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.
Human T-cell leukemia virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia, is transmitted vertically via breastfeeding. We have previously demonstrated that lactoferrin, a major milk protein, enhances HTLV-1 replication, at least in part by upregulating the HTLV-1 long terminal repeat promoter. We now report that HTLV-1 infection can induce lactoferrin gene expression. Coculture with HTLV-1-infected MT-2 cells increased the levels of lactoferrin mRNA in myeloid-differentiated HL-60 cells, as well as MCF-7 cells, models of two probable sources (neutrophils and mammary epithelium) of lactoferrin in breast milk. MT-2 cell coculture could be replaced with cell-free culture supernatants of MT-2 cells to exert the same effect. Furthermore, extracellularly administered Tax protein also induced lactoferrin gene expression at physiologically relevant concentrations. In transient-expression assays, Tax transactivated the lactoferrin gene promoter in HL-60 or MCF-7 cells. Experiments with Tax mutants, as well as site-directed mutants of the lactoferrin promoter reporters, indicated that the NF-kappaB transactivation pathway is critical for Tax induction of the lactoferrin gene promoter activity in myeloid-differentiated HL-60 cells, but not in MCF-7 cells. These results suggest that HTLV-1 infection may be able to induce expression of lactoferrin in a paracrine manner in the lactic compartment. Our findings, in conjunction with our previous study, implicate that mutual interaction between HTLV-1 and lactoferrin would benefit milk-borne transmission of this virus.
Moriuchi
Masako
M
Deparment of Molecular Microbiology and Immunology, Division of Medical Virology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Moriuchi
Hiroyuki
H
D002454:Cell Differentiation; D018920:Coculture Techniques; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016356:Gene Products, tax / Q000378:metabolism* / Q000494:pharmacology; D018922:HL-60 Cells; D015490:HTLV-I Infections / Q000378:metabolism* / Q000635:transmission; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000096:biosynthesis*; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D008895:Milk, Human / Q000821:virology; D022423:Myeloid Cells / Q000378:metabolism / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000821:virology; D019899:Paracrine Communication / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects
D016356:Gene Products, tax; D016328:NF-kappa B; D007781:Lactoferrin