Comparative analysis of Mouse hepatitis virus-MHV-A59-induced hepatitis in Wild type, CD40L KO and CD40 KO mice

Gopinath, Gayathri (2023) Comparative analysis of Mouse hepatitis virus-MHV-A59-induced hepatitis in Wild type, CD40L KO and CD40 KO mice. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Gayathri Gopinath (18MS091)) Thesis_18MS091.pdf - Submitted Version Restricted to Repository staff only Download (6MB)

Abstract

Mouse hepatitis virus (MHV) is a βcoronavirus that can infect the rodent system and is known to cause hepatitis, encephalitis, and enteritis in mice. MHV-A59 is a hepato-neurotropic positive-stranded RNA virus and, as the name suggests, infects both the liver and the Central nervous system (CNS). Intracranial infection of MHV-A59 in 4–5-week-old C57BL/6 mice causes a biphasic disease. This is characterized by acute phase hepatitis and meningoencephalomyelitis and chronic phase axonal loss and demyelination, which mimic human MS symptoms. The intracranial inoculation of the virus causes a peak of inflammation at day 5, marked by hepatitis in the liver and meningitis, perivascular cuffing, and microglial nodule formation in the brain. Increased viral load causes the infiltration of peripheral immune cells to the CNS, subsequently leading to viral clearance primarily by CD4+ T cells. By controlling the activation of B cells, T cells, and APCs, as well as immune memory, CD40/CD40L interaction plays crucial roles in cellular and humoral immunity. A two-way signaling process between T cells and APCs is mediated by the CD40/CD40L molecular pair, in which the forward signal activates and differentiates T cells and B cells. In contrast, the reverse signal causes APCs to activate and differentiate. Post day 10, the liver tends to regenerate. The liver is a frontline immunological organ created with the particular purpose of identifying and eliminating possible infections from the blood while preserving overall immune hyperresponsiveness. A distinctive architecture, resident occupancy of essential immune cells, immunological surveillance, and quick recruitment are all necessary for the hepatic immune response. The relevance of this tissue as a critical immunological organ is highlighted by the liver's capacity to maintain the equilibrium between acute immune responses and tolerance. In this study, I have analyzed the effect of two immune responders, CD40L and CD40, in MHV-A59-induced hepatitis. For these two knockout strains of mice, CD40L KO and CD40 KO were used. Viral spread, hepatic lesion quantification, Kupffer cell migration, and proinflammatory cytokine and chemokine levels were analyzed in mock-infected and MHVA59-infected mice. This study showed that CD40L and CD40 absence doesn’t affect the liver pathology upon MHV-A59 infection intracranially when compared to wild type.

Actions (login required)

View Item