We describe the identification, experimental transmission, and pathogenesis of a naturally occurring powerfully immunosuppressive isolate of feline leukemia virus (designated here as FeLV-
FAIDS) which induces fatal
acquired immunodeficiency syndrome (
AIDS) in 100% (25 of 25) of persistently viremic experimentally infected specific pathogen-free (SPF) cats after predictable survival periods ranging from less than 3 months (acute immunodeficiency syndrome) to greater than one year (chronic immunodeficiency syndrome), depending on the age of the cat at time of virus exposure. The pathogenesis of FeLV-
FAIDS-induced feline immunodeficiency disease is characterized by: a
prodromal period of largely asymptomatic
viremia; progressive
weight loss, lymphoid
hyperplasia associated with viral replication in lymphoid follicles, lymphoid depletion associated with extinction of viral replication in lymphoid follicles, intractable
diarrhea associated with
necrosis of intestinal crypt epithelium,
lymphopenia, suppressed lymphocyte blastogenesis, impaired cutaneous allograft rejection,
hypogammaglobulinemia, and
opportunistic infections such as bacterial respiratory disease and necrotizing
stomatitis. The clinical onset of immunodeficiency syndrome correlates with the replication of a specific FeLV-
FAIDS viral variant, detected principally as unintegrated
viral DNA, in bone marrow, lymphoid tissues, and intestine. Two of seven cats with chronic immunodeficiency disease that survived greater than 1 year after inoculation developed
lymphoma affecting the marrow, intestine, spleen, and mesenteric nodes. Experimentally induced feline immunodeficiency syndrome, therefore, is a rapid and consistent in vivo model for prospective studies of the viral genetic determinants, pathogenesis, prevention, and
therapy of retrovirus-induced immunodeficiency disease.