This week we profile a recent publication in The Journal of Infectious Diseases from Dr. Jessica Graham
(pictured, second from left) in the laboratory of Dr. Jennifer Lund (fourth from left) at Fred Hutch.
Can you provide a brief overview of your lab’s current research focus?
The focus of the Lund lab is on elucidating the basic mechanisms of anti-viral immunity and mucosal immunity using both mouse models as well as human tissues. Current projects include defining the roles and modes of action of tissue-resident memory T cells and regulatory T cells during mucosal virus infection, identifying novel mucosal immune correlates of protection from HIV-1 infection, and discovering new genes involved in immune responses to flavivirus infection, including both Zika and West Nile viruses. Overall, we hope that our studies will lead to improved clinical interventions for virus infections of public health importance.
What is the significance of the findingsĀ inĀ this publication?
We used a screen of genetically diverse mice from the Collaborative Cross (CC) mouse model infected with RNA viruses in combination with comprehensive pre-infection immunophenotyping to identify baseline immune correlates of protection from mortality to virus infection. Overall, our results define distinct T-cell correlates associated with survival following viral challenge. This study not only identifies specific basal immune characteristics that are associated with protection from mortality upon virus infections, but it also underscores the need for a protective immune response to be balanced in order to protect the host not only from uncontrolled virus replication but also from disease associated with robust immunity.
What are the next steps for this research?
Validation studies in humans are required to confirm these correlates of protection from severe clinical disease after virus infection, and the T-cell profile can inform methods by which to screen for individuals at increased risk of severe clinical disease upon virus infection. We will continue to use the CC mouse model to study immunity and clinical disease to infection in an animal model with diverse genotypes that better represent the large diversity in T-cell immunophenotypes represented in the human population.
This work was funded by:
This work was funded through a U19 grant from the National Institutes of Health (NIH).