Immune System Modulation of Genetic Diversity

Justification/Summary

How does the immune system modulate molecular evolution of West Nile virus in mammals?

A key unresolved question is how different aspects of the innate and adaptive immune response modulate the genetic diversity of West Nile virus within an animal or even, within a given tissue. As WNV pathogenicity and disease is similar between humans and a large number of animal species including rodents(28),infection of wild type inbred mice and congenic immunodeficient mice in combination with global genome sequencing will be used to address this question.  Three aspects of the immune response will be examined: 

Antibody-mediated immunity, CD8-T cell immunity, and IFN-ab immunity

People

Principal External Collaborator

Michael Diamond - Dept. of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO

Funding

Funding for this sequencing project was provided by the National Institute of Allergy and Infectious Diseases.

Cohort Description

b6wt_ip - Virus harvested at various time points either from serum (srm), spleen (sp), or brain (br) of wild-type C56BL6 mice infected intraperitoneally with cloned viral isolate WNV NY99.

b6wt_ic - Virus harvested at various time points either from serum (srm), spleen (sp), or brain (br) of wild-type C56BL6 mice infected intracranially with cloned viral isolate WNV NY99.

b6rag_ip - Virus harvested at various time points either from serum (srm), spleen (sp), or brain (br) of mice lacking mature B and T lymphocytes (RAG-1KO) that were infected intraperitoneally with cloned viral isolate WNV NY99.

b6rag_ic - Virus harvested at various time points either from serum (srm), spleen (sp), or brain (br) of mice lacking mature B and T lymphocytes (RAG-1KO) that were infected intracranially with cloned viral isolate WNV NY99.

b6ifn_ip - Virus harvested at various time points either from serum (srm), spleen (sp), or brain (br) of  interferon a/b receptor deficient mice (IFN-abR KO) infected intraperitoneally with cloned viral isolate WNV NY99.

b6ifn_ic - Virus harvested at various time points either from serum (srm), spleen (sp), or brain (br) of  interferon a/b receptor deficient mice (IFN-abR KO) infected intracranially with cloned viral isolate WNV NY99.

b6mMT_ip - Virus harvested at various time points either from serum (srm), spleen (sp), or brain (br) of  B-cell deficient mice (mMT) infected intraperitoneally with cloned viral isolate WNV NY99.

b6mMT_ic -  Virus harvested at various time points either from serum (srm), spleen (sp), or brain (br) of  B-cell deficient mice (mMT) infected intracranially with cloned viral isolate WNV NY99.