.

Department of Pathology, Microbiology, and Immunology

 

 

Christopher R. Aiken, Ph.D.a

 

 

Professor

Dept. of Pathology, Microbiology and Immunology

 

 

Contact Information

 

 

Office Location:
MCN AA-5230A;

Phone: 615-343-7037
E-mail:  chris.aiken@vanderbilt.edu

                     

Campus Mail Address:

Pathology, Microbiology and Immunology-5th Fl

MCN -A 5301 (2363)

 

US Mailing Address:
Vanderbilt University School of Medicine

Dept of Pathology, Microbiology and Immunology-5th Fl
MCN A-5301
Nashville, TN 37232-2363

 

 

 

Education

 

 

Postdoctoral Studies, Salk Institute for Biological Studies
Ph.D., University of Illinois, Urbana-Champaign
B.S., University of California, Santa Barbara

 

 

Research Keywords

 

 

Infectious disease, Microbiology, Virus, HIV

 

 

Research Description

 

 

The focus of the Aiken lab is to understand the molecular events governing HIV replication in order to develop novel antiviral therapies. We use the tools of biochemistry, molecular biology, and cell biology to study virus-host cell interactions. We also collaborate with structural biologists to understand the structure and function of the viral capsid. We are particularly interested in interactions between virus and host cell proteins. Current projects include:
1. HIV-1 capsid structure and function (Cell 139:780-90, 2009; Nature 497:643-6, 2013).
2. Role of host cell proteins in HIV-1 infection (J. Virol. 82:12001-8, 2008; J. Virol. 87:422-32, 2013).
3. Mechanism of HIV-1 restriction by TRIM5alpha (PLos Pathog. 4(5):e1000074, 2008; J. Virol. 84:6564-69, 2010; PLos Path 7:e1002009, 2011; J. Virol. 87:9271-8, 2013).
4. Identification and mechanisms of HIV-1 capsid inhibitors (J. Virol. 85:542-9, 2011).
5. Conformational Masking of HIV-1 Env proteins during virion maturation (PLoS Pathog 7:e1002234, 2011).

 

 

Publications

 

 

Henning, MS, Dubose, BN, Burse, MJ, Aiken, C, Yamashita, M. In Vivo Functions of CPSF6 for HIV-1 as Revealed by HIV-1 Capsid Evolution in HLA-B27-Positive Subjects. PLoS Pathog, 10(1), e1003868, 2014

Yufenyuy, EL, Aiken, C. The NTD-CTD intersubunit interface plays a critical role in assembly and stabilization of the HIV-1 capsid. Retrovirology, 10, 29, 2013

Shah, VB, Shi, J, Hout, DR, Oztop, I, Krishnan, L, Ahn, J, Shotwell, MS, Engelman, A, Aiken, C. The Host Proteins Transportin SR2/TNPO3 and Cyclophilin A Exert Opposing Effects on HIV-1 Uncoating. J Virol, 87(1), 422-32, 2013

Shi, J, Friedman, DB, Aiken, C. Retrovirus restriction by TRIM5 proteins requires recognition of only a small fraction of viral capsid subunits. J Virol, 87(16), 9271-8, 2013

Yu Z, Dobro MJ, Woodward CL, Levandovsky A, Danielson CM, Sandrin V, Shi J, Aiken C, Zandi R, Hope TJ, Jensen GJ. Unclosed HIV-1 capsids suggest a curled sheet model of assembly. J. Mol. Biol. , 425, 112-23, 2013

Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning Y, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature, 497(7451), 643-46, 2013

Yang H, Ji X, Zhao G, Ning J, Zhao Q, Aiken C, Gronenborn AM, Zhang P, Xiong Y. Structural insight into HIV-1 capsid recognition by rhesus TRIM5??. Proc Natl Acad Sci USA, 109, 18372-7, 2012

Yang, R, Shi, J, Byeon, IJ, Ahn, J, Sheehan, JH, Meiler, J, Gronenborn, AM, Aiken, C. Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Retrovirology, 9, 30, 2012

Shi, J, Zhou, J, Shah, VB, Aiken, C, Whitby, K. Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization. J Virol, 85(1), 542-9, 2011

Zhao, G, Ke, D, Vu, T, Ahn, J, Shah, VB, Yang, R, Aiken, C, Charlton, LM, Gronenborn, AM, Zhang, P. Rhesus TRIM5I? disrupts the HIV-1 capsid at the inter-hexamer interfaces. PLoS Pathog, 7(3), e1002009, 2011

