Graduation Date

Fall 12-17-2021

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Immunology, Pathology & Infectious Disease

First Advisor

Santhi Gorantla

Second Advisor

Larisa Poluektova

Third Advisor

Rakesh Singh

Abstract

Studies on the pathogenesis of emerging viruses that present a global threat are critical for pathogen classification and therapeutic development. Humanized mice enable investigation of viral pathogens, including Human immunodeficiency virus (HIV-1), Zika virus (ZIKV), Coronavirus 2 (SARS-CoV-2), and Dengue virus (DENV), offering an advanced understanding into the mechanisms of viral perseverance in its natural human host cells and for therapeutic discovery. Realizing the diverse dynamics of various viral infections with the capacity to establish an innovative acuity for therapeutics and mechanics when utilizing humanized mice contributes a formerly inaccessible insight into human-specific viral pathogenesis and treatment. We recently developed a new and advanced humanized mouse model by co-transplanting human syngeneic neural progenitor cells (NPC). The employment of dual humanized mice permits the use of human-specific pathogens and allows us to study their interaction with re-created parts of the human immune system or human brain glia. We found that infection of dual humanized blood and brain mice with ZIKV resulted in high plasma viral loads with extensive dissemination observed primarily in the brain and spleen. The comprehensive repopulation with human astrocytes and the amplified infiltration of peripheral immune cells into the brain of dual reconstituted mice allowed insight into the role of astrocytes during viral infection. This novel mouse model explored the glial-neural-immune communications during ZIKV infection. Our model presents a strategic platform for investigating potential therapeutics to prevent or treat emerging viral infections with involvement of the central nervous system.

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