Depressed Hypoxic and Hypercapnic Ventilatory Responses at Early Stage of Lethal Avian Influenza A Virus Infection in MiceReportar como inadecuado




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H5N1 virus infection results in ~60% mortality in patients primarily due to respiratory failure, but the underlying causes of mortality are unclear. The goal of this study is to reveal respiratory disorders occurring at the early stage of infection that may be responsible for subsequent respiratory failure and death. BALB-c mice were intranasally infected with one of two H5N1 virus strains: HK483 lethal or HK486 non-lethal virus. Pulmonary ventilation and the responses to hypoxia HVR; 7% O2 for 3 min and hypercapnia HCVR; 7% CO2 for 5 min were measured daily at 2 days prior and 1, 2, and 3 days postinfection dpi and compared to mortality typically by 8 dpi. At 1, 2, and 3 dpi, immunoreactivities IR of substance P SP-IR in the nodose ganglion or tyrosine hydroxylase TH-IR in the carotid body coupled with the nucleoprotein of influenza A NP-IR was examined in some mice, while arterial blood was collected in others. Our results showed that at 2 and 3 dpi: 1 both viral infections failed to alter body temperature and weight, , or induce viremia while producing similarly high lung viral titers; 2 HK483, but not HK486, virus induced tachypnea and depressed HVR and HCVR without changes in arterial blood pH and gases; and 3 only HK483 virus led to NP-IR in vagal SP-IR neurons, but not in the carotid body, and increased density of vagal SP-IR neurons. In addition, all HK483, rather than HK486, mice died at 6 to 8 dpi and the earlier death was correlated with more severe depression of HVR and HCVR. Our data suggest that tachypnea and depressed HVR-HCVR occur at the early stage of lethal H5N1 viral infection associated with viral replication and increased SP-IR density in vagal neurons, which may contribute to the respiratory failure and death.



Autor: Jianguo Zhuang , Peng Gao , Zemmie Pollock, Kevin S. Harrod, Fadi Xu

Fuente: http://plos.srce.hr/



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