Project description:Viral pneumonia has been frequently reported during early stages of influenza virus pandemics and in many human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection. To better understand the pathogenesis of this disease, we produced non-lethal viral pneumonia in rhesus macaques by using an HPAI H5N1 virus (A/Anhui/2/2005; referred to as Anhui/2). Infected macaques were monitored for 14 days, and tissue samples were collected at 6 time points for virologic, histopathologic and transcriptomic analyses.
Project description:Reverse genetics has been widely used to investigate function of viral genes. In the present study we investigated the gene expression profile of a primary ovine cell (OFTu) in response to infection with the wild type (OV-IA82) and deletion mutant virus (OV-IA82Δ024) aiming to determine possible functions for ORFV024 during ORFV infection. We used microarray analysis to investigate gene expression profile of OFTu with ORFV OV-IA82 and OV-IA82Δ024.
Project description:Varicella pneumonia is the most common and severe complication of primary varicella-zoster virus (VZV) infection in adults. Pathogenesis of varicella pneumonia is largely unknown, mainly due to limited availability of clinical specimens and lack of appropriate VZV animal models. Simian varicella virus (SVV) infection of nonhuman primates closely recapitulates clinical and pathogenic features of human VZV disease. This study aimed to elucidate the virus and host factors that contribute to the pathogenesis of varicella pneumonia. The deposited data present changes in gene expression in the lung of SVV-infected cynomolgus macaques (Macaca fascicularis) at 3, 6 and 9 days after infection, and mock-infected control macaques at 3 days after infection.
Project description:Skeletal muscle dysfunction in survivors of pneumonia is a major cause of lasting morbidity that disproportionately affects older individuals. We found that skeletal muscle recovery was impaired in aged compared with young mice after influenza A virus-induced pneumonia. In young mice, recovery of muscle loss was associated with expansion of tissue-resident skeletal muscle macrophages and downregulation of MHC II expression, followed by a proliferation of muscle satellite cells. These findings were absent in aged mice and in mice deficient in Cx3cr1. Transcriptomic profiling of tissue-resident skeletal muscle macrophages from aged compared with young mice showed downregulation of pathways associated with phagocytosis and proteostasis, and persistent upregulation of inflammatory pathways. Consistently, skeletal muscle macrophages from aged mice failed to downregulate MHCII expression during recovery from influenza A virus induced pneumonia and showed impaired phagocytic function in vitro. Like aged animals, mice deficient in the phagocytic receptor Mertk showed no macrophage expansion, MHCII downregulation or satellite cell proliferation and failed to recover skeletal muscle function after influenza A pneumonia. Our data suggest that a loss of phagocytic function in a CX3CR1+ tissue-resident skeletal muscle macrophage population in aged mice precludes satellite cell proliferation and recovery of skeletal muscle function after influenza A pneumonia.
Project description:Viral pneumonia has been frequently reported during early stages of influenza virus pandemics and in many human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection. To better understand the pathogenesis of this disease, we produced non-lethal viral pneumonia in rhesus macaques by using an HPAI H5N1 virus (A/Anhui/2/2005; referred to as Anhui/2). Infected macaques were monitored for 14 days, and tissue samples were collected at 6 time points for virologic, histopathologic and transcriptomic analyses. Thirteen colony-bred male or female rhesus macaques (Macaca mulatta), aged from 2.5 to 3.5 years and ranging in weight from 2.8 to 4.4 kg, were used for experiments. Twelve macaques were individually infected intratracheally with 10^7 EID50 of Anhui/2 in 4 ml of phosphate-buffered saline (PBS). At 6 h, 12 h, 1 d, 3 d, 6 d, and 14 d post-infection (p.i.), two animals per time-point were euthanized under anesthesia and necropsies were performed. Lung samples were collected and stored in RNAlater (Ambion, Austin, USA) at -80M-BM-0C for RNA analyses. The remaining macaque (mock-infected) was inoculated with 4 ml of PBS intratracheally and euthanized at 6 h p.i. Lung tissues from the mock-infected animal were collected and stored as described.
Project description:In this work we generated a no-letal mice model infected with pandemic H1N1 virus in order to study the mechanisms implicated in the resolution of uncomplicated pneumonia by using gene expression profiles of lung tissues.
