TNF-alpha, produced by feline infectious peritonitis virus (FIPV)-infected macrophages, upregulates expression of type II FIPV receptor feline aminopeptidase N in feline macrophages.
The pathogenicity of feline infectious peritonitis virus (FIPV) is known to depend on macrophage tropism, and this macrophage infection is enhanced by mediation via anti-S antibody (antibody-dependent enhancement, ADE). In this study, we found that TNF-alpha production was increased with viral replication in macrophages inoculated with a mixture of FIPV and anti-S antibody, and demonstrated that this culture supernatant had feline PBMC apoptosis-inducing activity. We also demonstrated that the expression level of the FIPV virus receptor, feline aminopeptidase N (fAPN), was increased in macrophages of FIP cats. For upregulation of TNF-alpha and fAPN in macrophages, viral replication in macrophages is necessary, and their expressions were increased by ADE of FIPV infection. It was demonstrated that a heat-resistant fAPN-inducing factor was present in the culture supernatant of FIPV-infected macrophages, and this factor was TNF-alpha: fAPN expression was upregulated in recombinant feline TNF-alpha-treated macrophages, and FIPV infectivity was increased in these macrophages. These findings suggested that FIPV replication in macrophages increases TNF-alpha production in macrophages, and the produced TNF-alpha acts and upregulates fAPN expression, increasing FIPV sensitivity.
Takano
Tomomi
T
Department of Veterinary Infectious Disease, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori 034-8628, Japan.
Hohdatsu
Tsutomu
T
Toda
Ayako
A
Tanabe
Maki
M
Koyama
Hiroyuki
H
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D018826:CD13 Antigens / Q000378:metabolism*; D002415:Cats; D002478:Cells, Cultured; D016765:Coronavirus, Feline / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D017077:Culture Media, Conditioned; D017931:DNA Primers / Q000235:genetics; D016766:Feline Infectious Peritonitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects
D017077:Culture Media, Conditioned; D017931:DNA Primers; D012333:RNA, Messenger; D012367:RNA, Viral; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018826:CD13 Antigens