Prusty BK, Hedau S, Singh A, Kar P, Das BC.. Selective suppression of NF-kBp65 in hepatitis virus-infected pregnant women manifesting severe liver damage and high mortality. Mol Med 13: 518-526

Division of Molecular Oncology, Institute of Cytology and Preventive Oncology, Noida, India.
Molecular Medicine (Impact Factor: 4.51). 09/2007; 13(9-10):518-26. DOI: 10.2119/2007-00055.Prusty
Source: PubMed


Fulminant hepatitis in Asian pregnant women is generally caused by hepatitis E virus infection, and extremely high mortality is most common in them. Decreased cell-mediated immunity is considered a major cause of death in these cases, but what exactly influences decreased immunity and high mortality specifically during pregnancy is not known. We used electrophoretic mobility shift assays, immunoblotting, and immunohistochemical analysis to study the expression and DNA binding activity of NF-kB p50 and NF-kB p65 in pregnant fulminant hepatic failure (FHF) patients and compared them with their nonpregnant counterparts. In both PBMC and postmortem liver biopsy specimens the DNA-binding activity of NF-kB was very high in samples from pregnant FHF patients compared with those from nonpregnant women as well as pregnant women with acute viral hepatitis (AVH) without FHF. Further dissection of the NF-kB complex in supershift assays demonstrated complete absence of p65 in the NF-kB complex, which is formed by homodimerization of the p50 component in pregnant FHF patients. Western blotting and immunohistochemical analysis of the expression of p50 and p65 proteins both showed higher levels of p50 expression and a complete absence or a minimal expression of p65, indicating its nonparticipation in NF-kB-dependent transactivation in pregnant FHF patients. We suggest that the exclusion of p65 from the NF-kB transactivation complex seems to be a crucial step that may cause deregulated immunity and severe liver damage, leading to the death of the patient. Our findings provide a molecular basis, for developing novel therapeutic approaches.

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    • "Hence it is important to understand the molecular mechanism by which HEV completes its life cycle inside the host. A recent study done by Prusty and coworkers revealed that NF-κB activity is inhibited in the PBMC and liver of fulminant hepatic failure patients [9]. Our findings that the ORF2 protein has the ability to inhibit NF-κB activity in human hepatoma cells provide a possible molecular explanation to their observation. "
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    BMC Biochemistry 05/2012; 13(1):7. DOI:10.1186/1471-2091-13-7 · 1.44 Impact Factor
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    • "This alteration in hormones may enhance viral replication, leading to severe liver disease during pregnancy [16]. Severe liver damage following HEV infection has also been correlated to the absence of NF-κB p65 subunit [17]. These observations suggest that the severity of HEV infection is influenced by the host response; identifying disease related host signatures would thus be important to understand disease pathogenesis and improving prognosis. "
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    • "NFκB is activated in the livers of subjects with chronic hepatitis C, and expression of RelA in these livers is associated with lower degree of apoptosis, and slower progression to fibrosisassociated chirrosis (Boya et al., 2001). Likewise, RelA expression is suppressed in pregnant women with chronic hepatitis E (HEV) infection and correlates with the severe liver damage and high mortality seen in these patients (Prusty et al., 2007). "
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