Host transcriptional response to persistent infection with a live-attenuated porcine reproductive and respiratory syndrome virus strain

Authors: CHAUDHARI, JAYESHBHAI - University Of Nebraska; LIEW, CHIA-SIN - University Of Nebraska; Workman, Aspen; RIETHOVEN, JEAN-JACK - University Of Nebraska; STEFFEN, DAVID - University Of Nebraska; SILLMAN, SARAH - University Of Nebraska; VU, HIEP L. X. - University Of Nebraska

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/24/2020
Publication Date: 7/28/2020
Citation: Chaudhari, J., Liew, C., Workman, A.M., Riethoven, J.M., Steffen, D., Sillman, S., Vu, H.L.X. 2020. Host transcriptional response to persistent infection with a live-attenuated porcine reproductive and respiratory syndrome virus strain. Viruses. 12(8):817. https://doi.org/10.3390/v12080817.
DOI: https://doi.org/10.3390/v12080817

Interpretive Summary: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen in pigs. Following acute infection, PRRSV can establish a “smoldering” type of persistent infection in lymphoid tissue, such as the lymph nodes and tonsil, that can last for months. The mechanisms of PRRSV persistence in these tissues remain poorly understood. Thus, the goal of this study was to gain insight into the putative mechanism by which PRRSV can evade host immune responses to establish persistent infection. An RNA sequencing approach was used to determine how PRRSV infection alters host gene expression in lymphoid tissue during persistent infection. This study revealed that PRRSV downregulated genes involved in the innate immune responses, including signaling molecules that recruit virus-specific immune cells to the site of infection. In contrast, genes that promote cell survival were upregulated. Together, this would allow the virus to keep infected cells alive and avoid detection and clearance by immune cells.

Technical Abstract: Both virulent and live-attenuated porcine reproductive and respiratory syndrome virus (PRRSV) strains can establish persistent infection in lymphoid tissues of pigs. To investigate the mechanisms of PRRSV persistence, we performed a transcriptional analysis of inguinal lymphoid tissue collected from pigs experimentally infected with an attenuated PRRSV strain at 46 days post infection. A total of 6404 differentially expressed genes (DEGs) were detected of which 3960 DEGs were upregulated and 2444 DEGs were downregulated. Specifically, genes involved in innate immune responses and chemokines and receptors associated with T-cell homing to lymphoid tissues were down regulated. As a result, homing of virus-specific T-cells to lymphoid tissues seems to be ineffective, evidenced by the lower frequencies of virus-specific T-cell in lymphoid tissue than in peripheral blood. Genes associated with T-cell exhaustion were upregulated. Likewise, genes involved in the anti-apoptotic pathway were upregulated. Collectively, the data suggested that the live-attenuated PRRSV strain establishes a pro-survival microenvironment in lymphoid tissue by suppressing innate immune responses, T-cell homing, and preventing cell apoptosis.