Du, S, Betts, L, Yang, R, Shi, H, Concel, J, Ahn, J, Aiken, C, Zhang, P, Yeh, JI. Structure of the HIV-1 full-length capsid protein in a conformationally trapped unassembled state induced by small-molecule binding. J Mol Biol, 406(3), 371-86, 2011

Joyner AS, Willis J, Crowe Jr. JE, Aiken C. Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles. PLoS Pathog, 9, e1002234, 2011

Shah, VB, Aiken, C. In vitro uncoating of HIV-1 cores. J Vis Exp(57), 2011

Joyner, AS, Willis, JR, Crowe, JE, Aiken, C. Maturation-induced cloaking of neutralization epitopes on HIV-1 particles. PLoS Pathog, 7(9), e1002234, 2011

Black, LR, Aiken, C. TRIM5alpha disrupts the structure of assembled HIV-1 capsid complexes in vitro. J Virol, 84(13), 6564-9, 2010

Matei, E, Zheng, A, Furey, W, Rose, J, Aiken, C, Gronenborn, AM. Anti-HIV activity of defective cyanovirin-N mutants is restored by dimerization. J Biol Chem, 285(17), 13057-65, 2010

Shah, VB, Aiken, C. HIV Nuclear Entry: Clearing the Fog. Viruses, 2(5), 1190-4, 2010

Aiken, C. Cell-free assays for HIV-1 uncoating. Methods Mol Biol, 485, 41-53, 2009

Byeon, IJ, Meng, X, Jung, J, Zhao, G, Yang, R, Ahn, J, Shi, J, Concel, J, Aiken, C, Zhang, P, Gronenborn, AM. Structural convergence between Cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function. Cell, 139(4), 780-90, 2009

Langelier, CR, Sandrin, V, Eckert, DM, Christensen, DE, Chandrasekaran, V, Alam, SL, Aiken, C, Olsen, JC, Kar, AK, Sodroski, JG, Sundquist, WI. Biochemical characterization of a recombinant TRIM5alpha protein that restricts human immunodeficiency virus type 1 replication. J Virol, 82(23), 11682-94, 2008

Qi, M, Aiken, C. Nef enhances HIV-1 infectivity via association with the virus assembly complex. Virology, 373(2), 287-97, 2008

Rold, CJ, Aiken, C. Proteasomal degradation of TRIM5alpha during retrovirus restriction. PLoS Pathog, 4(5), e1000074, 2008

Qi, M, Yang, R, Aiken, C. Cyclophilin A-dependent restriction of human immunodeficiency virus type 1 capsid mutants for infection of nondividing cells. J Virol, 82(24), 12001-8, 2008

Song, C, Aiken, C. Analysis of Human Cell Heterokaryons Demonstrates that Target Cell Restriction of Cyclosporin A-Resistant HIV-1 Mutants is Genetically Dominant. J Virol, 2007

Jiang, J, Aiken, C. Maturation-Dependent HIV-1 Particle Fusion Requires a Carboxyl-Terminal Region of the gp41 Cytoplasmic Tail. J Virol, 81, 9999-10008, 2007

Schneidewind, A, Brockman, MA, Yang, R, Adam, RI, Li, B, Le Gall, S, Rinaldo, CR, Craggs, SL, Allgaier, RL, Power, KA, Kuntzen, T, Tung, CS, LaBute, MX, Mueller, SM, Harrer, T, McMichael, AJ, Goulder, PJ, Aiken, C, Brander, C, Kelleher, AD, Allen, TM. Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in Gag is associated with a dramatic reduction in human immunodeficiency virus type 1 replication. J Virol, 81(22), 12382-93, 2007

Pion, M, Arrighi, JF, Jiang, J, Lundquist, CA, Hartley, O, Aiken, C, Piguet, V. Analysis of HIV-1-X4 fusion with immature dendritic cells identifies a specific restriction that is independent of CXCR4 levels. J Invest Dermatol, 127(2), 319-23, 2007

Yang, R, Aiken, C. A mutation in alpha helix 3 of CA renders human immunodeficiency virus type 1 cyclosporin A resistant and dependent: rescue by a second-site substitution in a distal region of CA. J Virol, 81(8), 3749-56, 2007

Qi, M, Aiken, C. Selective restriction of Nef-defective human immunodeficiency virus type 1 by a proteasome-dependent mechanism. J Virol, 81(3), 1534-6, 2007

Aiken, C. Viral and cellular factors that regulate HIV-1 uncoating. Curr Opin HIV AIDS, 1(3), 194-9, 2006

