Conserved Yet Divergent Smc5/6 Complex Degradation by Mammalian Hepatitis B Virus X Proteins

TL;DR

This study explores how the X protein from a new cat hepatitis B virus affects the Smc5/6 complex in different host species, revealing both similarities and differences compared to human hepatitis B virus.

Contribution

The study reveals that the DCHBV X protein degrades the Smc5/6 complex in multiple species, with distinct mechanisms compared to human HBV.

Findings

The DCHBV X protein degrades the Smc5/6 complex in multiple host species.

Degradation of Smc6 by DCHBV X occurs independently of DDB1.

The anti-Smc5/6 activity of DCHBV X varies across host species.

Abstract

Hepatitis B virus (HBV), belonging to the genus Orthohepadnavirus, can cause chronic hepatitis and hepatocarcinoma in humans. HBV ensures optimal replication by encoding X, a multifunctional protein responsible for degrading the structural maintenance of chromosomes (Smc) 5/6 complex, an anti-HBV factor in hepatocytes. Previous studies suggest that degradation of the Smc5/6 complex is conserved among viruses from the genus Orthohepadnavirus. Recently, a novel hepadnavirus in cats, domestic cat HBV (DCHBV), has been identified as genetically close to HBV. However, it remains unclear whether the DCHBV X protein possesses similar Smc5/6 complex-degrading properties. Here, we investigated the degradation of the Smc5/6 complex by X proteins from viruses of the genus Orthohepadnavirus, including DCHBV, in cells derived from primates and cats. We found that the DCHBV X protein degraded the Smc5/6 complex in the cells of several host species, and the degree of its anti-Smc5/6 complex activity differed depending on the host species. Furthermore, the DCHBV X protein degraded Smc6 independently of DNA-binding protein 1 (DDB1), which is a critical host factor for HBV X-mediated Smc6 degradation. Our findings highlight the conserved yet divergent degradation machinery for Smc6 of mammalian hepatitis B virus X proteins.

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