PSU Profiles
Loading...
Keywords
Last Name
Institution

Rebecca Craven

TitleProfessor
InstitutionCollege of Medicine
DepartmentMicrobiology and Immunology
Address500 University Drive Hershey PA 17033
Mailbox: H107
Phone7175313528
vCardDownload vCard

    Collapse Overview 
    Collapse overview
    PREFERRED TITLE/ROLE:

    Professor of Microbiology and Immunology

    GRADUATE PROGRAM AFFILIATIONS:

    Biomedical Sciences options in Virology and Immunology and Biochemistry and Molecular Genetics, Intercollege Graduate Program in Genetics; MD/PhD Program.

    EDUCATION:

    Ph.D., University of Tennessee, Knoxville, 1981
    Postdoctoral Training, University of Alabama at Birmingham, 1981-1984

    NARRATIVE:

    The research in our laboratory is focused upon understanding the contributions of retroviral structural proteins to the virus life cycle. Retroviruses are agents of human and animal diseases, causing immunodeficiencies (including AIDS), leukemias, lymphomas, other malignancies, and wasting syndromes. Despite nearly a century of study, there are many gaps in our understanding of the basic processes of retroviral replication. Our laboratory specifically has focused upon the activities of the Gag protein in forming virus particles during the assembly phase of infection and of the CA protein in facilitating the early steps of genome replication.

    The CA protein is one of the least understood components of the retrovirus. It is well established that CA is the major structural element of the virus core. However, in addition, numerous studies indicate that its integrity is important for the events of genome replication, carried out by the reverse transcriptase enzyme packaged into the virion with the genome. There are, however, no adequate models to explain how it acts. We have conducted an extensive genetic analysis of CA function with a special focus on its most highly conserved amino acid motif. This work has indicated that this region of the protein is likely critical for its ability to assemble itself into a two-dimensional array of protein subunits known as the capsid shell. It also appears that these residues may participate in interactions with the reverse transcription complex in the interior of the capsid in a manner that is essential for effective genome replication. A major focus of our present work, therefore, is the dissection of the intermolecular interactions in which the CA protein is involved. This includes CA self-interaction to form the virus particle itself, interactions with host factors including the tryptophanyl tRNA synthetase, and the possible interaction of CA with other viral components of the reverse transcription complex (specifically viral RNA and reverse transcriptase). Genetic, biochemical, molecular biological and structural approaches will be used. Identification of the specific activities of CA will provide critical information needed for understanding the establishment of infection and oncogenesis by retroviruses, the transposition of retrotransposons and endogenous retroviruses in the human genome, and the mechanism of gene delivery by retroviral vectors. It may also provide a new target for the design of much-needed anti-retroviral strategies.


