Differential patterns of human cytomegalovirus gene expression in various T‐cell lines carrying human T‐cell leukemia‐lymphoma virus type I: Role of tax‐activated cellular transcription factors

Beck, Zoltán; Bácsi, Attila; Liu, Xiangdong; Ebbesen, Peter; Andirkó, István; Csoma, Eszter; Kónya, József; Nagy, Etelka; Tóth, Ferenc

doi:10.1002/jmv.10447

Cited by 4 publications

(2 citation statements)

References 37 publications

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“…Cell-typedependent effects of Tax on cellular transcription factors have been known for years. While Tax had a positive effect on NF-B activity but no effect or a slightly negative effect on Sp1 activity in HL-60 cells in this study, Sp1 activity was reported to be variable among HTLV-1 Tax-positive cell lines (3).…”

Section: Discussioncontrasting

confidence: 61%

Induction of Lactoferrin Gene Expression in Myeloid or Mammary Gland Cells by Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax: Implications for Milk-Borne Transmission of HTLV-1

Moriuchi

2006

J Virol

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Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma and is transmitted vertically via breast milk and horizontally via semen in areas of endemicity (reviewed in references 11 and 45). Breast milk contains a number of cells (e.g., neutrophils, macrophages, and lymphocytes), as well as a wide variety of bioactive factors, that exert antimicrobial activity (reviewed in reference 9). Lactoferrin is a major milk protein that acts as a nonspecific antimicrobial agent against pathogenic bacteria, fungi, and other viruses (including human immunodeficiency virus [HIV], herpes simplex virus, cytomegalovirus, and rotavirus) (reviewed in reference 43). A major source of lactoferrin in breast milk has not been determined; however, neutrophils have been shown to be major producers of lactoferrin (18) and to exist in large quantities in breast milk (9). Mucosal epithelial cells are also thought to be a source of lactoferrin in body fluids, including breast milk. Lactoferrin is also released from neutrophils in inflammatory sites, where lymphocytes, the major target of HTLV-1, are recruited (18). We have previously demonstrated that lactoferrin enhances HTLV-1 replication and transmission, at least in part, by upregulating the HTLV-1 long terminal repeat (LTR) promoter (29). Although lactoferrin exerts its antiviral activity by inhibiting viral entry into cells, lactoferrin appears to have little effect on cell-to-cell spread of HTLV-1, a highly cell-associated virus. Such a "smart" strategy, which utilizes a host antimicrobial factor for its replication and transmission, might have been established through a long period of coevolution between humans and HTLV-1.In the present study, we show that HTLV-1 infection can induce expression of lactoferrin. While mammary epithelial cells have previously been shown to support and transfer productive HTLV-1 infection in vitro (19), HTLV-1 is not able to efficiently replicate in myeloid cells. However, HTLV-1 infection could induce expression of lactoferrin mRNA in those cells in a paracrine manner, where a soluble form of the Tax transactivator appears to play a role. Tax has been shown to be released from infected cells and to exert biological activity in neighboring uninfected cells (1, 5, 6, 20-23, 26, 38). Tax transactivates the lactoferrin gene promoter in both myeloid and mammary epithelial cells. Therefore, it is possible that Tax released from HTLV-1-infected T cells contributes to lactoferrin production by stimulating neighboring cells. Such mutual interaction between HTLV-1 and lactoferrin has implications for milk-borne transmission of HTLV-1. MATERIALS AND METHODSCells. HL-60 cells were grown in RPMI 1640 medium with 10% fetal bovine serum and induced for differentiation to the metamyelocyte stage or beyond by adding dimethyl sulfoxide (DMSO) to 1.25% for 5 days until Ͼ90% of the cells reduced nitroblue tetrazolium dye (data not shown). MCF-7 cells were grown in RPMI 1640 with 10% fetal bovine serum. HTLV-1-infected MT-2 cells ...

