title: Mouse serum factor(s) down-modulate the CD4 and CXCR4 molecules on human T cells conferring resistance to HIV infection in NOG mice.
abstract: Human cells have developed innate immunity, exploiting several means to block virus infection, and viruses have evolved diverse strategies to resist these. We show here that the human immunodeficiency virus 1 (HIV-1) could neither progressively infect engrafted human leukemic T cells nor repress their growth in NOG mice. However, ED-40515(-) cells infected with HIV-1 before inoculation were found to significantly delay the onset of tumor growth and increased the survival period of NOG mice. ED-40515(-) tumor cells showed resistance to HIV-1 which was apparently correlated with the down-regulation of CD4 and CXCR4 molecules in NOG mice. Serum from three different mouse strains, including NOG, retained a suppressive effect on the CD4 molecule of ED-40515(-) cells in vitro. ED-40515(-) cells obtained from mice re-expressed CD4 and CXCR4 molecules upon in vitro culture and were again successfully infected with HIV-1. These findings indicate that HIV-1 may initially successfully delay or regress tumor growth in NOG mice, but eventually fails to do so because of the evolution of HIV-resistant cells due to a rapid down-modulation of CD4 and CXCR4. Our data also demonstrated that some unknown soluble factor(s) present in mouse serum was responsible for conferring resistance to HIV infection to human T cells.
authors.affiliation: Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8519, Japan.
authors.forename: Md Zahidunnabi
authors.initials: MZ
authors.lastname: Dewan
authors.forename: Kazuo
authors.initials: K
authors.lastname: Terashima
authors.forename: Sunjida
authors.initials: S
authors.lastname: Ahmed
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohba
authors.forename: Midori
authors.initials: M
authors.lastname: Taruishi
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D015704:CD4 Antigens / Q000378:metabolism*; D002352:Carrier Proteins; D002461:Cell Line, Transformed / Q000276:immunology / Q000821:virology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019718:Receptors, CXCR4 / Q000378:metabolism*; D044967:Serum / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000099176:Noggin Protein
chemical_list: D001685:Biological Factors; D015704:CD4 Antigens; D002352:Carrier Proteins; D019718:Receptors, CXCR4; D000099176:Noggin Protein