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

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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.

No MeSH data available.


Related in: MedlinePlus

Dynamic change of IGH and TRB repertoires in an influenza A (H7N9) virus infected patient.(a,c) shows the overlap of IGH and TRB CDR3 sequences at different time points—11, 18, 25 and 42 days after symptom onset in patient H (survivor). (b,d) shows the dynamic changes of fractions of dominant IGH and TRB clones. Each CDR3 used a unique color. Width of each CDR3 clones stands for the fraction of this clone at each time point. CDR3 clones ranked top 5 in IGH repertories or top 20 in TRB were selected as representative dominant clones.
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f1: Dynamic change of IGH and TRB repertoires in an influenza A (H7N9) virus infected patient.(a,c) shows the overlap of IGH and TRB CDR3 sequences at different time points—11, 18, 25 and 42 days after symptom onset in patient H (survivor). (b,d) shows the dynamic changes of fractions of dominant IGH and TRB clones. Each CDR3 used a unique color. Width of each CDR3 clones stands for the fraction of this clone at each time point. CDR3 clones ranked top 5 in IGH repertories or top 20 in TRB were selected as representative dominant clones.

Mentions: An important feature of the immune response to foreign pathogens is clonal expansion of specific T and B cells and their subsequent contraction. To track the longitudinal immune repertoire dynamics in response to H7N9, we tried to collect sequential samples from these patients. For one of these patients, a total of four samples at different time points (11, 18, 25, and 42 days, respectively) were collected, while three or less were collected from others. During the disease progression, IGH repertoire of patient H showed typical alterations that are also found in other patients. The IGH sequences exceptionally high variation between time points (Fig. 1a), which shared sequences consisted only 0.6 ~ 20% of the whole repertoire. In addition, the dominant clones of IGH repertoires changes overtime (Fig. 1b), indicating that the consistent part of the IGH repertoire was very limited. In contrast, 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.


Immune Repertoire Diversity Correlated with Mortality in Avian Influenza A (H7N9) Virus Infected Patients
Dynamic change of IGH and TRB repertoires in an influenza A (H7N9) virus infected patient.(a,c) shows the overlap of IGH and TRB CDR3 sequences at different time points—11, 18, 25 and 42 days after symptom onset in patient H (survivor). (b,d) shows the dynamic changes of fractions of dominant IGH and TRB clones. Each CDR3 used a unique color. Width of each CDR3 clones stands for the fraction of this clone at each time point. CDR3 clones ranked top 5 in IGH repertories or top 20 in TRB were selected as representative dominant clones.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037391&req=5

f1: Dynamic change of IGH and TRB repertoires in an influenza A (H7N9) virus infected patient.(a,c) shows the overlap of IGH and TRB CDR3 sequences at different time points—11, 18, 25 and 42 days after symptom onset in patient H (survivor). (b,d) shows the dynamic changes of fractions of dominant IGH and TRB clones. Each CDR3 used a unique color. Width of each CDR3 clones stands for the fraction of this clone at each time point. CDR3 clones ranked top 5 in IGH repertories or top 20 in TRB were selected as representative dominant clones.
Mentions: An important feature of the immune response to foreign pathogens is clonal expansion of specific T and B cells and their subsequent contraction. To track the longitudinal immune repertoire dynamics in response to H7N9, we tried to collect sequential samples from these patients. For one of these patients, a total of four samples at different time points (11, 18, 25, and 42 days, respectively) were collected, while three or less were collected from others. During the disease progression, IGH repertoire of patient H showed typical alterations that are also found in other patients. The IGH sequences exceptionally high variation between time points (Fig. 1a), which shared sequences consisted only 0.6 ~ 20% of the whole repertoire. In addition, the dominant clones of IGH repertoires changes overtime (Fig. 1b), indicating that the consistent part of the IGH repertoire was very limited. In contrast, 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.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus