Mouse serum factor(s) down-modulate the CD4 and CXCR4 molecules on human T cells conferring resistance to HIV infection in NOG mice.
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.
Dewan
Md Zahidunnabi
MZ
Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8519, Japan.
Terashima
Kazuo
K
Ahmed
Sunjida
S
Ohba
Kenji
K
Taruishi
Midori
M
Yamamoto
Naoki
N
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
D001685:Biological Factors; D015704:CD4 Antigens; D002352:Carrier Proteins; D019718:Receptors, CXCR4; D000099176:Noggin Protein