Christopher Aiken
Last active: 2/4/2016

Profile

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

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. HIV: Antiviral action countered by Nef. Aiken C (2015) Nature 526(7572): 202-3
    › Primary publication · 26416750 (PubMed)
  2. HIV-1 Resistance to the Capsid-Targeting Inhibitor PF74 Results in Altered Dependence on Host Factors Required for Virus Nuclear Entry. Zhou J, Price AJ, Halambage UD, James LC, Aiken C (2015) J Virol 89(17): 9068-79
    › Primary publication · 26109731 (PubMed) · PMC4524096 (PubMed Central)
  3. Microplate-based assay for identifying small molecules that bind a specific intersubunit interface within the assembled HIV-1 capsid. Halambage UD, Wong JP, Melancon BJ, Lindsley CW, Aiken C (2015) Antimicrob Agents Chemother 59(9): 5190-5
    › Primary publication · 26077250 (PubMed) · PMC4538492 (PubMed Central)
  4. Compensatory substitutions in the HIV-1 capsid reduce the fitness cost associated with resistance to a capsid-targeting small-molecule inhibitor. Shi J, Zhou J, Halambage UD, Shah VB, Burse MJ, Wu H, Blair WS, Butler SL, Aiken C (2015) J Virol 89(1): 208-19
    › Primary publication · 25320302 (PubMed) · PMC4301104 (PubMed Central)
  5. Structural insight into HIV-1 restriction by MxB. Fribourgh JL, Nguyen HC, Matreyek KA, Alvarez FJ, Summers BJ, Dewdney TG, Aiken C, Zhang P, Engelman A, Xiong Y (2014) Cell Host Microbe 16(5): 627-38
    › Primary publication · 25312384 (PubMed) · PMC4252739 (PubMed Central)
  6. Gene expression analysis of a panel of cell lines that differentially restrict HIV-1 CA mutants infection in a cyclophilin a-dependent manner. Shah VB, Aiken C (2014) PLoS One 9(3): e92724
    › Primary publication · 24663101 (PubMed) · PMC3963944 (PubMed Central)
  7. HIV-1 uncoating: connection to nuclear entry and regulation by host proteins. Ambrose Z, Aiken C (2014) Virology : 371-9
    › Primary publication · 24559861 (PubMed) · PMC3988234 (PubMed Central)
  8. In vivo functions of CPSF6 for HIV-1 as revealed by HIV-1 capsid evolution in HLA-B27-positive subjects. Henning MS, Dubose BN, Burse MJ, Aiken C, Yamashita M (2014) PLoS Pathog 10(1): e1003868
    › Primary publication · 24415937 (PubMed) · PMC3887095 (PubMed Central)
  9. Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Xu H, Franks T, Gibson G, Huber K, Rahm N, Strambio De Castillia C, Luban J, Aiken C, Watkins S, Sluis-Cremer N, Ambrose Z (2013) Retrovirology : 70
    › Primary publication · 23835323 (PubMed) · PMC3716918 (PubMed Central)
  10. Discovery of novel small-molecule HIV-1 replication inhibitors that stabilize capsid complexes. Lamorte L, Titolo S, Lemke CT, Goudreau N, Mercier JF, Wardrop E, Shah VB, von Schwedler UK, Langelier C, Banik SS, Aiken C, Sundquist WI, Mason SW (2013) Antimicrob Agents Chemother 57(10): 4622-31
    › Primary publication · 23817385 (PubMed) · PMC3811413 (PubMed Central)
  11. INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Mathew S, Nguyen M, Wu X, Pal A, Shah VB, Prasad VR, Aiken C, Kalpana GV (2013) Retrovirology : 66
    › Primary publication · 23799881 (PubMed) · PMC3708822 (PubMed Central)
  12. Retrovirus restriction by TRIM5 proteins requires recognition of only a small fraction of viral capsid subunits. Shi J, Friedman DB, Aiken C (2013) J Virol 87(16): 9271-8
    › Primary publication · 23785198 (PubMed) · PMC3754041 (PubMed Central)
  13. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P (2013) Nature 497(7451): 643-6
