Differential lung NK cell responses in avian influenza virus infected chickens correlate with pathogenicity.
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ABSTRACT:
SUBMITTER: Jansen CA
PROVIDER: S-EPMC3748423 | biostudies-other | 2013
REPOSITORIES: biostudies-other
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Project description:Since April 2014, new infections of H5N6 avian influenza virus (AIV) in humans and domestic poultry have caused considerable economic losses in the poultry industry and posed an enormous threat to human health worldwide. In previous research using gene sequence and phylogenetic analysis, we reported that H5N6 AIV isolated in February 2015 (ZH283) in Pallas's sandgrouse was highly similar to that isolated in a human in December 2015 (A/Guangdong/ZQ874/2015), whereas a virus (i.e., SW8) isolated in oriental magpie-robin in 2014 was highly similar to that of A/chicken/Dongguan/2690/2013 (H5N6). However, the pathogenicity, transmissibility, and host immune-related response of chickens infected by those wild bird-origin H5N6 AIVs remain unknown. In response, we examined the viral distribution and mRNA expression profiles of immune-related genes in chickens infected with both viruses. Results showed that the H5N6 AIVs were highly pathogenic to chickens and caused not only systemic infection in multiple tissues, but also 100% mortality within 3-5 days post-infection. Additionally, ZH283 efficiently replicated in all tested tissues and transmitted among chickens more rapidly than SW8. Moreover, quantitative real-time polymerase chain reaction analysis showed that following infection with H5N6, AIVs immune-related genes remained active in a tissue-dependent manner, as well as that ZH283 induced mRNA expression profiles such as TLR3, TLR7, IL-6, TNF-α, IL-1β, IL-10, IL-8, and MHC-II to a greater extent than SW8 in the tested tissues of infected chickens. Altogether, our findings help to illuminate the pathogenesis and immunologic mechanisms of H5N6 AIVs in chickens.
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Project description:We analyzed five H5N1 avian influenza viruses (AIVs) isolated from different birds in 2012 in China. Based on whole-genome sequences, we divided the viruses into four genotypes. The DKE26, GSE43, and DKE53 viruses belonged to Genotypes 1-3, respectively. The CKE93 and CKE96 viruses were classified into Genotype 4. Genotypes 1-3 correspond to the viruses containing the HA gene of clade 2.3.2, and Genotype 4 is the virus that bears the HA gene of clade 7.2. To better understand the pathogenicity and transmission of the viruses, we infected chickens with 103 EID50/0.1 ml GSE43 (clade 2.3.2) or CKE93 (clade 7.2) virus. Our results revealed that 6 of 7 specific-pathogen-free (SPF) chickens inoculated with GSE43 virus were dead before 7-day post-infection, but all the SPF chickens inoculated with CKE93 virus survived the infection. Both the GSE43 and CKE93 viruses replicated systemically in chickens. The virus titers of GSE43 virus in tested organs were obviously higher than those of CKE93 virus. Our results revealed that the pathogenicity and replication of GSE43 in chickens was much higher than those of CKE93. The GSE43 virus could transmit between chickens, but the CKE93 could not transmit between chickens by naïve contact. Therefore, different clades of H5N1 AIVs possessed variable pathogenicities and transmission abilities among chickens. Our study contributes to knowledge of pathogenic variations of prevalent H5N1 viruses.
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Project description:The H9N2 strains of avian influenza viruses (AIVs) circulate worldwide in poultry and cause sporadic infection in humans. To better understand the evolution of these viruses while circulating in poultry, an H9N2 chicken isolate was passaged 19 times in chickens via aerosol inoculation. Whole-genome sequencing showed that the viruses from the initial stock and those after the 8th and 19th passages (P0, P8, and P19) all had the same monobasic cleavage site in the hemagglutinin (HA), typical for viruses of low pathogenicity. However, at position 226 of the HA protein the ratio of glutamine (which favors avian-type receptor binding) to leucine (which favors mammalian-type receptor binding) decreased from 54:46 in P0, to 87:13 in P8, and then 0:100 in P19. In chickens exposed to aerosols of P0, P8, or P19, replication of the viruses was similar and mainly limited to the respiratory tract. None of the infected chickens showed any clinical signs. Over the 19 passages the viruses maintained relatively stable infectivity but gradually lost lethality to chicken embryos. According to the hemagglutination inactivation assay, P8 was slightly and P19 significantly (P < 0.05) less thermostable than P0. Collectively, after 19 passages in chickens the H9N2 AIVs retained low pathogenicity with a positive selection of L226 in the HA. These findings suggest that H9N2 viruses might acquire mammalian specificity after asymptomatic circulation in avian species.
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Project description:Highly pathogenic avian influenza H5N6 viruses have been circulating in poultry in Asia since 2013 and producing serious diseases in chickens. Here, we analyzed the genetic properties of 10 H5N6 subtypes AIVs from geese in 2015-2016 in Guangdong province. Phylogenic analysis showed that all HA genes of the 10 viruses belonged to clade 2.3.4.4, and their genes including HA, PA, PB1, M, NP, and NS all derived from Mix-like 1 (CH, VN, LS). Their PB2 genes come from Mix-like 2 (CH, VN, JP). The NA genes were classified into a Eurasian lineage. Therefore, the 10 viruses likely originate from the same ancestor and were all recombinant viruses between different genotypes. We selected A/Goose/Guangdong/GS144/2015(H5N6) (GS144) and A/Goose/Guangdong/GS148/2016(H5N6) (GS148) viruses to inoculate 5-week-old chickens intranasally with 104 EID50/0.1 mL dose intranasally to assess their pathogenicity and transmissibility. Inoculated chickens showed that the GS144 virus caused systematic infection with a lethality of 100%, but the lethality of GS148 virus was 0%. The two viruses were efficiently transmitted to contact chickens. The lethality of GS144 and GS148 virus in contact with chickens was 87.5% and 0%, respectively, which suggests that the transmissibility of GS144 virus was stronger than GS148 virus in chickens. Thus, different H5N6 viruses from the same waterfowl can show different pathogenicity and transmissibility in chickens. Continued surveillance and characteristic analysis of the H5N6 viruses will help us to keep abreast of evolution and variation in avian influenza viruses in the future.
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