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Jianming Hu

TitleProfessor
InstitutionCollege of Medicine
DepartmentMicrobiology and Immunology
Address500 University Drive Hershey PA 17033
Mailbox: H107
Phone7175316523
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    PREFERRED TITLE/ROLE:

    Professor of Microbiology and Immunology

    GRADUATE PROGRAM AFFILIATIONS:

    Microbiology and Immunology, Cell and Molecular Biology, Genetics, MD/PhD Degree Program, Integrative Biosciences

    EDUCATION:

    M.D., Wuhan University School of Medicine, 1983
    Ph.D., Penn State University College of Medicine, 1993
    Post-doctoral Training, Yale University School of Medicine, 1987-1988
    Post-doctoral Training, Fox Chase Cancer Center, 1993-1997


    NARRATIVE:

    Hepatitis B virus (HBV) represents a significant human pathogen, with over 300 million people infected worldwide. Chronic HBV infection not only results in fatal liver diseases such as cirrhosis and liver failure but also dramatically increases the risk of liver cancer by over 100-fold. HBV infections present a fascinating system to study mechanisms of viral replication, virus-host interaction, and viral pathogenesis. HBV replicates a peculiar circular DNA genome via a reverse transcription pathway that is similar to, yet distinct from, that of retroviruses. The outcome of HBV infection ranges from transient, self-resolving acute hepatitis to life-long viral persistence with or without apparent liver pathology and its attendant sequelae. Viral clearance or persistence is clearly determined by the intricate interplay of a multitude of still largely undefined viral and host factors. We are focusing our studies on the virus-host interactions, at the molecular and cellular level, which are critical to HBV replication and pathogenesis.

    On the one hand, cellular factors required for viral assembly and replication are being sought using established cell-free as well as cell culture systems. We have identified some of the host factors required during the early stages of viral assembly and reverse transcription. We are continuing these studies in order to elucidate the requirements for the different stages of the viral replication cycle. A defining feature of HBV, as a pararetrovirus, is the fact that only the mature nucleocapsids containg the double-stranded DNA genome are enveloped and secreted extracellularly as virions, whereas the immature nucleocapsids containing the viral RNA or DNA intermediates are not secreted. We have recently discovered that viral reverse transcription and nucleocapsid maturation are coupled to virion secretion through dynamic phosphorylation and dephophorylation of the nucleocapsids. We are in the process of identifying the cellular factors responsible for this process and elucidating its regulation.

    On the other hand, we are seeking to identify host factors that may be involved in mediating the clearance of HBV infections, including cell intrinsic antiviral defense mechanism, which may suggest novel ways of curing HBV infections. Our recent results suggest the existence of cellular factors that can block the very early stage of viral assembly and reverse transcription and we are now pursuing the isolation of these cellular inhibitors of HBV replication. We have also obtained evidence that both the viral nucleocapsids and the episomal viral DNA genome are subject to intracellular turnover and we are in the process of elucidating these intracellular antiviral pathways.

    By focusing our efforts on the critical host factors that either positively or negatively affects viral replication, persistence and pathogenesis, we hope to eventually manipulate these factors therapeutically with novel antivirals, thus helping to control HBV infection and its deadly consequences. Furthermore, we hope to gain insights into the normal functions of these cellular factors by using viruses as tools.



