title: Transbody against virus core protein potently inhibits hepadnavirus replication in vivo: evidence from a duck model of hepatitis B virus.
abstract: OBJECTIVE
  The therapeutic management of hepatitis B virus (HBV) infections remains challenging, and novel antiviral strategies are urgently required. The HBV transbody, a monoclonal antibody (MAb) against human HBcAg coupled with the trans-activator of transcription protein transduction domain (TAT PTD), was previously shown to possess cell-penetrating ability and potent antiviral activity in vitro. The purpose of the present study was to evaluate the antiviral activity of the HBcMAb-TAT PTD conjugate in vivo in a duck model of HBV.
  
  
  METHODS
  Female Peking ducks were injected i.p. with 0.03-0.3 mg·kg-1·day-1of the DHBV transbody (DHBcMAb-TAT PTD conjugate) for 30 days. Serum DHBV DNA levels and liver DHBV DNA and covalently closed circular DNA (cccDNA) loads were determined at scheduled time points. Immunohistological examination of DHBcAg in the duck liver was also performed.
  
  
  RESULTS
  The DHBV transbody significantly reduced the serum and liver DHBV DNA levels at doses of 0.1 and 0.3 mg·kg-1·day-1and liver cccDNA levels at a dose of 0.3 mg·kg-1·day-1after 30 days of treatment. The suppressive effects of the DHBV transbody at 0.3 mg·kg-1·day-1on the serum and liver DHBV DNA and liver cccDNA levels remained significant, even at 15 days after treatment cessation. Similarly, immunohistochemistry of liver sections revealed decreased DHBcAg levels within hepatocytes 15 days after treatment termination.
  
  
  CONCLUSIONS
  The DHBV transbody inhibits DHBV replication and possesses potent anti-DHBV activities in vivo. The cell-permeable antibody against the virus core antigen may be developed as a novel treatment for patients with hepadnavirus infections.
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.|Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, School of medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Hui
authors.affiliation: Department of Pathology, First Affiliated Hospital, School of medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, School of medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Feng
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, School of medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, School of medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: School of Computer Science and Engineering, Northwestern Polytechnical University, Xi'an, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Epidemiology and Statistics, School of medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Quanli
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Qunying
authors.initials: Q
authors.lastname: Han
authors.affiliation: Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi'an, China.|Department of Hepatobiliary Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Xi'an Hua Guang Biological Engineering Company, Xi'an, China.
authors.forename: Quanying
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Xi'an Hua Guang Biological Engineering Company, Xi'an, China.
authors.forename: Guangxiao
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, School of medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004279:DNA, Viral / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004372:Ducks / Q000821:virology*; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014758:Viral Core Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D004279:DNA, Viral; D014758:Viral Core Proteins