DeltaVP30 Ebola Virus Induces a Delayed and Attenuated Host Transcriptional Response

Abstract

Background:
The Ebola virus VP30 protein is essential for viral transcription, but its role in modulating host responses remains poorly understood. The deltaVP30 Ebola virus, which lacks VP30, is an attenuated strain being explored as a vaccine candidate. However, the temporal dynamics of the host transcriptional response to deltaVP30 infection have not been systematically characterized.

Methods:
We analyzed the public microarray data from human Huh cells infected with deltaVP30 Ebola virus or mock control at 0, 8, 24, 48, and 72 hours post-infection (n=5 per condition per time point; total 48 samples). Differential expression analysis (t-test with FDR correction), temporal clustering, and gene annotation were performed using Python in Google Colab.

Results:
At 24 hours post-infection, 6,105 probes showed statistically significant changes (adj_p < 0.05), but no probe exceeded a 1.5-fold change (max log2FC = 0.474, 1.39-fold). By 72 hours, the response amplified substantially, with 68 probes showing >1.5-fold changes (max log2FC = 0.965, 1.95-fold). Seventeen delayed response genes exhibited minimal change at 24 h but strong regulation at 72 h, including AREG (1.95-fold up), ANXA1 (1.70-fold up), GDF15 (1.66-fold up), SERPINC1 (1.58- fold down), and IL1RN (1.55-fold down). No classical interferon-stimulated gene signature was detected. Response magnitude increased significantly between 24 and 72 hours (p < 0.0001), with a low correlation between time points (ρ = 0.281).

Conclusions:
The deltaVP30 Ebola virus induces a delayed and attenuated host transcriptional response, with minimal changes at 24 h, followed by amplification by 72 h. The absence of a strong interferon signature and the delayed kinetics may suggest VP30 is critical for early modulation of host defenses.