    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Luo J, Cui X, Gao L, Hu J. Identification of Intermediate in Hepatitis B Virus CCC DNA Formation and Sensitive and Selective CCC DNA Detection. J Virol. 2017 Jun 21. PMID: 28637752.
      View in: PubMed
    2. Ning X, Basagoudanavar SH, Liu K, Luckenbaugh L, Wei D, Wang C, Wei B, Zhao Y, Yan T, Delaney W, Hu J. Capsid Phosphorylation State and Hepadnavirus Virion Secretion. J Virol. 2017 May 01; 91(9). PMID: 28228589.
      View in: PubMed
    3. Hu J, Liu K. Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application. Viruses. 2017 03 21; 9(3). PMID: 28335554.
      View in: PubMed
    4. Clark DN, Flanagan JM, Hu J. Mapping of Functional Subdomains in the Terminal Protein Domain of Hepatitis B Virus Polymerase. J Virol. 2017 Feb 01; 91(3). PMID: 27852858.
      View in: PubMed
    5. Clark DN, Jones SA, Hu J. In Vitro Assays for RNA Binding and Protein Priming of Hepatitis B Virus Polymerase. Methods Mol Biol. 2017; 1540:157-177. PMID: 27975315.
      View in: PubMed
    6. Li F, Cheng L, Murphy CM, Reszka-Blanco NJ, Wu Y, Chi L, Hu J, Su L. Minicircle HBV cccDNA with a Gaussia luciferase reporter for investigating HBV cccDNA biology and developing cccDNA-targeting drugs. Sci Rep. 2016 Nov 07; 6:36483. PMID: 27819342.
      View in: PubMed
    7. Ludgate L, Liu K, Luckenbaugh L, Streck N, Eng S, Voitenleitner C, Delaney WE, Hu J. Cell-Free Hepatitis B Virus Capsid Assembly Dependent on the Core Protein C-Terminal Domain and Regulated by Phosphorylation. J Virol. 2016 06 15; 90(12):5830-44. PMID: 27076641; PMCID: PMC4886785 [Available on 11/27/16].
    8. Cui X, Clark DN, Liu K, Xu XD, Guo JT, Hu J. Viral DNA-Dependent Induction of Innate Immune Response to Hepatitis B Virus in Immortalized Mouse Hepatocytes. J Virol. 2015 Oct 21; 90(1):486-96. PMID: 26491170; PMCID: PMC4702573.
    9. Clark DN, Hu J. Hepatitis B virus reverse transcriptase - Target of current antiviral therapy and future drug development. Antiviral Res. 2015 Nov; 123:132-7. PMID: 26408354; PMCID: PMC4639421 [Available on 11/01/16].
    10. Cui X, Luckenbaugh L, Bruss V, Hu J. Alteration of Mature Nucleocapsid and Enhancement of Covalently Closed Circular DNA Formation by Hepatitis B Virus Core Mutants Defective in Complete-Virion Formation. J Virol. 2015 Oct; 89(19):10064-72. PMID: 26202253; PMCID: PMC4577893.
    11. Hu J, Seeger C. Hepadnavirus Genome Replication and Persistence. Cold Spring Harb Perspect Med. 2015 Jul 01; 5(7):a021386. PMID: 26134841.
      View in: PubMed
    12. Cui X, Guo JT, Hu J. Hepatitis B Virus Covalently Closed Circular DNA Formation in Immortalized Mouse Hepatocytes Associated with Nucleocapsid Destabilization. J Virol. 2015 Sep; 89(17):9021-8. PMID: 26085156; PMCID: PMC4524059.
    13. Cui X, McAllister R, Boregowda R, Sohn JA, Cortes Ledesma F, Caldecott KW, Seeger C, Hu J. Does Tyrosyl DNA Phosphodiesterase-2 Play a Role in Hepatitis B Virus Genome Repair? PLoS One. 2015; 10(6):e0128401. PMID: 26079492; PMCID: PMC4469307.
    14. Clark DN, Hu J. Unveiling the roles of HBV polymerase for new antiviral strategies. Future Virol. 2015; 10(3):283-295. PMID: 25893003.
      View in: PubMed
