Date of Completion

6-15-2020

Embargo Period

6-15-2021

Keywords

PRRSV, IL-10, STAT3, CD163, cryptotanshinone, PAM, PPIs, analogues

Major Advisor

Dr. Young Tang

Associate Advisor

Dr. Antonio E. Garmendia

Associate Advisor

Dr. Xiuchun (Cindy) Tian

Associate Advisor

Dr. Kristen Govoni

Associate Advisor

Dr. Mary Anne Amalaradjou

Field of Study

Animal Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is an economically significant panzootic affecting the swine industry worldwide. CD163 is the indispensable receptor for PRRS virus (PRRSV) infection and porcine alveolar macrophages (PAMs) are the principle target for productive PRRSV infection in pigs. We validated that the interleukin 10 (IL-10) stimulated Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signaling upregulates CD163 expression in pig cells. We identified a natural compound cryptotanshinone (Cpt) that inhibits IL-10-stimulated and basal level of CD163 expression in PAMs, and thus suppresses infection of PAMs by type I and type II PRRSV in vitro. In addition, we identified one synthetic compound disrupts protein-protein interactions (PPIs) between CD163 and PRRSV and that consequently inhibits infection of PAMs by type I and type II PRRSV. We also verified that some analogues of this active compound inhibit PRRSV infection of PAMs as well. We proposed 3-(morpholinosulfonyl)anilino moiety or 3-(piperidinylsulfonyl)anilino moiety could be pharmacophore important for the anti-PRRSV activity.

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