Publication Date

2019-01-17

Availability

Embargoed

Embargo Period

2021-01-16

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology (Medicine)

Date of Defense

2018-12-12

First Committee Member

Savita Pahwa

Second Committee Member

Suresh Pallikkuth

Third Committee Member

Santanu Banerjee

Fourth Committee Member

Enrique Mesri

Abstract

Aging and chronic HIV infection are known to independently affect the immune system and the microbiome, but what effect both have together is unknown. To investigate this effect we infected young and old Rhesus Macaques with simian immunodeficiency virus (SIV) and started on antiretroviral therapy (ART) at 84 days post infection. Blood and fecal samples were collected at pre SIV infection and various timepoints post-SIV infection. PBMCs were used for flow cytometry analysis of immune cell subsets, serum was used to determine influenza antibody titers and metabolites, and fecal samples were used for microbiome analysis. Analysis of samples before SIV infection showed that this non-human primate (NHP) model recaptured many of the ageassociated effects on host immunity and the microbiome as seen in reduced antibody response to immunization, increased plasma inflammatory response, alterations in immune cell subsets, and differences in relative abundance of microbial species. After SIV infection, many of the changes in immune subsets and plasma inflammatory response persisted, with increased differences in CD4 T naïve and central memory T cell subsets. Microbiome analysis showed the microbiome of young and old animals becomes more similar throughout SIV infection and the microbiome of young animals showed more capacity for change compared to the microbiome of old animals. Future studies will build upon this model to further explore changes in host immunity and the microbiome, including ongoing analysis of the relationship between vaccines and the microbiome.

Keywords

HIV; microbiome; aging

Available for download on Saturday, January 16, 2021

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