Defective Mitochondrial Quality Control during Dengue Infection Contributes to Disease Pathogenesis

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Mitochondrial quality control, including dynamics and mitophagy, is crucial for cellular health and implicated in diseases.
• Viral infections often target host mitochondria to promote viral replication and pathogenesis.

Purpose of the Study:

• To comprehensively analyze the impact of dengue virus infection on host mitochondrial homeostasis in liver cells.
• To elucidate the role of disrupted mitochondrial function in dengue disease pathogenesis.

Main Methods:

• Analysis of mitochondrial quality control and biogenesis pathways in dengue-infected human liver cells.
• Assessment of mitophagy flux and expression of key regulatory proteins (PINK1, Parkin, PPARγ, PGC1α).
• Detection of mitochondrial damage-associated molecular patterns (mtDAMPs) and their effect on immune cells.
• Correlation of in vitro findings with cell-free mitochondrial DNA levels in dengue patients.

Main Results:

• Dengue infection paradoxically downregulates mitochondrial quality control and biogenesis pathways despite severe mitochondrial stress.
• Mitophagy, including Parkin-dependent and independent pathways, is selectively inhibited.
• Dengue-infected cells release mtDAMPs, such as mitochondrial DNA, triggering proinflammatory signaling in naive immune cells.
• Elevated cell-free mitochondrial DNA levels in dengue patients correlate with thrombocytopenia.

Conclusions:

• Defective mitochondrial homeostasis in dengue-infected liver cells drives disease pathogenesis.
• Inhibition of mitochondrial quality control leads to damaged mitochondria accumulation, cellular injury, and release of inflammatory signals.
• Disruption of mitochondrial function by dengue virus contributes to systemic inflammation and disease severity.