Zhou, J, Chen, CH, Aiken, C. Human immunodeficiency virus type 1 resistance to the small molecule maturation inhibitor 3-O-(3',3'-dimethylsuccinyl)-betulinic acid is conferred by a variety of single amino acid substitutions at the CA-SP1 cleavage site in Gag. J Virol, 80(24), 12095-101, 2006

Dismuke, DJ, Aiken, C. Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex. J Virol, 80(8), 3712-20, 2006

Davis, MR, Jiang, J, Zhou, J, Freed, EO, Aiken, C. A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41. J Virol, 80(5), 2405-17, 2006

Shi, J, Aiken, C. Saturation of TRIM5 alpha-mediated restriction of HIV-1 infection depends on the stability of the incoming viral capsid. Virology, 350(2), 493-500, 2006

Jiang, J, Aiken, C. Maturation of the viral core enhances the fusion of HIV-1 particles with primary human T cells and monocyte-derived macrophages. Virology, 2005

Zhou, J, Huang, L, Hachey, DL, Chen, CH, Aiken, C. Inhibition of HIV-1 maturation via drug association with the viral Gag protein in immature HIV-1 particles. J Biol Chem, 280(51), 42149-55, 2005

VanCompernolle, SE, Taylor, RJ, Oswald-Richter, K, Jiang, J, Youree, BE, Bowie, JH, Tyler, MJ, Conlon, JM, Wade, D, Aiken, C, Dermody, TS, KewalRamani, VN, Rollins-Smith, LA, Unutmaz, D. Antimicrobial peptides from amphibian skin potently inhibit human immunodeficiency virus infection and transfer of virus from dendritic cells to T cells. J Virol, 79(18), 11598-606, 2005

Aiken, C, Chen, CH. Betulinic acid derivatives as HIV-1 antivirals. Trends Mol Med, 11(1), 31-6, 2005

Forshey, BM, Shi, J, Aiken, C. Structural requirements for recognition of the human immunodeficiency virus type 1 core during host restriction in owl monkey cells. J Virol, 79(2), 869-75, 2005

Lundquist, Christopher A, Zhou, Jing, Aiken, Christopher. Nef stimulates human immunodeficiency virus type 1 replication in primary T cells by enhancing virion-associated gp120 levels: coreceptor-dependent requirement for Nef in viral replication. J Virol, 78(12), 6287-96, 2004

Zhou, Jing, Chen, Chin, Aiken, Christopher. The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3'',3''-dimethylsuccinyl}-betulinic acid. Retrovirology, 1(1), 15, 2004

Zhou, Jing, Yuan, Xiong, Dismuke, David, Forshey, Brett M, Lundquist, Christopher, Lee, Kuo-Hsiung, Aiken, Christopher, Chen, Chin Ho. Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation. J Virol, 78(2), 922-9, 2004

Wyma, Donald J, Jiang, Jiyang, Shi, Jiong, Zhou, Jing, Lineberger, Janet E, Miller, Michael D, Aiken, Christopher. Coupling of human immunodeficiency virus type 1 fusion to virion maturation: a novel role of the gp41 cytoplasmic tail. J Virol, 78(7), 3429-35, 2004

Huang, L. , Yuan, X., Aiken, C., and Chen, C. H.. Bifunctional anti-HIV-1 small molecules with two novel mechanisms of action. Antimicrobial Agents and Chemotherapy , 48, 663-665, 2004

Ganser, B.K., von Schwedler, U.K., Stray, K.M., Aiken, C., and Sundquist, W.I.. Assembly Properties of the HIV-1 CA Protein. J. Virol., 78, 2545-2552, 2004

Forshey, Brett M, Aiken, Christopher. Disassembly of human immunodeficiency virus type 1 cores in vitro reveals association of Nef with the subviral ribonucleoprotein complex. J Virol, 77(7), 4409-14, 2003

Tobiume, Minoru, Lineberger, Janet E, Lundquist, Christopher A, Miller, Michael D, Aiken, Christopher. Nef does not affect the efficiency of human immunodeficiency virus type 1 fusion with target cells. J Virol, 77(19), 10645-50, 2003

Lundquist, Christopher A, Tobiume, Minoru, Zhou, Jing, Unutmaz, Derya, Aiken, Christopher. Nef-mediated downregulation of CD4 enhances human immunodeficiency virus type 1 replication in primary T lymphocytes. J Virol, 76(9), 4625-33, 2002

