Cellular Homeobox Protein HoxB7

HHEX: A Crosstalker between HCMV Infection and Proliferation of VSMCs

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