    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.
    List All   |   Timeline
    1. Jeon J, Qiao X, Hung I, Mitra AK, Desfosses A, Huang D, Gor'kov PL, Craven RC, Kingston RL, Gan Z, Zhu F, Chen B. Structural Model of the Tubular Assembly of the Rous Sarcoma Virus Capsid Protein. J Am Chem Soc. 2017 02 08; 139(5):2006-2013. PMID: 28094514.
      View in: PubMed
    2. Heyrana KJ, Goh BC, Perilla JR, Nguyen TN, England MR, Bewley MC, Schulten K, Craven RC. Contributions of Charged Residues in Structurally Dynamic Capsid Surface Loops to Rous Sarcoma Virus Assembly. J Virol. 2016 06 15; 90(12):5700-5714. PMID: 27053549.
      View in: PubMed
    3. Goh BC, Perilla JR, England MR, Heyrana KJ, Craven RC, Schulten K. Atomic Modeling of an Immature Retroviral Lattice Using Molecular Dynamics and Mutagenesis. Structure. 2015 Aug 04; 23(8):1414-25. PMID: 26118533; PMCID: PMC4526393.
    4. England MR, Purdy JG, Ropson IJ, Dalessio PM, Craven RC. Potential role for CA-SP in nucleating retroviral capsid maturation. J Virol. 2014 Jul; 88(13):7170-7. PMID: 24719425; PMCID: PMC4054415.
    5. Keller PW, Huang RK, England MR, Waki K, Cheng N, Heymann JB, Craven RC, Freed EO, Steven AC. A two-pronged structural analysis of retroviral maturation indicates that core formation proceeds by a disassembly-reassembly pathway rather than a displacive transition. J Virol. 2013 Dec; 87(24):13655-64. PMID: 24109217; PMCID: PMC3838239.
    6. Dalessio PM, Craven RC, Lokhandwala PM, Ropson IJ. Lethal mutations in the major homology region and their suppressors act by modulating the dimerization of the rous sarcoma virus capsid protein C-terminal domain. Proteins. 2013 Feb; 81(2):316-25. PMID: 23011855; PMCID: PMC3657841.
    7. Butan C, Lokhandwala PM, Purdy JG, Cardone G, Craven RC, Steven AC. Suppression of a morphogenic mutant in Rous sarcoma virus capsid protein by a second-site mutation: a cryoelectron tomography study. J Virol. 2010 Jul; 84(13):6377-86. PMID: 20427531; PMCID: PMC2903260.
    8. Purdy JG, Flanagan JM, Ropson IJ, Craven RC. Retroviral capsid assembly: a role for the CA dimer in initiation. J Mol Biol. 2009 Jun 05; 389(2):438-51. PMID: 19361521; PMCID: PMC2996723.
    9. Cardone G, Purdy JG, Cheng N, Craven RC, Steven AC. Visualization of a missing link in retrovirus capsid assembly. Nature. 2009 Feb 05; 457(7230):694-8. PMID: 19194444; PMCID: PMC2721793.
    10. Lokhandwala PM, Nguyen TL, Bowzard JB, Craven RC. Cooperative role of the MHR and the CA dimerization helix in the maturation of the functional retrovirus capsid. Virology. 2008 Jun 20; 376(1):191-8. PMID: 18433823; PMCID: PMC2474745.
    11. Purdy JG, Flanagan JM, Ropson IJ, Rennoll-Bankert KE, Craven RC. Critical role of conserved hydrophobic residues within the major homology region in mature retroviral capsid assembly. J Virol. 2008 Jun; 82(12):5951-61. PMID: 18400856; PMCID: PMC2395126.
    12. Heymann JB, Butan C, Winkler DC, Craven RC, Steven AC. Irregular and Semi-Regular Polyhedral Models for Rous Sarcoma Virus Cores. Comput Math Methods Med. 2008; 9(3-4):197-210. PMID: 19122884.
      View in: PubMed
    13. Butan C, Winkler DC, Heymann JB, Craven RC, Steven AC. RSV capsid polymorphism correlates with polymerization efficiency and envelope glycoprotein content: implications that nucleation controls morphogenesis. J Mol Biol. 2008 Feb 29; 376(4):1168-81. PMID: 18206161; PMCID: PMC2268030.
    14. Scheifele LZ, Kenney SP, Cairns TM, Craven RC, Parent LJ. Overlapping roles of the Rous sarcoma virus Gag p10 domain in nuclear export and virion core morphology. J Virol. 2007 Oct; 81(19):10718-28. PMID: 17634229; PMCID: PMC2045444.
    15. Spidel JL, Wilson CB, Craven RC, Wills JW. Genetic Studies of the beta-hairpin loop of Rous sarcoma virus capsid protein. J Virol. 2007 Feb; 81(3):1288-96. PMID: 17093186; PMCID: PMC1797520.
    16. Spidel JL, Craven RC, Wilson CB, Patnaik A, Wang H, Mansky LM, Wills JW. Lysines close to the Rous sarcoma virus late domain critical for budding. J Virol. 2004 Oct; 78(19):10606-16. PMID: 15367628; PMCID: PMC516377.
    17. Perez M, Craven RC, de la Torre JC. The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Proc Natl Acad Sci U S A. 2003 Oct 28; 100(22):12978-83. PMID: 14563923; PMCID: PMC240730.
    18. Cen S, Javanbakht H, Kim S, Shiba K, Craven R, Rein A, Ewalt K, Schimmel P, Musier-Forsyth K, Kleiman L. Retrovirus-specific packaging of aminoacyl-tRNA synthetases with cognate primer tRNAs. J Virol. 2002 Dec; 76(24):13111-5. PMID: 12438642; PMCID: PMC136713.
