Keywords

Paramyxovirus, Persistent Infection, Complement, PIV5, C3, Complosome

Abstract

Persistent RNA virus infections (PI) are often characterized by extended viral shedding and maintained cycles of inflammation. We have an incomplete understanding of interactions between exogenous and cell intrinsic Complement (C') factors and paramyxovirus PI cells. Parainfluenza virus 5 (PIV5) acute infected (AI) cells can be recognized and lysed by exogenous C’ factors, but PI cells become resistant to C’-mediated lysis. We hypothesized that the relative sensitivity of AI and PI cells to C’ lysis is correlated with viral glycoprotein expression on the surface of cells. PI cells display lower levels of viral glycoprotein expression compared to AI cells. Pharmacological reduction of viral glycoprotein levels on AI cells to those on PI cells confers AI cells with resistance to C’ lysis, suggesting that C’ factors interact directly with viral glycoproteins. Recent complosome studies suggest a role for intracellular C’ in driving cell metabolism and regulating viability. After transition from an AI to a PI, cell intrinsic C3 is upregulated. We found that C3 knockout (KO) exacerbates the cell viability crisis as cells transition from an AI to a PI. Further, despite C3 KO cells having lower viral glycoprotein expression on AI cells, sensitivity to C’ lysis was increased in both AI and PI cells. C3 KO cells display greater baseline cell death and sensitivity to exogenous stressors, leading us to hypothesize that i) C3 facilitates the transition to a PI by regulating cell survival and ii) C3 KO cells become more sensitive to C’ due to increased cell stress. Our findings provide insight into the interactions of exogenous and cell intrinsic C’ with PI cells and their contribution to the establishment and maintenance of a PI. These results create a foundation for countering PIs by providing a deeper understanding of their mechanism of immune evasion and continued survival.

Completion Date

2026

Semester

Spring

Committee Chair

Griffith Parks

Degree

Doctor of Philosophy (Ph.D.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Format

PDF

Document Type

Dissertation

Identifier

DP0053105

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