Immune Repertoire Diversity Correlated with Mortality in Avian Influenza A (H7N9) Virus Infected Patients.

Dongni Hou,Chunxue Bai,Jie Liu,Yuanlin Song,Tianlei Ying,Jieming Qu,Jian Han,Xinjun Tang,Zhiyong Zhang,Jianqing Xu,Tao Li,Chunlin Wang,Xiuhong Xi,Lili Wang,Qin Wang,Jian Zhou,Cuicui Chen,Miranda Byrne‐Steele ,E Scott Seeley ,Shuaiyao Lu

doi:10.1038/srep33843

Abstract

Specific changes in immune repertoires at genetic level responding to the lethal H7N9 virus are still poorly understood. We performed deep sequencing on the T and B cells from patients recently infected with H7N9 to explore the correlation between clinical outcomes and immune repertoire alterations. T and B cell repertoires display highly dynamic yet distinct clonotype alterations. During infection, T cell beta chain repertoire continues to contract while the diversity of immunoglobulin heavy chain repertoire recovers. Patient recovery is correlated to the diversity of T cell and B cell repertoires in different ways – higher B cell diversity and lower T cell diversity are found in survivors. The sequences clonally related to known antibodies with binding affinity to H7 hemagglutinin could be identified from survivors. These findings suggest that utilizing deep sequencing may improve prognostication during influenza infection and could help in development of antibody discovery methodologies for the treatment of virus infection.

Highlights

Effective humoral and cellular immune responses in influenza infection are critical for patient recovery from H7N9 infection[5,6,7,8]
From a total of 35 samples, deep sequencing based on Illimina MiSeq platform produced 150 base pairs surrounding the CDR3 of each T cell receptor βchain (TRB), and 250 base pairs covering CDR1 ~ 3 and beginning of C region of each Ig chain
The TRB repertoires presented a more stable pattern, with dominant clones conserved and constant part during the infection made up 23 ~ 61% of the whole repertoires (Fig. 1c,d). These results reveal the overwhelming variation as a property of IGH repertoire after H7N9 virus infection that differs from TRB repertoire

Summary

Introduction

Effective humoral and cellular immune responses in influenza infection are critical for patient recovery from H7N9 infection[5,6,7,8]. Immune repertoire analysis based on next-generation sequencing (NGS) is a novel approach to analyze alterations during the antiviral immune response[9,10,11]. In this study we explored alterations in the human immune repertoires after H7N9 infection. We identified antibody sequences from these NGS data. Direct insights into the immune response, especially distinct features of T cell and B cell repertoire behaviors, after human influenza A (H7N9) infection and suggest potential implications in antibody development and prognostication

Methods

Results

Conclusion