Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds

<div><p>Differences in the pathogenicity of genetically closely related H5N1 highly pathogenic avian influenza viruses (HPAIVs) were evaluated in White Leghorn chickens. These viruses varied in the clinical symptoms they induced, including lethality, virus shedding, and replication in host tissues. A comparison of the host responses in the lung, brain, and spleen suggested that the differences in viral replication efficiency were related to the host cytokine response at the early phase of infection, especially variations in the proinflammatory cytokine IL-6. Based on these findings, we inoculated the virus that showed the mildest pathogenicity among the five tested, A/pigeon/Thailand/VSMU-7-NPT/2004, into four breeds of Thai indigenous chicken, Phadu-Hung-Dang (PHD), Chee, Dang, and Luang-Hung-Khao (LHK), to explore effects of genetic background on host response. Among these breeds, Chee, Dang, and LHK showed significantly longer survival times than White Leghorns. Virus shedding from dead Thai indigenous chickens was significantly lower than that from White Leghorns. Although polymorphisms were observed in the <i>Mx</i> and MHC class I genes, there was no significant association between the polymorphisms in these loci and resistance to HPAIV.</p></div

Viral distribution in chickens infected with three HPAIVs at a dose of 10⁶ EID₅₀.

<p>Three chickens in each group were sacrificed at 24 h post-inoculation. Virus titers are presented as the mean values ± standard deviation. ⁑<i>P</i> < 0.01 vs. pigeon-04 and crane-05. ‡ <i>P</i> < 0.01 vs. crane-05.</p

Summary of the experimental infections at 10⁶EID₅₀.

<p>Summary of the experimental infections at 10⁶EID₅₀.</p

Comparison of the host gene responses in the lung, brain, and spleen in chickens infected with three HPAIVs.

<p>The level of mRNA expression of each gene was examined by real-time PCR analysis using specific to the corresponding gene. mRNA leveles indicate mean values ± standard deviations.</p

Lethality and viral shedding of five H5N1 HPAIVs.

<p>Survival curves of White Leghorns infected with five H5N1 HPAIVs at dosages of (A) 10⁴ EID₅₀ and (B) 10⁶ EID₅₀. Virus titers of trachea swabs (C) and cloacal swabs (D) obtained from dead White Leghorns infected with five HPAIVs at a dose of 10⁴ EID₅₀ (white columns) and 10⁶ EID₅₀ (gray columns). These swab samples were collected from the dead chickens immediately on the day of death. Virus titers are presented as the mean values ± standard deviation. * <i>P</i> < 0.05 vs. crane-05 (at 10⁴ EID₅₀). † <i>P</i> < 0.05 vs. pigeon-04 at a dose of 10⁶ EID₅₀. ⁑ <i>P</i> < 0.01 vs. openbill-6-04 at a dose of 10⁶ EID₅₀. § <i>P</i> < 0.05 vs. pigeon-04 and crane-05 at a dose of 10⁶ EID₅₀. ‡ <i>P</i> < 0.05 vs. crane-05, openbill-6-04, and pheasnt-05 at a dose of 10⁴ EID₅₀.</p

2012年から2016年にかけてナイジェリア南東部で検出されたラッサウイルスの遺伝学的解析

Lassa virus (LASV) is endemic in parts of West Africa where it causes Lassa fever (LF), a viral hemorrhagic fever with frequent fatal outcomes. The diverse LASV strains are grouped into six major lineages based on the geographical location of the isolated strains. In this study, we have focused on the lineage II strains from southern Nigeria. We determined the viral sequences from positive cases of LF reported at tertiary hospitals in Ebonyi and Enugu between 2012 and 2016. Reverse transcription-polymerase chain reaction (RT-PCR) showed that 29 out of 123 suspected cases were positive for the virus among which 11 viral gene sequences were determined. Phylogenetic analysis of the complete coding sequences of the four viral proteins revealed that lineage II strains are broadly divided into two genetic clades that diverged from a common ancestor 195 years ago. One clade, consisting of strains from Ebonyi and Enugu, was more conserved than the other from Irrua, although the four viral proteins were evolving at similar rates in both clades. These results suggested that the viruses of these clades have been distinctively evolving in geographically separate parts of southern Nigeria. Furthermore, the epidemiological data of the 2014 outbreak highlighted the role of human-to-human transmission in this outbreak, which was supported by phylogenetic analysis showing that 13 of the 16 sequences clustered together. These results provide new insights into the evolution of LASV in southern Nigeria and have important implications for vaccine development, diagnostic assay design, and LF outbreak management.長崎大学学位論文 学位記番号:博(医歯薬)甲第1107号 学位授与年月日:平成30年12月5日Author: Olamide K. Oloniniyi, Uche S. Unigwe, Sayaka Okada, Mayuko Kimura, Shota Koyano, Yukiko Miyazaki, Michael O. Iroezindu, Nnenna A. Ajayi, Chinedu M. Chukwubike, Nneka M. Chika-Igwenyi, Anne C. Ndu, Damian U. Nwidi, Haruka Abe, Shuzo Urata, Yohei Kurosaki, Jiro YasudaCitation: PLoS Neglected Tropical Diseases, 12(11), e0006971; 2018Nagasaki University (長崎大学)課程博