title: Hepatitis B virus surface antigen assembly function persists when entire transmembrane domains 1 and 3 are replaced by a heterologous transmembrane sequence.
abstract: Native hepatitis B surface antigen (HBsAg) spontaneously assembles into 22-nm subviral particles. The particles are lipoprotein micelles, in which HBsAg is believed to span the lipid layer four times. The first two transmembrane domains, TM1 and TM2, are required for particle assembly. We have probed the requirements for particle assembly by replacing the entire first or third TM domain of HBsAg with the transmembrane domain of HIV gp41. We found that either TM domain of HBsAg could be replaced, resulting in HBsAg-gp41 chimeras that formed particles efficiently. HBsAg formed particles even when both TM1 and TM3 were replaced with the gp41 domain. The results indicate remarkable flexibility in HBsAg particle formation and provide a novel way to express heterologous membrane proteins that are anchored to a lipid surface by their own membrane-spanning domain. The membrane-proximal exposed region (MPER) of gp41 is an important target of broadly reactive neutralizing antibodies against HIV-1, and HBsAg-MPER particles may provide a good platform for future vaccine development.
authors.affiliation: Center for Biologics, FDA, Bethesda, MD 20892, USA. ira.berkower@fda.hhs.gov
authors.forename: Ira
authors.initials: I
authors.lastname: Berkower
authors.forename: Angelo
authors.initials: A
authors.lastname: Spadaccini
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Danah
authors.initials: D
authors.lastname: Al-Awadi
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Muller
authors.forename: Yamei
authors.initials: Y
authors.lastname: Gao
authors.forename: Dino
authors.initials: D
authors.lastname: Feigelstock
authors.forename: Konstantin
authors.initials: K
authors.lastname: Virnik
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Ni
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D006509:Hepatitis B / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017434:Protein Structure, Tertiary
chemical_list: D006514:Hepatitis B Surface Antigens