title: Inhibition of African swine fever virus in cultured swine monocytes by phosphonoacetic acid (PAA) and by phosphonoformic acid (PFA).
abstract: The use of phosphonoacetic (PAA) and phosphonoformic acid (PFA) as inhibitors of African swine fever virus (ASFV) replication in porcine monocytes/macrophages (MO) was investigated. At concentrations sufficient to inhibit replication, hemadsorption, and cytopathogenic damage by high inocula of ASFV, both antiviral agents were cytostatic and suppressed the DNA-synthetic growth response of porcine MO to the MO-specific colony-stimulating factor-1 (CSF-1). PAA and PFA inhibited ASFV-associated DNA-synthesis in the cytoplasm of infected swine MO. Using ASFV-specific monoclonal antibodies in immunebinding assays and in immunoprecipitation analysis of radiolabeled proteins of infected MO, PAA and PFA inhibited the synthesis of ASFV proteins of 13, 73, and 150/220 kDa, and caused a variable inhibition in the synthesis of a 12 kDa ASFV protein. These antiviral drugs, however, did not prevent the appearance of an early 32 kDa ASFV protein. The cytostatic and virus-suppressive effects of PAA and PFA could be reversed. ASFV resumed growth in infected MO cultures, if the cells maintained in medium with CSF-1 were removed from the antivirals before 1 week of drug exposure. With prolonged exposure to PAA or PFA (beyond 1 week), ASFV could not be recovered from infected MO cultures.
authors: Plum Island Animal Disease Center, USDA-ARS, Greenport, New York.
authors: F
authors: F
authors: Villinger
authors: E V
authors: EV
authors: Genovesi
authors: D J
authors: DJ
authors: Gerstner
authors: T C
authors: TC
authors: Whyard
authors: R C
authors: RC
authors: Knudsen
mesh_terms: D000358:African Swine Fever Virus / Q000187:drug effects* / Q000254:growth & development; D000818:Animals; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral / Q000096:biosynthesis; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002458:Cell Fractionation; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D017245:Foscarnet; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D009000:Monocytes; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011233:Precipitin Tests; D011863:Radioimmunoassay; D013552:Swine; D014776:Virus Cultivation; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000998:Antiviral Agents; D017245:Foscarnet; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D010746:Phosphonoacetic Acid