Lack of susceptibility of cells from patients with Fabry disease to productive infection with R5 human immunodeficiency virus.
A lack of viral replication after HIV-1Ba-L (R5) but not HIV-1IIIB (X4) infection was found using in-vitro activated peripheral blood-derived mononuclear cells from patients with Fabry disease, who have a defect in the catabolism of globotriaosylceramide. CCR5, but not CD4 or CXCR4 expression levels, were lower and the surface expression of globotriaosylceramide was negligible on activated patients' cells. Our findings suggest a novel resistance mechanism to productive infection with R5 HIV-1 that potentially involves abnormal globotriaosylceramide catabolism.
Lund
Nicole
N
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Branch
Donald R
DR
Sakac
Darinka
D
Lingwood
Clifford A
CA
Siatskas
Christopher
C
Robinson
Chevalia J
CJ
Brady
Roscoe O
RO
Medin
Jeffrey A
JA
D015704:CD4 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D000795:Fabry Disease / Q000378:metabolism / Q000821:virology*; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008213:Lymphocyte Activation / Q000502:physiology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D014281:Trihexosylceramides / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
D015704:CD4 Antigens; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014281:Trihexosylceramides; C018549:globotriaosylceramide