Comparative Analysis of the effects of DM and NDM Strains of MHV on the Gap Junction intercellular communication protein Connexin 43 Expression and Trafficking

Sahu, Omkar (2023) Comparative Analysis of the effects of DM and NDM Strains of MHV on the Gap Junction intercellular communication protein Connexin 43 Expression and Trafficking. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Omkar Sahu (18MS007)) Thesis_18MS007.pdf - Submitted Version Restricted to Repository staff only Download (2MB)

Abstract

The Mouse Hepatitis Virus (MHV) is a type of coronavirus that has a predilection for infecting mice and is frequently employed as a model for investigating coronavirus infections. Prior research has indicated that infection with MHV has the potential to interfere with intercellular communication via gap junctions and modify the expression and transportation of connexins, specifically Cx43. Connexins are essential for maintaining normal physiological processes, and changes in their expression or activity have been linked to various pathological states. The change in gap junction expression, particularly Connexin 43, in response to viral stress has been the subject of investigation in both in vitro and in vivo studies involving neurons and oligodendrocytes. However, there exists an additional significant constituent of the pan glial syncytium (made up of neurons, oligodendrocytes, astrocytes and ependymocytes) which aids in the appropriate homeostasis and upkeep of the nervous system, namely the astrocytes. Prior research conducted in the laboratory has demonstrated that the infection of neuronal, oligodendrocyte cells and astocytic cells by the RSA59 as well as MHV-A59 virus leads to a reduction in the transportation of Gap Junction Connexin 43 (Cx43) from the endoplasmic reticulum to the plasma membrane. This, in turn, causes a decrease in the expression of Cx43 on the cells that have been infected by the virus. The impact of the other NDM virus strain, RSMHV2, and it’s parental strain MHV2, when infecting these astrocytes has yet to be explored in our laboratory. An unexplored area in viral infection research pertains to the differentiation between demyelinating and non-demyelinating models of Connexin43 expression. The viral strains MHVA-59 and MHV-2 present a promising opportunity to explore this uncharted area. The objective of this study is to conduct a comparative analysis of the impact of MHV-A59 or the demyelinating (DM) and MHV-2 or the non-demyelinating (NDM) strains of Mouse Hepatitis Virus (MHV) on the expression and trafficking of Cx43 in murine astrocytic cells. It has been observed that MHV strains of DM and NDM exhibit dissimilarities in their virulence and tissue tropism. Furthermore, these strains may have discrete impacts on gap junction intercellular communication and connexin expression, as reported in previous studies. Our research aims to elucidate the mechanisms responsible for the disruption of gap junction intercellular communication in coronavirus infection by examining the impact of DM and NDM strains of MHV on Cx43 expression and trafficking.

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