Forshey, Brett M, von Schwedler, Uta, Sundquist, Wesley I, Aiken, Christopher. Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication. J Virol, 76(11), 5667-77, 2002

Zhou, J, Aiken, C. Nef enhances human immunodeficiency virus type 1 infectivity resulting from intervirion fusion: evidence supporting a role for Nef at the virion envelope. J Virol, 75(13), 5851-9, 2001

Chazal, N., Singer, G., Aiken, C., Hammarskjold, M.L., and Rekosh, D. HIV-1 particles pseudotyped with envelope proteins that fuse at low pH no longer require Nef for optimal infectivity. J. Virol., 75, 4014-4018, 2001

Wyma, D J, Kotov, A, Aiken, C. Evidence for a stable interaction of gp41 with Pr55(Gag) in immature human immunodeficiency virus type 1 particles. J Virol, 74(20), 9381-7, 2000

Kotov, A, Zhou, J, Flicker, P, Aiken, C. Association of Nef with the human immunodeficiency virus type 1 core. J Virol, 73(10), 8824-30, 1999

Aiken, C. Mechanistic independence of Nef and cyclophilin A enhancement of human immunodeficiency virus type 1 infectivity. Virology, 248(1), 139-47, 1998

Mangasarian, A., Foti, M., Aiken, C., Chin, D., Carpentier, J.-L., and Trono, D. The HIV-1 Nef Protein Acts as a Connector with Sorting Pathways in the Golgi and at the Plasma Membrane. Immunity , 6, 67-77, 1997

Aiken, C. Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A. J Virol, 71(8), 5871-7, 1997

Foti, M., Carpentier, J.L., Aiken, C., Trono, D., Lew, D. P., Krause, K. H. Second-messenger regulation of receptor association with clathrin-coated pits: a novel and selective mechanism in the control of CD4 endocytosis. Molecular Biology of the Cell, 8, 1377-1389, 1997

Aiken, C., Krause, L., Chen, Y.-L., and Trono, D. Mutational analysis of HIV-1 Nef: identification of two mutants that are temperature- sensitive for CD4 downregulation. Virology , 217, 293-300, 1996

Koval, V., Jault, F. M., Pal, P. G., Moreno, T. N., Aiken, C., Trono, D.,Spector, S. A., and Spector, D. H. Differential Effects of Human Cytomegalovirus on Integrated and Unintegrated Human Immunodeficiency Virus Sequences. J. Virol., 69, 1645-1651, 1995

Aiken, C., and Trono, D. Nef stimulates human immunodeficiency virus type 1 proviral DNA synthesis. J. Virol. , 69, 5048-5056, 1995

Gallay, P., Swingler, S., Aiken, C., and Trono, D. HIV-1 Infection of Non-dividing Cells: C-terminal Tyrosine Phosphorylation of the Viral Matrix Protein is a Key Regulator. Cell, 80, 379-388, 1995

Aiken, C., Konner, J., Landau, N. R., Lenburg, M. E., and Trono, D. Nef Induces CD4 Endocytosis: Requirement for a Critical Dileucine Motif in the Membrane-Proximal CD4 Cytoplasmic Domain. Cell, 76, 853-864, 1994

Von Schwedler, U., Song, J., Aiken, C., and Trono, D. Vif is crucial for HIV-1 proviral DNA synthesis in infected cells. J. Virol., 67, 4945-4955, 1993

Aiken, C.R., McLaughlin, L.W., and Gumport, R.I. The Highly Homologous Isoschizomers RsrI Endonuclease and EcoRI Endonuclease Do Not Recognize Their Target Sequence Identically. J. Biol. Chem., 266, 19070-19078, 1991

Aiken, C. and Gumport, R.I. Base Analogues and Their Use in Studying Protein-DNA Interactions. Methods Enzymol, 208, 433-457, 1991

Aiken, C.R., Fisher, E.W., and Gumport, R.I. The Specific Binding, Bending and Unwinding of DNA by RsrI Endonuclease, and Isoschizomer of EcoRI. J. Biol. Chem., 266, 19063-19069, 1991

Kaszubska, W., Aiken, C.R., and Gumport, R.I. RsrI restriction-modification enzymes from Rhodobacter spaeroides. Gene , 74, 83-84, 1988

Aiken, C. and Gumport, R.I. Restriction endonuclease RsrI from Rhodobacter sphaeroides, an isoschizomer of EcoRI: purification and properties. Nucleic Acids Res., 16, 7901-7916, 1988