Early therapy of feline leukemia virus infection (FeLV-FAIDS) with 9-(2-phosphonylmethoxyethyl)adenine (PMEA).
Cats infected with molecularly cloned FeLV-FAIDS develop an immunodeficiency syndrome characterized by persistent antigenemia, decline in circulating CD4+ T lymphocytes, and impaired T-cell-dependent immune responses and opportunistic infection. We evaluated the capacity of PMEA to inhibit the replication of FeLV-FAIDS in vitro and to inhibit the progression of FeLV-FAIDS infection in vivo. We found that PMEA inhibited replication of FeLV-FAIDS by greater than or equal to 50% at concentrations of greater than or equal to 0.5 microgram/ml (1.63 microM) in feline fibroblasts and prevented T lymphocyte killing at concentrations of 3 micrograms/ml. PMEA administered to cats at dosages of greater than or equal to 6.25 mg/kg/day from 0 to 49 days after FeLV-FAIDS infection prevented the development of persistent antigenemia and the induction of immunodeficiency disease. In contrast to placebo treated controls, cats successfully treated with PMEA contained viral infection, developed neutralizing antibody, and resisted a second virulent virus challenge without further therapy. Manifestations of PMEA toxicity produced by higher dosages (25 or 12.5 mg/kg/day) were anemia, leukopenia, and diarrhea. These results indicate PMEA to be a potent antiretroviral agent effective in aborting fatal progression of FeLV-FAIDS infection when therapy is initiated at the time of virus exposure.
Hoover
E A
EA
Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523.
Ebner
J P
JP
Zeidner
N S
NS
Mullins
J I
JI
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002415:Cats; D002460:Cell Line; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D005256:Leukemia Virus, Feline / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D009500:Neutralization Tests; D063065:Organophosphonates; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000998:Antiviral Agents; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine