Keywords

Virology, Immunology, Innate, Complement, Persistent infections, Host–pathogen interaction, Immune evasion strategies, RNA viruses

Abstract

RNA viruses are a major global public health concern due to high mutation rates, zoonotic potential, and immune evasion. Parainfluenza virus 5 (PIV5) can establish persistent infections (PIs) despite encountering innate immune responses, including the complement (C′) system. RNA virus replication produces defective interfering particles (DIPs) containing truncated defective viral genomes (DVGs) that depend on standard (STD) virus for replication. DVGs are increasingly detected in natural infections and modulate type I interferon (IFN-I), but their role in the C′ system is unclear. We investigated how DVGs affect C′-mediated lysis during PIV5 infection using real-time in vitro cell viability assays. C′ killed human lung epithelial cells infected with STD PIV5, but co-infection with DIP-enriched virus suppressed killing. This required DVG replication and was independent of IFN-I. Increasing DI units showed a linear relationship between reduced surface viral glycoprotein expression and decreased C′-mediated lysis, suggesting DVGs alter susceptibility to C’ activation. We identified the Mitochondrial Antiviral-Signaling (MAVS) protein as a key host factor for evading C′. PIV5-infected wild-type (WT) A549 cells were initially C’ sensitive but established a PI, with ~25% resistant by day 2 and ~75% by day 4. MAVS-knockout (MAVS KO) cells showed higher viral gene expression, increased C3 and MAC deposition, greater susceptibility to C’-mediated killing, and failed to establish a PI. Ribavirin (RBV) restored long-term survival for the PIV5-infected MAVS KO cells, but these PI-like cells remained sensitive to C’-lysis. Together, these findings identify DVGs and MAVS as viral and host factors that influence C’ pathways and promote establishment of viral persistence.

Completion Date

2026

Semester

Spring

Committee Chair

Dr. Griffith Parks

Degree

Doctor of Philosophy (Ph.D.)

College

College of Medicine

Format

PDF

Document Type

Thesis

Identifier

DP0053109

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