The Hepato-modulatory role of Interferon-Induced protein with tetratricopeptide repeat2 (Ifit2) in MHV induced pathogenesis

Bhaduri, Sreetama (2025) The Hepato-modulatory role of Interferon-Induced protein with tetratricopeptide repeat2 (Ifit2) in MHV induced pathogenesis. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS Dissertation of Sreetama Bhaduri (20MS1095)) 20MS095_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (5MB)

Abstract

Interferon-induced protein with tetratricopeptide repeats 2 (Ifit2) is a protein that plays a very crucial role in restricting the neurotropic strain of the murine β-coronavirus, RSA59, by facilitating acute neuroinflammation, thereby aiding viral control and mitigating severe chronic demyelination. However, RSA59 also has a tropism for liver tissue, wherein viremia facilitates viral dissemination to the liver, thereby leading to hepatitis. Intracranial inoculation of RSA59 in the Ifit2 deficient (-/-) mice, as compared to wild-type (WT) mice, resulted in significant weight loss, exacerbated clinical symptoms, and reduced survival rates. Higher viral loads and elevated levels of interferons were observed in the Ifit2-deficient mice during the acute stage of the infection. The histopathological analysis has further revealed pronounced hepatic lesions, increased viral protein, and a phenotypic shift in the monocyte, macrophages, and tissue-resident Kupffer cells towards a phagocytic state in the liver of Ifit2 deficient mice. Despite the liver’s immune-privileged nature, the immune cells attempted to restore homeostasis. These observations have highlighted the pivotal antiviral role of Ifit2 in controlling the RSA59 infection and further focus on its therapeutic potential in mitigating hepato-neurotropic viral infection and related hepatic complications. Targeting Ifit2 pathways could serve as a novel strategy for enhancing host antiviral responses, reducing disease severity, and preventing chronic neurological and hepatic pathology.

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