Hepatitis B (HBV) Viral Important Structures Abbreviation Heparan Sulphate Proteoglycan HSPG + Human Na Taurocholate Co-Transporting Polypeptide Clathrin Rab5 Rab7 Numerical Name Localization HSPG Plasma Membrane NTCP NTCP Plasma Membrane --Rab5 Rab7 --Rab5 Rab7 Plasma Membrane Cytoplasm Cytoplasm Tubulin --- --- Cytoplasm Importin-β --- --- Nucleus Polymerase K POLK POLK Nucleus Polymerase (Reverse Trancscriptase) P, RT P, RT Virion Core Nxf1/Tap Nxf1/Tap Nfx1/Tap Nucleus (Shuttles In/Out to Cytoplasm) HBV Surface Antigen HBsAg HBsAg Virion Surface HBV Core Antibody anti-HBc anti-HBc Virion Core HBV Surface Antibody anti-HBs anti-HBs Virion Surface Relaxed Circular DNA rcDNA rcDNA Virion Core Covalently Closed Circular DNA cccDNA cccDNA Nucleus Subviral Particle SVP SVP Extracellular Matrix Pre-Genomic RNA pgRNA pgRNA Cytoplasm Large Surface Protein LHBs LS Plasma Membrane/MVBs Medium Surface Protein MHBs MS Plasma Membrane/MVBs Small Surface Protein SHBs SS Plasma Membrane/MVBs Core Protein HBe, HBc Hbe, HBc Virion Core Regulatory Protein HBx HBx Virion Core Interferon-α IFN-α IFN-α Cytoplasm CHMPs CHMPs (ESCRT-III) CHMPs 1, 2, 4 Cytoplasm/Plasma Membrane ALIX ALIX ALIX Cytoplasm/Plasma Membrane Direct Repeats 1 & 2 DR1, DR2 DR1, DR2 rcDNA/(-) Strand DNA Function Attachment Receptor for HBV; Interacts With SHBs A Liver-Specific Bile Acid Transporter (Host Function); Serves as the Cellular Receptor for HBV/HDV and Interacts with the PreS1 Domain of LHBs Serves Major Role in Formation of Cellular Vesicles and Virus Endocytosis Directs Vesicles from Plasma Membrane to Early Endosomes Directs/Develops Early Endosomes to Late Endosomes/Endo-Lysosomes Maintains Host Cell Structure and Provides a Platform for Intracellular Transport; Facilitates Efficient Shuttling of HBV cccDNA to the Nucleus A Nuclear Pore Protein that Transports the HBV Genome into the Nucleus by Binding to a NLS on the C-Terminus of the HBc Protein; The Viral Capsid Either 1) Disassembles Prior to Contact with Importin-β or 2) Capsid Destabilization Occurs as Capsid Travels Through Importin-β POLK is a Host DNA Pol that is Specifically Involved in DNA Repair; Carries Out Translesion Synthesis to Ligate the Gaps in Viral rcDNA, Converting it into cccDNA RDDP, DDDP, Helicase, RNaseH: Multifunctional Enzyme that Converts the Viral pgRNA into (-) Strand ssDNA Within the Immature Capsid (Traveling Through Cytoplasm); RT initiates Transcription at a Bulge in the pgRNA Near 5' End, Adds 3-4 NTs, 1st Strand Transfer; Translocate Synthesized NTs to DR1 Near 3' End of pgRNA, and Continues Elongation; pgRNA is Degraded While (-) Strand ssDNA Synthesis Takes Place; the (-) Strand DNA is Fully Synthesized and a Primer with a DR1 Seq. for (+) Strand DNA Synthesis is Created by RNaseH Activity Through Cleavage; Primer is Translocated From DR1 to DR2 and (+) Strand DNA is Initiated, Elongation Continues Until P Runs Out of Template, and DNA Molecule Circularizes; (+) Strand Anneals to 3' r of (-) Strand, Forming a Complete rcDNA HBV genome Mediates Nuclear Export of Host-Transcribed pgRNA; Nfx1/Tap Contains a NES and a NLS to Continually Shuttle In/Out of the Nucleus A Protein On the Surface of HBV virions and is Detectable in High Levels in Serum for Both Acute and Chronic HBV Infections; Presence Indicates an Individual is Infectious (INFECTED) An Antibody that Appears at the Onset of Symptoms in Acute HBV Infection and Persists for Life; Present in Both Acute and Chronic Infections (INFECTED) An Antibody Whose Presence Usually Indicates Recovery and Immunity From HBV Infection; anti-HBs Also Develops in Individuals Who Have Been Successfully Vaccinated Against HBV (No Longer Infected/Vaccinated) The Form of HBV's Small 3.2 kb Genome; It is Mostly dsDNA But Contains a ssDNA Gap With the 5' End of its (+) Strand Attached to a Tyr Residue in the P Pol and the 5' End of the (+) Strand Complement Joined to a Short, Capped RNA; the (+) Strand is Shorter than the (-) Strand, Due to Interuption of its Synthesis Before Completion (Causing the Single-Stranded Region); Both Strands are Held Together By H-Bonding Between the Short Repeat DR2 Sequences Present at Each 5' End rcDNA is Converted into this Covalently Closed Circular dsDNA Form: Occuring in the Host Nucleus Either By Viral P Protein or By Host Pols Through Extension of the (+) DNA Strand, Removal of Terminal Primers, and Covalent Ligation of the Resulting 3' and 5' Ends of Each DNA Strand; HBV cccDNA is Not Immediately Integrated into the Host Chromosome But Instead Remains in a Free, Circular Form, and the Viral Genome Gets Transcribed by Host RNA Pol II Into a Set of 5 mRNAs (1 of Which Also Serves as the pgRNA) High Concentrations of Subviral Particles Are Found in the Serum in Addition to the Complete Dane Particles, Either in a Spherical or Filamentous Shape; Spherical Particles Only Contain SHBs and MHBs While Filamentous Particles Also Contain LHBs, and Neither SVP Contains Any HBc, RT, or Viral Genome DNA; It is Believed that These SVPs Are Produced in Massive Amounts (100x-100,000x > Dane Particles) to Provide a "Stealth" Mechanism for Evading Host Immune Response, Causing Immune Antibodies to Bind/Complement the SVPs Instead of the LessAbundant Virions The Pre-Genomic RNA is the mRNA Transcript that Encodes the C and P Proteins, But it Also Serves as a Template to Produce the DNA Genome of HBV; Genome Synthesis From pgRNA Involves a Ribonucleoprotein Complex of pgRNA With Core and Polymerase Proteins LHBs is the Least Abundant Surface Protein Present in the HBV Virion and its Transcript is Exclusively Initiated From the PreS1 Promoter; Its PreS1 Domain Binds to Host NTCP Receptors and is Myristoylated at its N-Terminus Anchor; All HBs Are Involved in Envelope Formation and the Formation of SVPs Found in the Serum MHBs is HBV's 2nd-Most Abundant Surface Protein Whose Transcript is Initiated at the S Promoter, But Contains An Additional 55 N-Terminal AA's Not Present in SHBs; All HBs Are Involved in Envelope Formation and the Formation of SVPs Found in the Serum SHBs is the HBV's Small Surface Protein and it is Encoded By the Transcripts from the S Promoter; It is the Smallest and Most Abundant Surface Protein, and it Binds to the HSBGs Present on Host Cell Surfaces; All HBs Are Involved in Envelope Formation and the Formation of SVPs Found in the Serum The Core Proteins HBc is the Major Component of the Viral Nucleocapsid, Which Packages the the Viral Genome into the Mature Virion, and it Readily Dimerizes to Produce the Icosahedral Structure of the Nucleocapsid (T = 4); HBe is Translocated to the ER After Translation and its True Function is Still Unknown (It May Suppress the Host Immune System at High Levels and Prevent it From Eliminating Cells Containing HBV) HBx is the Virus' Regulatory Protein and it is Translated From the Shortest of the 5 Viral mRNAs; HBx is Not Found in Mature Virions or Nucleocapsids But it Stimulates Early Viral Gene Transcription; HBx Also Up-Regulates Multiple Proteins and Interacts With the Tumor Suppressor Protein p53 Host Immune Response Factor that Results in Hypoacetylation of cccDNA, Converting it into a Closed, Inactive Form, and Repressing Transcription Virus Release: Budding Detachment of the Virion inside of MVB/MVB-Derived Exosome Through Membrane Scission; Recruits VPS4 ATPases to Complete Membrane Fission Virus Release: ALIX is a Regulator of Capsid Budding that Also Mediates an ESCRTIndependent Pathway of HBV Egress Involving Naked Capsids DR1 is a 12 NT Direct Repeat Sequence On rcDNA of HBV that Serves as the Site of Translocation During 1st Strand Transfer of (-) Strand DNA Synthesis During Reverse Transcription; DR2 is a 12 NT Direct Repeat Sequence on the (-) Strand DNA and Serves as the Primer Site for Initiating (+) Strand DNA Synthesis; DR2 Sequences at Both 5' Ends Also Form the Hydrogen Bonding Between the 2 DNA Strands in the rcDNA Genome Origin Host Host Host Host Host Host Host Host Virus Host Virus Host Host Virus Virus Virus Virus Virus Virus Virus Virus Virus Host Host Host Virus