Smc5/6 Antagonism by HBx Is an Evolutionarily Conserved Function of Hepatitis B Virus Infection in Mammals

Journal of Virology
Fabien AbdulLucie Etienne

Abstract

Chronic infection with hepatitis B virus (HBV) is a major cause of liver disease and cancer in humans. HBVs (family Hepadnaviridae) have been associated with mammals for millions of years. Recently, the Smc5/6 complex, known for its essential housekeeping functions in genome maintenance, was identified as an antiviral restriction factor of human HBV. The virus has, however, evolved to counteract this defense mechanism by degrading the complex via its regulatory HBx protein. Whether the antiviral activity of the Smc5/6 complex against hepadnaviruses is an important and evolutionarily conserved function is unknown. In this study, we used an evolutionary and functional approach to address this question. We first performed phylogenetic and positive selection analyses of the Smc5/6 complex subunits and found that they have been conserved in primates and mammals. Yet, Smc6 showed marks of adaptive evolution, potentially reminiscent of a virus-host "arms race." We then functionally tested the HBx proteins from six divergent hepadnaviruses naturally infecting primates, rodents, and bats. We demonstrate that despite little sequence homology, these HBx proteins efficiently degraded mammalian Smc5/6 complexes, independently of the host sp...Continue Reading

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Citations

Jun 7, 2019·Journal of Virology·Dmytro KornyeyevRudolf K Beran
Jun 7, 2019·Journal of Virology·Dhivya RamakrishnanSimon P Fletcher
Mar 19, 2020·Seminars in Immunopathology·Maura Dandri
Nov 6, 2020·Infection and Drug Resistance·Maura Dandri, Joerg Petersen
Jun 3, 2021·Microorganisms·Shimaa Hassan AbdelAziz SolimanFabio Verginelli
Sep 30, 2021·Experimental and Therapeutic Medicine·Yayun LinGuiqin Bai

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