Impaired Virion Secretion by Hepatitis B Virus Immune Escape Mutants and Its Rescue by Wild-Type Envelope Proteins or a Second-Site Mutation |
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Authors: | Karen Kwei Xiaoli Tang Anna S. Lok Camille Sureau Tamako Garcia Jisu Li Jack Wands Shuping Tong |
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Affiliation: | aLiver Research Center, Rhode Island Hospital, Brown University, Providence, Rhode Island, USA;bDivision of Gastroenterology and Hepatology, University of Michigan Health Systems, Ann Arbor, Michigan, USA;cLaboratoire de Virologie Moleculaire, INTS, Paris, France |
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Abstract: | Hepatitis B virus immune escape mutants have been associated with vaccine failure and reinfection of grafted liver despite immune prophylaxis, but their biological properties remain largely unknown. Transfection of 20 such mutants in a human hepatoma cell line identified many with severe impairment in virion secretion, which can be rescued to various extents by coexpression of wild-type envelope proteins or introduction of a novel glycosylation site. Consistent with their role in maintaining intra- or intermolecular disulfide bonds, cysteine residues within the “a” determinant are critical for virion secretion. |
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