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Section: Discussioncontrasting

confidence: 61%

Induction of Lactoferrin Gene Expression in Myeloid or Mammary Gland Cells by Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax: Implications for Milk-Borne Transmission of HTLV-1

Moriuchi

2006

J Virol

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“…Huh-7 cells were incubated with 20 μg/ml of DHMEQ for 1-24 h. The nuclear extract was prepared as described previously (22). As a positive control, the nuclear extract from HUT-78 cells containing NF-κB (23) . Immunofluorescence for rhodamine was analyzed by Olympus BX50 microscope (Tokyo, Japan) and images were digitally captured using a Nikon DXM 1200 digital camera (Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

DHMEQ, a novel NF-kB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells

Nishimura

Ishikawa²,

Matsumoto³

et al. 2006

Int J Oncol

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Several reports have indicated that nuclear factor-κB (NF-κB) is constitutively activated in a variety of cancer cells including hepatoma cells and plays a key role in their growth and survival. Dehydroxymethylepoxyquinomicin (DHMEQ) derived from the structure of an antibiotic epoxyquinomicin C is a novel NF-κB inhibitor. In the present study, we evaluated the effect of DHMEQ on the NF-κB activity in human hepatoma cells, Huh-7, HepG2 and Hep3B, and the anti-tumor effect of DHMEQ on these cells in vitro and in vivo. DHMEQ inhibited the steady-state transcriptional activity of NF-κB in all hepatoma cells. DHMEQ blocked the constitutive DNAbinding activity and TNF-•-mediated nuclear translocation of NF-κB in Huh-7 cells. DHMEQ (5-20 μg/ml) dose-dependently reduced the viable cell number of all hepatoma cells. DHMEQ (20 μg/ml) induced apoptosis in all hepatoma cells, especially in Hep3B cells, and cell-cycle arrest in Huh-7 and HepG2 cells. These effects were accompanied by downregulation of proteins involved in anti-apoptosis (Bcl-xL, XIAP or c-IAP2) and cell-cycle progression (cyclin D1), and induction of proteins involved in pro-apoptosis (Bax) and cell-cycle retardation (p21 Waf1/Cip1), although the degree of changes by DHMEQ was different in each hepatoma cell type. Moreover, intraperitoneal administration of DHMEQ (8 mg/kg) significantly repressed the growth of Huh-7 tumor subcutaneously transplanted into BALB/c nu/nu athymic mice. Our results suggest that DHMEQ could qualify as a candidate for a new chemotherapeutic agent against human hepatoma.

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Effects of Random Mutations in the Human Immunodeficiency Virus Type 1 Transcriptional Promoter on Viral Fitness in Different Host Cell Environments

Opijnen

Boerlijst

Berkhout

2006

J Virol

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A mutation's effect on fitness or phenotype may in part depend on the interaction of the mutation with the environment. The resulting phenotype or fitness is important, since it determines the adaptive potential of a species. To date, most studies have focused on alterations to protein-coding regions of the genome and their consequential fitness effects. Non-protein-coding regulatory regions have been largely neglected, although they make up a large and important part of an organism's genome. Here, we use human immunodeficiency virus type 1 as a model system to investigate fitness effects of random mutations in noncoding DNA-binding sites of the transcriptional promoter. We determined 242 fitness values for 35 viral promoter mutants with one, two, or three mutations across seven distinct cellular environments and identified that (i) all mutants have an effect in at least one cellular environment; (ii) fitness effects are highly dependent on the cellular environment; (iii) disadvantageous and advantageous mutations occur at high and similar frequencies; and (iv) epistatic effects of multiple mutations are rare. Our results underline the evolutionary potential of regulatory regions and indicate that DNA-binding sites evolve under strong selection, while at the same time, they are very plastic to environmental change.

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Differential patterns of human cytomegalovirus gene expression in various T‐cell lines carrying human T‐cell leukemia‐lymphoma virus type I: Role of tax‐activated cellular transcription factors

Cited by 4 publications

References 37 publications

Induction of Lactoferrin Gene Expression in Myeloid or Mammary Gland Cells by Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax: Implications for Milk-Borne Transmission of HTLV-1

Induction of Lactoferrin Gene Expression in Myeloid or Mammary Gland Cells by Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax: Implications for Milk-Borne Transmission of HTLV-1

DHMEQ, a novel NF-kB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells

Effects of Random Mutations in the Human Immunodeficiency Virus Type 1 Transcriptional Promoter on Viral Fitness in Different Host Cell Environments

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