Cardiac disease in transgenic mice expressing human immunodeficiency virus-1 nef in cells of the immune system.
We previously reported that a severe acquired immune deficiency syndrome-like disease develops in transgenic (Tg) mice expressing the human immunodeficiency virus-1 in its natural target cells: immature and mature CD4(+) T cells and cells of the macrophage/dendritic lineage. Here, we show that these mice also develop cardiac disease, characterized most prominently by a focal myocytolysis, occasionally by myocarditis and by deposition of endogenous immunoglobulin on cardiomyocytes. Microfil perfusion demonstrated widespread coronary arteriospasm and echocardiographic analysis revealed depressed cardiac function in Tg mice. A higher (but still modest) level of cardiomyocyte apoptosis was detected in Tg as compared to non-Tg hearts. Tg expression was detected in some of the infiltrating mononuclear cells, but not in cardiomyocytes or in cells of the heart vessels, suggesting a human immunodeficiency virus-1-induced disease process mediated by cells of the immune system. The similarity of the heart disease observed in these Tg mice to that observed in acquired immune deficiency syndrome patients suggests a common pathogenesis.
Kay
Denis G
DG
Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
Yue
Ping
P
Hanna
Zaher
Z
Jothy
Serge
S
Tremblay
Etienne
E
Jolicoeur
Paul
P
D000818:Animals; D017209:Apoptosis; D015704:CD4 Antigens / Q000235:genetics; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D015693:Gene Products, nef / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D007107:Immune System / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D015693:Gene Products, nef; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D049030:Dystroglycans