Characterizing Infection of B Cells with Wild-type and Vaccine Strains of Measles Virus Open Access
Melot, Logan (Spring 2023)
Abstract
Acute infection with measles virus (MeV) causes transient immunosuppression which can lead to secondary infections, which is not observed in vaccinated individuals. MeV infection of B lymphocytes leads to changes in the antibody repertoire and memory B cell populations for which the mechanism is unknown. We characterize the infection of primary B cells with wild-type (FL-15) and vaccine (EZ) strains of MeV. EZ-GFP infected cells are characterized by a higher percentage of cells positive for viral protein, regardless of B cell subtype. Cells infected with EZ-GFP displayed higher levels of N gene transcription at 24- and 48-hours post-infection than cells infected with FL-15. Non-switched memory cells had lower levels of viral protein expression than other subtypes during EZ-GFP infection. There were slightly higher levels of viral protein detected in non-switched memory cells than in other subtypes during FL-15 infection. Despite evidence of replication, measles-infected B cells did not produce detectable virus progeny. There are measurable differences in cell viability between FL-15 and EZ infected cultures. FL-15 infected culture had lower viability as well as higher levels of MLKL phosphorylation and cleavage of caspase-3, -8, and -9. Both FL-15 and EZ infected cultures had increased expression of IL-4 and IL-6. Higher levels of IL-8 were detectable in FL-15 infected cultures than in EZ infected cultures. Higher levels of TNF-α and IL-10 were detected in EZ compared to FL-15 infected cultures. Localization of nucleoprotein on the cell surface and at sites of cellular interaction were observed in both FL-15 and EZ infected cultures. Localization of hemagglutinin and MeV receptor SLAM were observed in both FL-15 and EZ infected cultures but protein reorganization occurred earlier in the infection in EZ infected cultures. These data help us understand the differences in viral replication and cellular outcome following infection with vaccine or wild-type strains of MeV.
Table of Contents
Chapter 1: Introduction (8-23)
- Virology of Measles Virus (8-11)
- History of Measles Vaccination (12-14)
- Measles Pathogenesis (14-15)
- Measles Symptoms (15-16)
- Measles and the Immune System (16-17)
- Measles Evasion of Host Response (17-20)
- In Vivo Infection of B cells (20-22)
- Differences in Vaccine and Wild-type Virus (22-23)
- Gaps in Knowledge (23)
Chapter 2: Characterizing Viral Replication During the Infection of B Cells with Wild-type or Vaccine Strains of Measles Virus (25-49)
- Introduction (25-27)
- Materials and Methods (27-31)
- Results (32-36)
- Discussion (36-39)
- Figures (40-49)
Chapter 3: Assessing Cellular Characteristics of B Cells Infected with Vaccine and Wild-type Strains of MeV (50-82)
- Introduction (52-55)
- Materials and Methods (55-61)
- Results (61-64)
- Discussion (64-70)
- Figures (71-82)
Chapter 4: Discussion and Conclusions (83-94)
- BJAB Cells as a Model of Infection for MeV (83-84)
- Comparison of Wild-type and Vaccine Replication in B Cells (84-86)
- Assessing Cell Death in MeV Infected B Cell Cultures Infected (86-87)
- Cytokine Expression in MeV Infected B Cell Cultures (87-88)
- Production of Viral Progeny and Non-canonical Viral Spread (88-91)
- Impact and Future Studies (91-93)
- Graphical Abstract (94)
References (95-102)
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