    15. Liu K, Ludgate L, Yuan Z, Hu J. Regulation of multiple stages of hepadnavirus replication by the carboxyl-terminal domain of viral core protein in trans. J Virol. 2015 Mar; 89(5):2918-30. PMID: 25540387; PMCID: PMC4325754.
    16. Luckenbaugh L, Kitrinos KM, Delaney WE, Hu J. Genome-free hepatitis B virion levels in patient sera as a potential marker to monitor response to antiviral therapy. J Viral Hepat. 2015 Jun; 22(6):561-70. PMID: 25395045; PMCID: PMC4500509.
    17. Cao F, Jones S, Li W, Cheng X, Hu Y, Hu J, Tavis JE. Sequences in the terminal protein and reverse transcriptase domains of the hepatitis B virus polymerase contribute to RNA binding and encapsidation. J Viral Hepat. 2014 Dec; 21(12):882-93. PMID: 24401091; PMCID: PMC4090289.
    18. Jones SA, Clark DN, Cao F, Tavis JE, Hu J. Comparative analysis of hepatitis B virus polymerase sequences required for viral RNA binding, RNA packaging, and protein priming. J Virol. 2014 Feb; 88(3):1564-72. PMID: 24227865; PMCID: PMC3911602.
    19. Jones SA, Hu J. Hepatitis B virus reverse transcriptase: diverse functions as classical and emerging targets for antiviral intervention. Emerg Microbes Infect. 2013 Sep; 2(9):e56. PMID: 26038488; PMCID: PMC3820986.
    20. Cui X, Ludgate L, Ning X, Hu J. Maturation-associated destabilization of hepatitis B virus nucleocapsid. J Virol. 2013 Nov; 87(21):11494-503. PMID: 23966388; PMCID: PMC3807348.
    21. Jones SA, Murakami E, Delaney W, Furman P, Hu J. Noncompetitive inhibition of hepatitis B virus reverse transcriptase protein priming and DNA synthesis by the nucleoside analog clevudine. Antimicrob Agents Chemother. 2013 Sep; 57(9):4181-9. PMID: 23774432; PMCID: PMC3754288.
    22. Jones SA, Hu J. Protein-primed terminal transferase activity of hepatitis B virus polymerase. J Virol. 2013 Mar; 87(5):2563-76. PMID: 23255788; PMCID: PMC3571375.
    23. Ludgate L, Ning X, Nguyen DH, Adams C, Mentzer L, Hu J. Cyclin-dependent kinase 2 phosphorylates s/t-p sites in the hepadnavirus core protein C-terminal domain and is incorporated into viral capsids. J Virol. 2012 Nov; 86(22):12237-50. PMID: 22951823; PMCID: PMC3486511.
    24. Boregowda RK, Adams C, Hu J. TP-RT domain interactions of duck hepatitis B virus reverse transcriptase in cis and in trans during protein-primed initiation of DNA synthesis in vitro. J Virol. 2012 Jun; 86(12):6522-36. PMID: 22514346; PMCID: PMC3393569.
    25. Jones SA, Boregowda R, Spratt TE, Hu J. In vitro epsilon RNA-dependent protein priming activity of human hepatitis B virus polymerase. J Virol. 2012 May; 86(9):5134-50. PMID: 22379076; PMCID: PMC3347376.
    26. Ludgate L, Adams C, Hu J. Phosphorylation state-dependent interactions of hepadnavirus core protein with host factors. PLoS One. 2011; 6(12):e29566. PMID: 22216318; PMCID: PMC3245299.
    27. Meng D, Hjelm RP, Hu J, Wu J. A theoretical model for the dynamic structure of hepatitis B nucleocapsid. Biophys J. 2011 Nov 16; 101(10):2476-84. PMID: 22098746; PMCID: PMC3218330.
    28. Ning X, Nguyen D, Mentzer L, Adams C, Lee H, Ashley R, Hafenstein S, Hu J. Secretion of genome-free hepatitis B virus--single strand blocking model for virion morphogenesis of para-retrovirus. PLoS Pathog. 2011 Sep; 7(9):e1002255. PMID: 21966269; PMCID: PMC3178560.
