The pre-S2 domain of the hepatitis B virus is dispensable for infectivity but serves a spacer function for L-protein-connected virus assembly

• Verfasst von: Ni, Yi [VerfasserIn]
• Verfasst von: Sonnabend, Jessika [VerfasserIn]
• Verfasst von: Seitz, Stefan [VerfasserIn]
• Verfasst von: Urban, Stephan [VerfasserIn]
• Titel: The pre-S2 domain of the hepatitis B virus is dispensable for infectivity but serves a spacer function for L-protein-connected virus assembly
• Verf.angabe: Yi Ni, Jessika Sonnabend, Stefan Seitz, and Stephan Urban
• E-Jahr: 2010
• Jahr: 3 February 2010
• Umfang: 10 S.
• Fussnoten: Gesehen am 15.05.2023
• Titel Quelle: Enthalten in: Journal of virology
• Ort Quelle: Baltimore, Md. : Soc., 1967
• Jahr Quelle: 2010
• Band/Heft Quelle: 84(2010), 8, Seite 3879-3888
• ISSN Quelle: 1098-5514
• DOI: doi:10.1128/JVI.02528-09
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1845369033

Abstract

The envelope of the human hepatitis B virus (HBV) contains three membrane proteins (L, M, and S). They accomplish different functions in HBV infectivity and nucleocapsid envelopment. Infectivity determinants have been assigned to the N-terminal part of the pre-S1 domain of the L protein and the antigenic loop of the S domain in the L and/or S protein. Nucleocapsid envelopment requires a C-terminal sequence within pre-S1, including the five N-terminal amino acids of pre-S2 as part of the L protein. However, the role of the M protein and the pre-S2 domain of the L protein are not entirely understood. We addressed this question and analyzed assembly competence and infectivity of viruses that lack the M protein and, at the same time, carry alterations in the pre-S2 domain of L. These include deletions, in part frameshift mutations and a randomization of virtually the entire pre-S2 sequence. We found that the M protein is dispensable for HBV in vitro infectivity. Viruses that lack the M protein and contain a mostly randomized pre-S2 sequence assemble properly and are infectious in HepaRG cells and primary human hepatocytes. While deletions of 20 amino acids in the pre-S2 domain of L protein allowed the production of infectious virions, more extended deletions interfered with assembly. This indicates that the pre-S2 domain of the L protein serves an important role for virus assembly, presumably as a spacer that supports conformational changes of L protein but does not participate as part of the M protein or as a subdomain of the L protein in virus entry.