    › Primary publication · 23719463 (PubMed) · PMC3729984 (PubMed Central)
  14. The NTD-CTD intersubunit interface plays a critical role in assembly and stabilization of the HIV-1 capsid. Yufenyuy EL, Aiken C (2013) Retrovirology : 29
    › Primary publication · 23497318 (PubMed) · PMC3623829 (PubMed Central)
  15. The host proteins transportin SR2/TNPO3 and cyclophilin A exert opposing effects on HIV-1 uncoating. Shah VB, Shi J, Hout DR, Oztop I, Krishnan L, Ahn J, Shotwell MS, Engelman A, Aiken C (2013) J Virol 87(1): 422-32
    › Primary publication · 23097435 (PubMed) · PMC3536424 (PubMed Central)
  16. Structural insight into HIV-1 capsid recognition by rhesus TRIM5α. Yang H, Ji X, Zhao G, Ning J, Zhao Q, Aiken C, Gronenborn AM, Zhang P, Xiong Y (2012) Proc Natl Acad Sci U S A 109(45): 18372-7
    › Primary publication · 23091002 (PubMed) · PMC3494900 (PubMed Central)
  17. Unclosed HIV-1 capsids suggest a curled sheet model of assembly. Yu Z, Dobro MJ, Woodward CL, Levandovsky A, Danielson CM, Sandrin V, Shi J, Aiken C, Zandi R, Hope TJ, Jensen GJ (2013) J Mol Biol 425(1): 112-23
    › Primary publication · 23079241 (PubMed) · PMC3597093 (PubMed Central)
  18. Protease cleavage leads to formation of mature trimer interface in HIV-1 capsid. Meng X, Zhao G, Yufenyuy E, Ke D, Ning J, Delucia M, Ahn J, Gronenborn AM, Aiken C, Zhang P (2012) PLoS Pathog 8(8): e1002886
    › Primary publication · 22927821 (PubMed) · PMC3426514 (PubMed Central)
  19. Structural insights into the anti-HIV activity of the Oscillatoria agardhii agglutinin homolog lectin family. Koharudin LM, Kollipara S, Aiken C, Gronenborn AM (2012) J Biol Chem 287(40): 33796-811
    › Primary publication · 22865886 (PubMed) · PMC3460475 (PubMed Central)
  20. Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Yang R, Shi J, Byeon IJ, Ahn J, Sheehan JH, Meiler J, Gronenborn AM, Aiken C (2012) Retrovirology : 30
    › Primary publication · 22515365 (PubMed) · PMC3351742 (PubMed Central)
  21. In vitro uncoating of HIV-1 cores. Shah VB, Aiken C (2011) J Vis Exp (57)
    › Primary publication · 22105356 (PubMed) · PMC3308611 (PubMed Central)
  22. HIV Nuclear Entry: Clearing the Fog. Shah VB, Aiken C (2010) Viruses 2(5): 1190-4
    › Primary publication · 21994675 (PubMed) · PMC3187605 (PubMed Central)
  23. Maturation-induced cloaking of neutralization epitopes on HIV-1 particles. Joyner AS, Willis JR, Crowe JE, Aiken C (2011) PLoS Pathog 7(9): e1002234
    › Primary publication · 21931551 (PubMed) · PMC3169560 (PubMed Central)
  24. Immunology: TRIM5 does double duty. Aiken C, Joyce S (2011) Nature 472(7343): 305-6
    › Primary publication · 21512569 (PubMed)
  25. Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces. Zhao G, Ke D, Vu T, Ahn J, Shah VB, Yang R, Aiken C, Charlton LM, Gronenborn AM, Zhang P (2011) PLoS Pathog 7(3): e1002009
    › Primary publication · 21455494 (PubMed) · PMC3063768 (PubMed Central)
  26. Structure of the HIV-1 full-length capsid protein in a conformationally trapped unassembled state induced by small-molecule binding. Du S, Betts L, Yang R, Shi H, Concel J, Ahn J, Aiken C, Zhang P, Yeh JI (2011) J Mol Biol 406(3): 371-86
    › Primary publication · 21146540 (PubMed) · PMC3194004 (PubMed Central)
  27. Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization. Shi J, Zhou J, Shah VB, Aiken C, Whitby K (2011) J Virol 85(1): 542-9
    › Primary publication · 20962083 (PubMed) · PMC3014163 (PubMed Central)
