FIV infection of macrophages: in vitro and in vivo inhibition by dideoxycytidine 5'-triphosphate.
We have evaluated in vitro and in vivo whether it is possible to protect cat macrophages from feline immunodeficiency virus (FIV) infection by the administration of dideoxycytidine 5'-triphosphate (DDCTP). Since cell membranes are impermeable to phosphorylated drugs we have encapsulated DDCTP into autologous erythrocytes and modified erythrocyte membranes to target these drug-loaded cells to macrophages. DDCTP-loaded erythrocytes reduced FIV production by macrophages infected in vitro or obtained from naturally or experimentally infected cats. The same treatment protected the majority of peritoneal macrophages during a 7 month experimental FIV infection and reduced the percentage of circulating lymphocytes stained with an anti-p24 antibody. These results suggest that the administration of nucleoside analogues in phosphorylated form is feasible and their targeting to macrophages reduces FIV infection in vitro and in vivo.
Magnani
M
M
Institute of Biochemistry, University of Urbino, Italy.
Rossi
L
L
Fraternale
A
A
Silvotti
L
L
Quintavalla
F
F
Piedimonte
G
G
Matteucci
D
D
Baldinotti
F
F
Bendinelli
M
M
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D003845:Deoxycytosine Nucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D054306:Dideoxynucleotides; D004337:Drug Carriers; D004912:Erythrocytes; D016181:Feline Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects / Q000502:physiology*; D008214:Lymphocytes / Q000821:virology; D008264:Macrophages / Q000821:virology*; D017737:Macrophages, Peritoneal / Q000821:virology; D008297:Male; D013047:Specific Pathogen-Free Organisms; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D003845:Deoxycytosine Nucleotides; D054306:Dideoxynucleotides; D004337:Drug Carriers; C037406:2',3'-dideoxycytidine 5'-triphosphate