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HIV and Zika: modeling pathogenesis and therapies in humanized mice




Charlins, Paige, author
Akkina, Ramesh, advisor
Liber, Howard, committee member
Aboellail, Tawfik, committee member
Ryan, Elizabeth, committee member

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Investigation into pathogenesis of critical viral diseases that pose a global threat is important not only for pathogen modeling but also for treatment discovery. Use of humanized mice to study viral pathogens, including HIV-1 and Zika virus, provide a novel insight into the mechanisms of viral persistence and act as a platform for therapeutic intervention and observation. In the context of HIV-1 research, humanized mice are ideal for parroting the infection mechanics. Recapitulation of HIV-1 viral pathogenesis enables the study of various facets of the virus lifecycle, concerning infection establishment, detection, and treatment. In this respect, humanized mouse modeling of HIV-1 infection is paramount for continued studies of HIV-1 in terms of HIV-1 latency, with focus on viral reactivation and outgrowth, and for research with novel therapeutic approaches for treatment and modulation of the infection. The model has been paramount in development of an ultra-sensitive assay for detection of latent HIV-1 and validation of aptamer-siRNA conjugates and conditionally replicating vectors for treatment of HIV-1 infection. Humanized mice can further be expanded for the study of additional emerging pathogens, such as Zika virus, in terms of infection pathology and immune response. Infection of humanized mice with a Puerto Rican strain of Zika virus resulted in high plasma viral loads detectable up to four months post inoculation with wide spread dissemination detected in various tissues by IHC and CLARITY. Understanding these different elements of various viral infections with the ability to establish innovative perspective into mechanics and therapeutics, contribute a previously inaccessible view of human specific viral pathogenesis and treatment.


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