All ETDs from UAB

Advisory Committee Chair

Etty N Benveniste

Advisory Committee Members

Dale J Benos

Chenbei Chang

Avindra Nath

Phillip D Smith

David Sweatt

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Upon human immunodeficiency virus (HIV) infection the host mounts a robust and multifaceted immune response. To achieve successful replication, HIV must possess a powerful arsenal of immune evasion weapons. While a complex strategy for HIV immune evasion has been described in the periphery, little is known about the mechanism allowing HIV to overcome the simple interferon (IFN)-ß-mediated innate immune defenses of the central nervous system (CNS). In light of the devastating cognitive dysfunction that is caused by HIV replication within the CNS, a better understanding of this mechanism is critical. Recent studies have shown that viral pathogens can induce the expression of IFN signaling inhibitors known as Suppressors Of Cytokine Signaling (SOCS) proteins, and thereby escape immune attack. However, it is currently unknown whether SOCS proteins are induced in the HIV-infected brain, or whether they would be sufficient to overcome the antiviral effect of IFN-ß. In this dissertation, we first broadly review the role of virus-induced SOCS proteins in the promotion of viral replication. We then specifically describe a novel mechanism by which HIV can evade IFN-ß's antiviral effect in the CNS. Briefly, we show that HIV Tat-induced SOCS3 expression in macrophages diminishes IFN-ß signaling, ultimately preventing the ability of IFN-ß to inhibit HIV replication. These studies suggest that SOCS3 may promote cognitive dysfunction by allowing HIV to evade protective host immune responses in the CNS. In total, this dissertation explains the current state of the field concerning virally-induced SOCS proteins, and subsequently extends it with novel research findings describing the contribution of HIV Tat-induced SOCS3 to immune evasion in the CNS.



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