    29. Boregowda RK, Lin L, Zhu Q, Tian F, Hu J. Cryptic protein priming sites in two different domains of duck hepatitis B virus reverse transcriptase for initiating DNA synthesis in vitro. J Virol. 2011 Aug; 85(15):7754-65. PMID: 21593164; PMCID: PMC3147914.
    30. Badtke MP, Khan I, Cao F, Hu J, Tavis JE. An interdomain RNA binding site on the hepadnaviral polymerase that is essential for reverse transcription. Virology. 2009 Jul 20; 390(1):130-8. PMID: 19467554; PMCID: PMC2737686.
    31. Heipertz RA, Starkey JL, Miller TG, Hu J, Isom HC. trans-Complementation of HBV rtM204I mutant replication by HBV wild-type polymerase. Virology. 2009 May 25; 388(1):57-67. PMID: 19383566; PMCID: PMC3670753.
    32. Hu J, Lin L. RNA-protein interactions in hepadnavirus reverse transcription. Front Biosci (Landmark Ed). 2009 Jan 01; 14:1606-18. PMID: 19273150; PMCID: PMC3611959.
    33. Nguyen DH, Ludgate L, Hu J. Hepatitis B virus-cell interactions and pathogenesis. J Cell Physiol. 2008 Aug; 216(2):289-94. PMID: 18302164; PMCID: PMC4386630.
    34. Nguyen DH, Hu J. Reverse transcriptase- and RNA packaging signal-dependent incorporation of APOBEC3G into hepatitis B virus nucleocapsids. J Virol. 2008 Jul; 82(14):6852-61. PMID: 18480459; PMCID: PMC2446951.
    35. Lin L, Wan F, Hu J. Functional and structural dynamics of hepadnavirus reverse transcriptase during protein-primed initiation of reverse transcription: effects of metal ions. J Virol. 2008 Jun; 82(12):5703-14. PMID: 18400846; PMCID: PMC2395161.
    36. Lin L, Hu J. Inhibition of hepadnavirus reverse transcriptase-epsilon RNA interaction by porphyrin compounds. J Virol. 2008 Mar; 82(5):2305-12. PMID: 18094191; PMCID: PMC2258913.
    37. Gao W, Hu J. Formation of hepatitis B virus covalently closed circular DNA: removal of genome-linked protein. J Virol. 2007 Jun; 81(12):6164-74. PMID: 17409153; PMCID: PMC1900077.
    38. Nguyen DH, Gummuluru S, Hu J. Deamination-independent inhibition of hepatitis B virus reverse transcription by APOBEC3G. J Virol. 2007 May; 81(9):4465-72. PMID: 17314171; PMCID: PMC1900192.
    39. Hu J, Ludgate L. HIV-HBV and HIV-HCV coinfection and liver cancer development. Cancer Treat Res. 2007; 133:241-52. PMID: 17672044.
      View in: PubMed
    40. Basagoudanavar SH, Perlman DH, Hu J. Regulation of hepadnavirus reverse transcription by dynamic nucleocapsid phosphorylation. J Virol. 2007 Feb; 81(4):1641-9. PMID: 17135319; PMCID: PMC1797568.
    41. Hu J, Boyer M. Hepatitis B virus reverse transcriptase and epsilon RNA sequences required for specific interaction in vitro. J Virol. 2006 Mar; 80(5):2141-50. PMID: 16474122; PMCID: PMC1395402.
    42. Perlman DH, Berg EA, O'connor PB, Costello CE, Hu J. Reverse transcription-associated dephosphorylation of hepadnavirus nucleocapsids. Proc Natl Acad Sci U S A. 2005 Jun 21; 102(25):9020-5. PMID: 15951426; PMCID: PMC1157036.
    43. Hu J, Flores D, Toft D, Wang X, Nguyen D. Requirement of heat shock protein 90 for human hepatitis B virus reverse transcriptase function. J Virol. 2004 Dec; 78(23):13122-31. PMID: 15542664; PMCID: PMC525004.
    44. Hu J, Nguyen D. Therapy for chronic hepatitis B: the earlier, the better? Trends Microbiol. 2004 Oct; 12(10):431-3. PMID: 15381188.
      View in: PubMed
    45. Wang X, Qian X, Guo HC, Hu J. Heat shock protein 90-independent activation of truncated hepadnavirus reverse transcriptase. J Virol. 2003 Apr; 77(8):4471-80. PMID: 12663754; PMCID: PMC152163.
