Novel pathogenic characteristics of highly pathogenic avian influenza virus H7N9: viraemia and extrapulmonary infection

Abstract

The H7N9 virus mutated in 2017, resulting in new cases of highly pathogenic avian influenza (HPAI) H7N9 virus infection. H7N9 was found in a viraemic patient in Guangdong province, China. The present study aimed to clarify the pathogenic characteristics of HPAI H7N9. Virus was isolated from the plasma and sputum of the patient with HPAI H7N9. Liquid phase chip technology was used to detect the plasma cytokines from the infected patient and healthy controls. Mice were infected with strains A/Guangdong/GZ8H002/2017(H7N9) and A/Zhejiang/DTID-ZJU01/2013(H7N9) to observe the virus's pathogenic characteristics. Serum and brain tissue were collected at 2, 4, and 6 days after infection. The viruses in serum and brain tissue were detected and isolated. The two strains were infected into A549 cells, exosomes were extracted, and virus genes in the exosomes were assessed. Live virus was isolated from the patient's plasma. An acute cytokine storm was detected during the whole course of the disease. In animal experiments, A/Guangdong/GZ8H002/ 2017(H7N9) was more pathogenic than A/Zhejiang /DTID-ZJU01/2013(H7N9) and resulted in the death of mice. Live virus was isolated from infected mouse serum. Virus infection was also detected in the brain of mice. Under viral stress, A549 cells secreted exosomes containing the entire viral genome. The viraemic patient was confirmed to have an HPAI H7N9 infection. A/Guangdong/GZ8H002/2017(H7N9) showed significantly enhanced toxicity. Patient deaths might result from cytokine storms and brain infections. Extrapulmonary tissue infection might occur via the exosome pathway. The determined pathogenic characteristics of HPAI H7N9 will contribute to its future treatment.

COVID-19 update: Covid-19-associated coagulopathy

“…Infected A549 cells secreted exosomes containing the entire viral genome representing a potential mechanism for extrapulmonary infection. High serum levels of cytokines were detectable in patients and test animals [12,13].…”

The viral distribution and pathological characteristics of BALB/c mice infected with highly pathogenic Influenza H7N9 virus

“…The highly pathogenic H7N9 virus induced a more enhanced immune response than the low pathogenic H7N9 virus. Pathogenicity of high pathogenic H7N9 was increased by inducing a stronger cytokine storm [ 39 ]. The cause of death in mice is considered to be a result of increased replication capacity of highly pathogenic H7N9 virus, which is observed as rapid viral replication in lungs of mice on 3–4 dpi, the lung blood barrier breaking, viremia and other organs infection, later multi-organ infection and failure [ 39 ].…”

“…Pathogenicity of high pathogenic H7N9 was increased by inducing a stronger cytokine storm [ 39 ]. The cause of death in mice is considered to be a result of increased replication capacity of highly pathogenic H7N9 virus, which is observed as rapid viral replication in lungs of mice on 3–4 dpi, the lung blood barrier breaking, viremia and other organs infection, later multi-organ infection and failure [ 39 ]. It simultaneously induced a cytokine storm, resulting in multi-organ function impairment [ 39 ].…”

In Vivo Models to Study the Pathogenesis of Extra-Respiratory Complications of Influenza A Virus Infection

“…inoculation with HPAIVs, but also following i.n. inoculation with LPAIVs, mouse adapted IAVs, and pandemic IAV [ 61 , 77 , 78 , 79 ]. For example, viral RNA and infectious virus could be isolated from the blood, spleen, liver, and kidneys of HPAIV and LPAIV H7N9-inoculated mice [ 79 , 80 ].…”

“…inoculation with LPAIVs, mouse adapted IAVs, and pandemic IAV [ 61 , 77 , 78 , 79 ]. For example, viral RNA and infectious virus could be isolated from the blood, spleen, liver, and kidneys of HPAIV and LPAIV H7N9-inoculated mice [ 79 , 80 ]. Virus spread to extra-respiratory organs by virus isolation or by detection of viral antigen has been observed in the liver, pancreas, kidneys, spleen, and perivisceral fat tissue of HPAIV H5N1-inoculated mice [ 27 , 77 , 81 ], in the heart of IAV 2009 pH1N1-inoculated mice [ 57 , 61 ], and in the pancreas of mouse adapted IAV H1N1-inoculated mice [ 78 ].…”