Abstract 3721: The transcriptional signature of KSHV infection in the guinea pig host

Introduction: Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human oncogenic virus implicated in various malignancies, including Kaposi’s sarcoma, primary effusion lymphoma, and Multicentric Castleman disease. The study investigates the similarities in gene expression profiles during KSHV infection of human and guinea pig lung cell lines, aiming to uncover conserved host responses and viral mechanisms across species. Methods: The human lung cell line MRC5 and guinea pig lung cell line JH4 are infected with KSHV and analyzed against non-infected cell lines as controls. RNA sequencing will be done using Illumina NovaSeq6000 platform. Raw data will be applied to the bioinformatic pipeline, which includes quality control with FastQC and MultiQC, adapter and quality trimming with Cutadapt, filtering to the genome of KSHV with STAR, transcript quantification with Salmon tool. Differential expressed genes will be identified using R package DESeq2 with FDR-adjusted p-value < 0.001 and absolute value of log2(FC) >1. Gene Ontology (GO) for functional annotation of genes and KEGG pathway analysis to determine difference in responses of intracellular pathways will be done. Expected Results: The RNA sequencing and transcriptome comparison between MRC5 and JH4 is expected to produce significant similarities in immune response and viral manipulation of cellular pathways. RNA sequencing should reveal an upregulation of interferon-stimulated genes (ISGs), and antiviral cytokines. Comparative transcriptomic analysis is expected to show a common pattern of dysregulation in genes related to cell cycle arrest, and apoptosis. Species-specific differences in the transcriptional regulation of metabolic pathways, as well as differences in cell-type-specific transcription factors are anticipated. This may influence the overall magnitude and nature of response to KSHV. Overall, this comparative study will enhance our understanding of KSHV-host interactions and could suggests the use of guinea pig as a viable model for KSHV research offering insights into conserved and species-specific antiviral defense mechanisms. Conclusion: Both human and guinea pig lung cell lines expected to exhibit similar activation of innate immune response genes, particularly interferon-stimulated genes and pro-inflammatory cytokines, highlighting a conserved antiviral defense response across species during KSHV infection. The similarity in gene expression profiles between human and guinea pig cell lines would be able to suggest that JH4 cells may serve as a viable model for studying KSHV infection, with minor species-specific differences providing additional insights into host-virus interactions. Citation Format: Kiran Fida, Mohammed Tanvir Hussain, Robert Ellis, Brent A. Stanfield. The transcriptional signature of KSHV infection in the guinea pig host [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3721.