    46. Perlman D, Hu J. Duck hepatitis B virus virion secretion requires a double-stranded DNA genome. J Virol. 2003 Feb; 77(3):2287-94. PMID: 12525667; PMCID: PMC140969.
    47. Guo JT, Pryce M, Wang X, Barrasa MI, Hu J, Seeger C. Conditional replication of duck hepatitis B virus in hepatoma cells. J Virol. 2003 Feb; 77(3):1885-93. PMID: 12525623; PMCID: PMC140889.
    48. Wang X, Hu J. Distinct requirement for two stages of protein-primed initiation of reverse transcription in hepadnaviruses. J Virol. 2002 Jun; 76(12):5857-65. PMID: 12021318; PMCID: PMC136195.
    49. Wang X, Grammatikakis N, Hu J. Role of p50/CDC37 in hepadnavirus assembly and replication. J Biol Chem. 2002 Jul 05; 277(27):24361-7. PMID: 11986322.
      View in: PubMed
    50. Hu J, Toft D, Anselmo D, Wang X. In vitro reconstitution of functional hepadnavirus reverse transcriptase with cellular chaperone proteins. J Virol. 2002 Jan; 76(1):269-79. PMID: 11739692; PMCID: PMC135730.
    51. Hu J, Anselmo D. In vitro reconstitution of a functional duck hepatitis B virus reverse transcriptase: posttranslational activation by Hsp90. J Virol. 2000 Dec; 74(24):11447-55. PMID: 11090140; PMCID: PMC112423.
    52. Seeger C, Hu J. Why are hepadnaviruses DNA and not RNA viruses? Trends Microbiol. 1997 Nov; 5(11):447-50. PMID: 9402701.
      View in: PubMed
    53. Hu J, Toft DO, Seeger C. Hepadnavirus assembly and reverse transcription require a multi-component chaperone complex which is incorporated into nucleocapsids. EMBO J. 1997 Jan 02; 16(1):59-68. PMID: 9009268; PMCID: PMC1169614.
    54. Seeger C, Leber EH, Wiens LK, Hu J. Mutagenesis of a hepatitis B virus reverse transcriptase yields temperature-sensitive virus. Virology. 1996 Aug 15; 222(2):430-9. PMID: 8806527.
      View in: PubMed
    55. Hu J, Seeger C. Hsp90 is required for the activity of a hepatitis B virus reverse transcriptase. Proc Natl Acad Sci U S A. 1996 Feb 06; 93(3):1060-4. PMID: 8577714; PMCID: PMC40030.
    56. Hu J, Seeger C. Expression and characterization of hepadnavirus reverse transcriptases. Methods Enzymol. 1996; 275:195-208. PMID: 9026639.
      View in: PubMed
    57. Hu J, Isom HC. Suppression of albumin enhancer activity by H-ras and AP-1 in hepatocyte cell lines. Mol Cell Biol. 1994 Mar; 14(3):1531-43. PMID: 8114691; PMCID: PMC358512.
    58. Hu JM, Camper SA, Tilghman SM, Miller T, Georgoff I, Serra R, Isom HC. Functional analyses of albumin expression in a series of hepatocyte cell lines and in primary hepatocytes. Cell Growth Differ. 1992 Sep; 3(9):577-88. PMID: 1419909.
      View in: PubMed
    59. Hu JM, Hsiung GD. Activities of two new antiviral agents against guinea pig lymphotropic herpesvirus infection in vitro. Antimicrob Agents Chemother. 1989 Sep; 33(9):1600-5. PMID: 2817855; PMCID: PMC172709.
    60. Hu JM, Hsiung GD. Evaluation of new antiviral agents: I. In vitro perspectives. Antiviral Res. 1989 Jun-Jul; 11(5-6):217-32. PMID: 2679375.
      View in: PubMed
    61. Zheng ZM, Zhang JH, Hu JM, Liu SF, Zhu WP. Poxviruses isolated from epidemic erythromelalgia in China. Lancet. 1988 Feb 06; 1(8580):296. PMID: 2893103.
      View in: PubMed
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