aberrant cell cycle and apoptotic changes characterise severe influenza a infection – a meta-analysis of genomic signatures in circulating leukocytes异常的细胞周期和凋亡的变化描述严重流感感染u2014u2014一个荟萃分析的循环白细胞基因组签名.pdfVIP

Aberrant Cell Cycle and Apoptotic Changes Characterise Severe Influenza A Infection – A Meta-Analysis of Genomic Signatures in Circulating Leukocytes 1 1 2 1 1 1 Grant Parnell *, Anthony McLean , David Booth , Stephen Huang , Marek Nalos , Benjamin Tang 1 Department of Intensive Care Medicine, Western Clinical School, Nepean Hospital, University of Sydney, New South Wales, Australia, 2 Westmead Millennium Institute, University of Sydney, New South Wales, Australia Abstract Influenza A infection is a global disease that has been responsible for four pandemics over the last one hundred years. However, it remains poorly understood as to why some infected individuals succumb to life threatening complications whilst others recover and are relatively unaffected. Using gene-expression analysis of circulating leukocytes, here we show that the progression towards severe influenza A infection is characterised by an abnormal transcriptional reprogramming of cell cycle and apoptosis pathways. In severely infected humans, leukocyte gene-expression profiles display opposing cell cycle activities; an increased aberrant DNA replication in the G /S phase yet delayed progression in the G /M phase. In mild 1 2 infection, cell cycle perturbations are fewer and are integrated with an efficient apoptotic program. Importantly, the loss of integration between cell cycle perturbations and apoptosis marks the transition from a mild viral illness to a severe, life threatening infection. Our findings suggest that circulating immune cells may play a significant role in the evolution of the host response. Further study