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Rebecca Craven
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Title Professor
Institution College of Medicine
Department Microbiology and Immunology
Division Microbiology & Immunology
Address 500 University Drive Hershey PA 17033
 Mailbox: H107
Telephone 7175313528
Email
Background
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.
Publications
1. 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.
  View in: PubMed
 
2. 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.
  View in: PubMed
 
3. Purdy JG, Flanagan JM, Ropson IJ, Craven RC. Retroviral capsid assembly: a role for the CA dimer in initiation. J Mol Biol. 2009 Jun 5; 389(2):438-51.
  View in: PubMed
 
4. Cardone G, Purdy JG, Cheng N, Craven RC, Steven AC. Visualization of a missing link in retrovirus capsid assembly. Nature. 2009 Feb 5; 457(7230):694-8.
  View in: PubMed
 
5. 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.
  View in: PubMed
 
6. 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.
  View in: PubMed
 
7. 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.
  View in: PubMed
 
8. 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.
  View in: PubMed
 
9. 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.
  View in: PubMed
 
10. 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.
  View in: PubMed
 
11. 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.
  View in: PubMed
 
12. 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.
  View in: PubMed
 
13. 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.
  View in: PubMed
 
14. 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.
  View in: PubMed
 
15. Cairns TM, Craven RC. Viral DNA synthesis defects in assembly-competent Rous sarcoma virus CA mutants. J Virol. 2001 Jan; 75(1):242-50.
  View in: PubMed
 
16. 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.
  View in: PubMed
 
17. 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.
  View in: PubMed
 
18. 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.
  View in: PubMed
 
19. 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.
  View in: PubMed
 
20. Craven RC, Parent LJ. Dynamic interactions of the Gag polyprotein. Curr Top Microbiol Immunol. 1996; 214:65-94.
  View in: PubMed
 
21. 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 5; 92(25):11509-13.
  View in: PubMed
 
22. 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.
  View in: PubMed
 
23. 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.
  View in: PubMed
 
24. 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.
  View in: PubMed
 
25. 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.
  View in: PubMed
 
26. 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.
  View in: PubMed
 
27. 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.
  View in: PubMed
 
28. 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.
  View in: PubMed
 
29. Wills JW, Craven RC. Form, function, and use of retroviral gag proteins. AIDS. 1991 Jun; 5(6):639-54.
  View in: PubMed
 
30. Craven RC, Confer AW, Gentry MJ. Cloning and expression of a 30 kDa surface antigen of Pasteurella haemolytica. Vet Microbiol. 1991 Mar; 27(1):63-78.
  View in: PubMed
 
31. 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.
  View in: PubMed
 
32. 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.
  View in: PubMed
 
 
Keyword
Last Name
Institution
    
 
 
 
Keywords   
Virus Assembly
Avian Sarcoma Viruses
Capsid
Rous sarcoma virus
Capsid Proteins
See all (177) keywords
Co-Authors  
Dalessio, Paula
Flanagan, John
Parent, Leslie
Ropson, Ira
Wills, John
See all (5) people
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