Document 1009
 DOCN  M9541009
 TI    Feline immunodeficiency virus infection of macrophages: in vitro and in
       vivo inhibition by dideoxycytidine-5'-triphosphate-loaded erythrocytes.
 DT    9504
 AU    Magnani M; Rossi L; Fraternale A; Silvotti L; Quintavalla F; Piedimonte
       G; Matteucci D; Baldinotti F; Bendinelli M; Istituto di Chimica
       Biologica, Universita di Urbino, Italy.
 SO    AIDS Res Hum Retroviruses. 1994 Sep;10(9):1179-86. Unique Identifier :
       AIDSLINE MED/95127301
 AB    Although HIV-1 and other mammalian lentiviruses infect macrophages, they
       are not cytopathic. Consequently, these infected long-lived cells serve
       as major virus reservoirs with a key role in the propagation of the
       virus throughout the body as well as in the pathogenesis of AIDS.
       Furthermore, well-differentiated macrophages possess low abilities to
       phosphorylate the most common reverse transcriptase inhibitors of the
       nucleoside analog family. In an attempt to overcome these problems we
       have evaluated in vitro and in vivo in a feline immunodeficiency animal
       model whether it is possible to protect macrophages from FIV infection
       by direct administration of dideoxycytidine-5'-triphosphate (ddCTP).
       Because the cell membranes are impermeable to phosphorylated drugs we
       have encapsulated ddCTP into autologous erythrocytes. The drug-loaded
       erythrocyte membranes were then modified to target these carrier cells
       to macrophages. ddCTP-loaded erythrocytes were able to reduce FIV
       production by macrophages infected in vitro or obtained from naturally
       or experimentally infected cats. Furthermore, the administration of
       ddCTP-loaded erythrocytes protected the majority of peritoneal
       macrophages during a 7-month experimental FIV infection and reduced the
       percentage of circulating lymphocytes stained by an anti-p24 antibody.
       These results suggest that the administration of nucleoside analogs in
       phosphorylate form is feasible and their targeting to macrophages
       reduces FIV infection both in vitro and in vivo.
 DE    Animal  Antiviral Agents/ADMINISTRATION & DOSAGE/PHARMACOLOGY  Cats
       Cells, Cultured  Deoxycytosine Nucleotides/*ADMINISTRATION &
       DOSAGE/*PHARMACOLOGY/  THERAPEUTIC USE  Drug Carriers  *Erythrocytes
       Feline Acquired Immunodeficiency Syndrome/BLOOD/*DRUG THERAPY/
       IMMUNOLOGY  Immunodeficiency Virus, Feline/DRUG EFFECTS/*PHYSIOLOGY
       Lymphocytes/VIROLOGY  Macrophages/*VIROLOGY  Monocytes/VIROLOGY
       Support, Non-U.S. Gov't  Virus Replication/*DRUG EFFECTS  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).