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iDEA: DREXEL LIBRARIES E-REPOSITORY AND ARCHIVES

iDEA: DREXEL LIBRARIES E-REPOSITORY AND ARCHIVES

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Age-like Phenotype of Microglia During HIV-1 Infection

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Title
Age-like Phenotype of Microglia During HIV-1 Infection
Author(s)
Chen, Natalie Cheng
Advisor(s)
Martin-Garcia, Julio
Keywords
Molecular biology; Cytology; Genetics; Biochemical Phenomena; Genetic Phenomena; Genetic Processes; Molecular biology; Cytology; Genetics
Date
2016-08-04
Publisher
Drexel University
Thesis
Ph.D., Molecular and Cell Biology and Genetics -- Drexel University, 2016
Abstract
HIV Associated Neurocognitive Disorder (HAND) persists in 50% of infected patients despite treatments. Moreover, HAND potentiates aging-associated neurocognitive decline as the infected population grow older. Microglia cells support productive HIV-1 infection in the brain and elevated senescence markers including p53 and p21 have been detected in microglia in HAND tissues. We hypothesize that HIV-1 induces age-like phenotypes in microglia. In an in vitro model of primary human microglia infected with HIV-1 pseudotype, we examined various markers of aging including the expression of cell cycle inhibitors (p53, p21 and p16), DNA damage associated p53 binding protein 1 (53BP1) foci formation, senescence associated [beta]-galactosidase (SA-[beta]-gal) activity, and the development of Senescence Associated Secretory Phenotype (SASP). Finally, we examined mitochondrial reactive oxygen species (ROS) and mitochondrial respiration, which are known to be altered during organismal aging. We detected elevated expression of p53 and p21, increased percentage of cells expressing 53BP1 foci and [beta]-gal, as well as significantly elevated levels of various cytokines including IL8 and IL6 post infection. The development of age-like phenotype is accompanied by increased mitochondrial ROS production and altered mitochondrial respiratory activity. Finally, exposure to the supernatant of infected microglia results in elevated p21 and caveolin-1 protein expression. Overall, we have demonstrated for the first time age-like phenotypes in human microglia during HIV-1 infection. HIV-1 induced microglial age-like phenotype could play a role in the development of HAND.
URI
http://hdl.handle.net/1860/idea:7160
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