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Jianming Hu

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

 Overview 
 overview
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.



 Bibliographic 
 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. Cui X, Ludgate L, Ning X, Hu J. Maturation-associated destabilization of hepatitis B virus nucleocapsid. J Virol. 2013 Nov; 87(21):11494-503.
    View in: PubMed
  2. 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.
    View in: PubMed
  3. Jones SA, Hu J. Protein-primed terminal transferase activity of hepatitis B virus polymerase. J Virol. 2013 Mar; 87(5):2563-76.
    View in: PubMed
  4. 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.
    View in: PubMed
  5. 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.
    View in: PubMed
  6. 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.
    View in: PubMed
  7. Ludgate L, Adams C, Hu J. Phosphorylation state-dependent interactions of hepadnavirus core protein with host factors. PLoS One. 2011; 6(12):e29566.
    View in: PubMed
  8. 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.
    View in: PubMed
  9. 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.
    View in: PubMed
  10. 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.
    View in: PubMed
  11. 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.
    View in: PubMed
  12. 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.
    View in: PubMed
  13. Hu J, Lin L. RNA-protein interactions in hepadnavirus reverse transcription. Front Biosci (Landmark Ed). 2009; 14:1606-18.
    View in: PubMed
  14. Nguyen DH, Ludgate L, Hu J. Hepatitis B virus-cell interactions and pathogenesis. J Cell Physiol. 2008 Aug; 216(2):289-94.
    View in: PubMed
  15. 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.
    View in: PubMed
  16. 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.
    View in: PubMed
  17. Lin L, Hu J. Inhibition of hepadnavirus reverse transcriptase-epsilon RNA interaction by porphyrin compounds. J Virol. 2008 Mar; 82(5):2305-12.
    View in: PubMed
  18. 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.
    View in: PubMed
  19. 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.
    View in: PubMed
  20. Hu J, Ludgate L. HIV-HBV and HIV-HCV coinfection and liver cancer development. Cancer Treat Res. 2007; 133:241-52.
    View in: PubMed
  21. Basagoudanavar SH, Perlman DH, Hu J. Regulation of hepadnavirus reverse transcription by dynamic nucleocapsid phosphorylation. J Virol. 2007 Feb; 81(4):1641-9.
    View in: PubMed
  22. 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.
    View in: PubMed
  23. 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.
    View in: PubMed
  24. 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.
    View in: PubMed
  25. Hu J, Nguyen D. Therapy for chronic hepatitis B: the earlier, the better? Trends Microbiol. 2004 Oct; 12(10):431-3.
    View in: PubMed
  26. 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.
    View in: PubMed
  27. Perlman D, Hu J. Duck hepatitis B virus virion secretion requires a double-stranded DNA genome. J Virol. 2003 Feb; 77(3):2287-94.
    View in: PubMed
  28. 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.
    View in: PubMed
  29. 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.
    View in: PubMed
  30. Wang X, Grammatikakis N, Hu J. Role of p50/CDC37 in hepadnavirus assembly and replication. J Biol Chem. 2002 Jul 5; 277(27):24361-7.
    View in: PubMed
  31. 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.
    View in: PubMed
  32. 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.
    View in: PubMed
  33. Seeger C, Hu J. Why are hepadnaviruses DNA and not RNA viruses? Trends Microbiol. 1997 Nov; 5(11):447-50.
    View in: PubMed
  34. 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 2; 16(1):59-68.
    View in: PubMed
  35. 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.
    View in: PubMed
  36. 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 6; 93(3):1060-4.
    View in: PubMed
  37. Hu J, Seeger C. Expression and characterization of hepadnavirus reverse transcriptases. Methods Enzymol. 1996; 275:195-208.
    View in: PubMed
  38. 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.
    View in: PubMed
  39. 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.
    View in: PubMed
  40. 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.
    View in: PubMed
  41. Hu JM, Hsiung GD. Evaluation of new antiviral agents: I. In vitro perspectives. Antiviral Res. 1989 Jun-Jul; 11(5-6):217-32.
    View in: PubMed
  42. Zheng ZM, Zhang JH, Hu JM, Liu SF, Zhu WP. Poxviruses isolated from epidemic erythromelalgia in China. Lancet. 1988 Feb 6; 1(8580):296.
    View in: PubMed
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