Unraveling the Mobilization and Interplay of Immune Cells in Rodent Hepacivirus Infection Restricted; Files Only

Abstract

Hepatitis C virus (HCV), a bloodborne pathogen known for causing liver inflammation and damage, presents a significant challenge to global health, particularly in the absence of a vaccine. This research delved into the study of rodent hepacivirus (RHV), a rodent analog of HCV, to unravel the complexities of HCV's pathogenesis. Utilizing KiKGR ROSA26 knock-in mice, capable of fluorescent cell labeling, we meticulously monitored the movements and behaviors of various immune cells during the course of infection. With a focus on the spleen as a crucial secondary lymphoid organ, we examined its role and subsequent effects on the liver post-infection (p.i.). Our findings revealed a plausible early infection influx of splenic innate cells and an accumulation of liver-resident monocytes (day 3 p.i.), followed by a heightened innate immune response characterized by a rise in liver-resident macrophages (day 7 p.i.), and later, an infiltration of splenic T cells and B cells, leading to an enhanced presence of CD8+ effector and memory cells in the liver (days 12 p.i.). Further insights from CCR2 knock-out mice indicated that CCR2+ monocytes/macrophages were not crucial in the virus' progression and clearance. This investigation enriched our understanding of immune responses in RHV infection and laid down a valuable groundwork for HCV research, potentially influencing future therapeutic strategies and vaccine development against viral diseases.

Table of Contents

1. INTRODUCTION ............................................................................................................1

2. MATERIALS AND METHODS .........................................................................................4 

1. KiKGR ROSA26 Knock-in Mice ...................................................................................4

2. Experiment 1 ..............................................................................................................4

3. Experiment 1 Techniques: Staining & Flow Cytometry .............................................5

4. CCR2 Knock-out Mice..................................................................................................6

5. Experiment 2 ...............................................................................................................6

3. RESULTS ..........................................................................................................................7

1. Day 3 Post Infection.....................................................................................................7

Figure 1.......................................................................................................................8

Figure 2.......................................................................................................................9

Figure 3.....................................................................................................................10

Figure 4.....................................................................................................................11

Figure 5.....................................................................................................................12

Figure 6.....................................................................................................................12

2. Day 7 Post Infection...................................................................................................13

Figure 7.....................................................................................................................14

Figure 8.....................................................................................................................16

Figure 9.....................................................................................................................17

Figure 10...................................................................................................................17

Figure 11...................................................................................................................18

3. CCR2 Knock-out Mice Data .......................................................................................18

Figure 12...................................................................................................................19

4. Day 12 Post Infection.................................................................................................19

Figure 13...................................................................................................................21

Figure 14...................................................................................................................22

Figure 15...................................................................................................................23

Figure 16...................................................................................................................24

Figure 17...................................................................................................................25

Figure 18...................................................................................................................26

Figure 19...................................................................................................................26

4. DISCUSSION ..................................................................................................................27

5. CONCLUSIONS ..............................................................................................................31

6. REFERENCES .................................................................................................................34

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Microbiology
Keyword	Immunology
Committee Chair / Thesis Advisor	Grakoui, Arash, Emory University
Committee Members	Thapa, Manoj, Emory University Jaeger, Dieter, Emory University

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