The HDDC3 Knockout A-549 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population with disruption of the HDDC3 gene in the A-549 human lung adenocarcinoma cell line. This loss-of-function model enables investigation of HDDC3, an interferon-stimulated gene (ISG) and putative phosphohydrolase, in innate antiviral immunity. The polyclonal format provides a heterogeneous pool of cells edited by CRISPR/Cas9, suitable for functional genomics studies in a lung epithelial background.
The parental A-549 cell line, derived from a 58-year-old Caucasian male with lung carcinoma, exhibits adherent epithelial morphology and a KRAS G12S mutation. Widely used as a model for human alveolar Type II epithelial cells, A-549 cells support cancer biology, drug metabolism, and viral infection studies. Their susceptibility to respiratory pathogens, including influenza, RSV, and SARS-CoV-2, makes them relevant for innate immunity research. The KRAS oncogenic background further allows examination of crosstalk between oncogenic signaling and antiviral defenses.
HDDC3 is transcriptionally induced by type I interferons (IFN-??/??) via the JAK-STAT pathway. IFNAR engagement activates JAK1 and TYK2, which phosphorylate STAT1 and STAT2. These associate with IRF9 to form ISGF3, which translocates to the nucleus and drives ISG expression, including HDDC3. The protein restricts viral replication, likely through its predicted phosphohydrolase activity. HDDC3 interacts with MAVS and may modulate TBK1/IKK??-IRF3 signaling to amplify antiviral responses, contributing to innate immune effector gene expression.
In the KRAS-mutant A-549 lung adenocarcinoma context, HDDC3 knockout provides a unique tool to dissect cell-intrinsic antiviral pathways in epithelial cells. It allows exploration of how HDDC3 influences viral control, interferon sensitivity, and potential synergy with oncolytic virotherapy in cancer cells. This model bridges innate immunity and lung cancer biology by enabling host?Cpathogen interaction studies in a clinically relevant pulmonary cell type.
Applications include viral replication kinetics assays, interferon stimulation followed by RT-qPCR of ISG induction, and co-immunoprecipitation to confirm HDDC3-MAVS interactions. Additional uses encompass innate immune reporter assays, cell viability (MTT) under viral challenge, and immunofluorescence or flow cytometry for apoptosis. The polyclonal population also supports genetic rescue experiments. For further technical details, please contact Ascent Research.
