title: Protocatechuic acid, a novel active substance against avian influenza virus H9N2 infection.
abstract: Influenza virus H9N2 subtype has triggered co-infection with other infectious agents, resulting in huge economical losses in the poultry industry. Our current study aims to evaluate the antiviral activity of protocatechuic acid (PCA) against a virulent H9N2 strain in a mouse model. 120 BALB/c mice were divided into one control group, one untreated group, one 50 mg/kg amantadine hydrochloride-treated group and three PCA groups treated 12 hours post-inoculation with 40, 20 or 10 mg/kg PCA for 7 days. All the infected animals were inoculated intranasally with 0.2 ml of a A/Chicken/Hebei/4/2008(H9N2) inoculum. A significant body weight loss was found in the 20 mg/kg and 40 mg/kg PCA-treated and amantadine groups as compared to the control group. The 14 day survivals were 94.4%, 100% and 95% in the PCA-treated groups and 94.4% in the amantadine hydrochloride group, compared to less than 60% in the untreated group. Virus loads were less in the PCA-treated groups compared to the amantadine-treated or the untreated groups. Neutrophil cells in BALF were significantly decreased while IFN-γ, IL-2, TNF-α and IL-6 decreased significantly at days 7 in the PCA-treated groups compared to the untreated group. Furthermore, a significantly decreased CD4+/CD8+ ratio and an increased proportion of CD19 cells were observed in the PCA-treated groups and amantadine-treated group compared to the untreated group. Mice administered with PCA exhibited a higher survival rate and greater viral clearance associated with an inhibition of inflammatory cytokines and activation of CD8+ T cell subsets. PCA is a promising novel agent against bird flu infection in the poultry industry.
authors.affiliation: College of Animal Science, Henan Institute of Science and Technology, Xinxiang, China; Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Changbo
authors.initials: C
authors.lastname: Ou
authors.affiliation: College of Life Sciences, Agricultural University of Hebei, Baoding, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Shi
authors.affiliation: Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Qunhui
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Zongxue
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, and Yerkes Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Baozhong
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, and Yerkes Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.affiliation: Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: He
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016516:CD4-CD8 Ratio; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D062385:Hydroxybenzoates / Q000008:administration & dosage / Q000494:pharmacology*; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects*; D018655:Lymphocyte Count; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000821:virology*; D011024:Pneumonia, Viral / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000821:virology; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D062385:Hydroxybenzoates; C009091:protocatechuic acid