Human T lymphocyte virus 1 from a leukemogenic cell line mediates in vivo and in vitro lymphocyte apoptosis.
HTLV-1 is implicated in the development of diverse diseases. However, most HTLV-1-infected individuals remain asymptomatic. How HTLV-1 infection leads to disparate consequences remains a mystery, despite extensive investigation of HTLV-1 isolates from infected individuals. As in human infection, experimental HTLV-1 infection in rabbits is generally benign, although HTLV-1-infected rabbit T cell lines that mediate lethal leukemia-like disease have been reported. We report here that thymuses from mature outbred rabbits inoculated with a lethal leukemia-like disease have been reported. We report here that thymuses from mature outbred rabbits inoculated with a lethal HTLV-1 T cell line (RH/K34) showed morphological and biochemical evidence of apoptosis, whereas thymuses from rabbits inoculated with nonlethal HTLV-1 T cell lines showed no signs of apoptosis. Exposure of rabbit or human lymphocytes to purified virus from RH/K34 caused rapid induction of apoptosis, providing an in vitro correlate to the pathogenic effects. By contrast, virus isolated from a nonlethal cell line mediated dose-dependent lymphocyte proliferation. These data implicate lymphocyte apoptosis as a potential mechanism by which the lethal HTLV-1 cell line causes fulminant disease and provide a means to identify factors contributing to HTLV-1 disease. Results from this HTLV-1 infection model can provide insight into variations in HTLV-1 pathogenicity in human infection.
Leno
M
M
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852, USA.
Simpson
R M
RM
Bowers
F S
FS
Kindt
T J
TJ
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology / Q000821:virology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000473:pathology / Q000821:virology*; D011817:Rabbits; D013950:Thymus Gland / Q000473:pathology* / Q000821:virology; D014407:Tumor Cells, Cultured / Q000821:virology; D014774:Virulence