Inhibition of African swine fever virus in cultured swine monocytes by phosphonoacetic acid (PAA) and by phosphonoformic acid (PFA).
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.
Villinger
F
F
Plum Island Animal Disease Center, USDA-ARS, Greenport, New York.
Genovesi
E V
EV
Gerstner
D J
DJ
Whyard
T C
TC
Knudsen
R C
RC
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
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000998:Antiviral Agents; D017245:Foscarnet; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D010746:Phosphonoacetic Acid