    19. Bowzard JB, Wills JW, Craven RC. Second-site suppressors of Rous sarcoma virus Ca mutations: evidence for interdomain interactions. J Virol. 2001 Aug; 75(15):6850-6. PMID: 11435564; PMCID: PMC114412.
    20. Xiang Y, Thorick R, Vana ML, Craven R, Leis J. Proper processing of avian sarcoma/leukosis virus capsid proteins is required for infectivity. J Virol. 2001 Jul; 75(13):6016-21. PMID: 11390603; PMCID: PMC114317.
    21. Cairns TM, Craven RC. Viral DNA synthesis defects in assembly-competent Rous sarcoma virus CA mutants. J Virol. 2001 Jan; 75(1):242-50. PMID: 11119594; PMCID: PMC113918.
    22. Parent LJ, Cairns TM, Albert JA, Wilson CB, Wills JW, Craven RC. RNA dimerization defect in a Rous sarcoma virus matrix mutant. J Virol. 2000 Jan; 74(1):164-72. PMID: 10590103; PMCID: PMC111525.
    23. Craven RC, Harty RN, Paragas J, Palese P, Wills JW. Late domain function identified in the vesicular stomatitis virus M protein by use of rhabdovirus-retrovirus chimeras. J Virol. 1999 Apr; 73(4):3359-65. PMID: 10074190; PMCID: PMC104100.
    24. Simpson SB, Guo W, Winistorfer SC, Craven RC, Stoltzfus CM. The upstream, direct repeat sequence of Prague A Rous sarcoma virus is deficient in mediating efficient Gag assembly and particle release. Virology. 1998 Jul 20; 247(1):86-96. PMID: 9683574.
      View in: PubMed
    25. Simpson SB, Zhang L, Craven RC, Stoltzfus CM. Rous sarcoma virus direct repeat cis elements exert effects at several points in the virus life cycle. J Virol. 1997 Dec; 71(12):9150-6. PMID: 9371572; PMCID: PMC230216.
    26. Craven RC, Parent LJ. Dynamic interactions of the Gag polyprotein. Curr Top Microbiol Immunol. 1996; 214:65-94. PMID: 8791725.
      View in: PubMed
    27. Pan W, Craven RC, Qiu Q, Wilson CB, Wills JW, Golovine S, Wang JF. Isolation of virus-neutralizing RNAs from a large pool of random sequences. Proc Natl Acad Sci U S A. 1995 Dec 05; 92(25):11509-13. PMID: 8524793; PMCID: PMC40431.
    28. Pepinsky RB, Papayannopoulos IA, Chow EP, Krishna NK, Craven RC, Vogt VM. Differential proteolytic processing leads to multiple forms of the CA protein in avian sarcoma and leukemia viruses. J Virol. 1995 Oct; 69(10):6430-8. PMID: 7666544; PMCID: PMC189543.
    29. Parent LJ, Bennett RP, Craven RC, Nelle TD, Krishna NK, Bowzard JB, Wilson CB, Puffer BA, Montelaro RC, Wills JW. Positionally independent and exchangeable late budding functions of the Rous sarcoma virus and human immunodeficiency virus Gag proteins. J Virol. 1995 Sep; 69(9):5455-60. PMID: 7636991; PMCID: PMC189393.
    30. Craven RC, Leure-duPree AE, Weldon RA, Wills JW. Genetic analysis of the major homology region of the Rous sarcoma virus Gag protein. J Virol. 1995 Jul; 69(7):4213-27. PMID: 7769681; PMCID: PMC189159.
    31. Weldon SK, Mosier DA, Simons KR, Craven RC, Confer AW. Identification of a potentially important antigen of Pasteurella haemolytica. Vet Microbiol. 1994 Jun; 40(3-4):283-91. PMID: 7941293.
      View in: PubMed
    32. Craven RC, Leure-duPree AE, Erdie CR, Wilson CB, Wills JW. Necessity of the spacer peptide between CA and NC in the Rous sarcoma virus gag protein. J Virol. 1993 Oct; 67(10):6246-52. PMID: 8396679; PMCID: PMC238047.
    33. Craven RC, Bennett RP, Wills JW. Role of the avian retroviral protease in the activation of reverse transcriptase during virion assembly. J Virol. 1991 Nov; 65(11):6205-17. PMID: 1717718; PMCID: PMC250313.
    34. Wills JW, Craven RC, Weldon RA, Nelle TD, Erdie CR. Suppression of retroviral MA deletions by the amino-terminal membrane-binding domain of p60src. J Virol. 1991 Jul; 65(7):3804-12. PMID: 1710290; PMCID: PMC241411.
    35. Wills JW, Craven RC. Form, function, and use of retroviral gag proteins. AIDS. 1991 Jun; 5(6):639-54. PMID: 1883539.
      View in: PubMed
    36. Bennett RP, Rhee S, Craven RC, Hunter E, Wills JW. Amino acids encoded downstream of gag are not required by Rous sarcoma virus protease during gag-mediated assembly. J Virol. 1991 Jan; 65(1):272-80. PMID: 1845888; PMCID: PMC240514.
    37. Wills JW, Craven RC, Achacoso JA. Creation and expression of myristylated forms of Rous sarcoma virus gag protein in mammalian cells. J Virol. 1989 Oct; 63(10):4331-43. PMID: 2550669; PMCID: PMC251050.
    Craven's Networks
    Click the "See All" links for more information and interactive visualizations!
    Concepts Expand Description
    _
    Co-Authors Expand Description
    _
    Similar People Expand Description
    _
    Same Department Expand Description
    Physical Neighbors Expand Description
    _