  28. TRIM5alpha disrupts the structure of assembled HIV-1 capsid complexes in vitro. Black LR, Aiken C (2010) J Virol 84(13): 6564-9
    › Primary publication · 20410272 (PubMed) · PMC2903270 (PubMed Central)
  29. Structural convergence between Cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function. Byeon IJ, Meng X, Jung J, Zhao G, Yang R, Ahn J, Shi J, Concel J, Aiken C, Zhang P, Gronenborn AM (2009) Cell 139(4): 780-90
    › Primary publication · 19914170 (PubMed) · PMC2782912 (PubMed Central)
  30. Viral and cellular factors that regulate HIV-1 uncoating. Aiken C (2006) Curr Opin HIV AIDS 1(3): 194-9
    › Primary publication · 19372808 (PubMed)
  31. Cell-free assays for HIV-1 uncoating. Aiken C (2009) Methods Mol Biol : 41-53
    › Primary publication · 19020817 (PubMed) · PMC3842014 (PubMed Central)
  32. Cyclophilin A-dependent restriction of human immunodeficiency virus type 1 capsid mutants for infection of nondividing cells. Qi M, Yang R, Aiken C (2008) J Virol 82(24): 12001-8
    › Primary publication · 18829762 (PubMed) · PMC2593355 (PubMed Central)
  33. Biochemical characterization of a recombinant TRIM5alpha protein that restricts human immunodeficiency virus type 1 replication. Langelier CR, Sandrin V, Eckert DM, Christensen DE, Chandrasekaran V, Alam SL, Aiken C, Olsen JC, Kar AK, Sodroski JG, Sundquist WI (2008) J Virol 82(23): 11682-94
    › Primary publication · 18799573 (PubMed) · PMC2583683 (PubMed Central)
  34. Proteasomal degradation of TRIM5alpha during retrovirus restriction. Rold CJ, Aiken C (2008) PLoS Pathog 4(5): e1000074
    › Primary publication · 18497858 (PubMed) · PMC2374908 (PubMed Central)
  35. Nef enhances HIV-1 infectivity via association with the virus assembly complex. Qi M, Aiken C (2008) Virology 373(2): 287-97
    › Primary publication · 18191978 (PubMed) · PMC2440657 (PubMed Central)
  36. 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. 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 (2007) J Virol 81(22): 12382-93
    › Primary publication · 17804494 (PubMed) · PMC2169010 (PubMed Central)
  37. Analysis of human cell heterokaryons demonstrates that target cell restriction of cyclosporine-resistant human immunodeficiency virus type 1 mutants is genetically dominant. Song C, Aiken C (2007) J Virol 81(21): 11946-56
    › Primary publication · 17715216 (PubMed) · PMC2168785 (PubMed Central)
  38. Maturation-dependent human immunodeficiency virus type 1 particle fusion requires a carboxyl-terminal region of the gp41 cytoplasmic tail. Jiang J, Aiken C (2007) J Virol 81(18): 9999-10008
    › Primary publication · 17609279 (PubMed) · PMC2045384 (PubMed Central)
  39. 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. Yang R, Aiken C (2007) J Virol 81(8): 3749-56
    › Primary publication · 17267487 (PubMed) · PMC1866112 (PubMed Central)
  40. Selective restriction of Nef-defective human immunodeficiency virus type 1 by a proteasome-dependent mechanism. Qi M, Aiken C (2007) J Virol 81(3): 1534-6
    › Primary publication · 17108041 (PubMed) · PMC1797497 (PubMed Central)
  41. 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. Zhou J, Chen CH, Aiken C (2006) J Virol 80(24): 12095-101
    › Primary publication · 17035324 (PubMed) · PMC1676313 (PubMed Central)
  42. Analysis of HIV-1-X4 fusion with immature dendritic cells identifies a specific restriction that is independent of CXCR4 levels. Pion M, Arrighi JF, Jiang J, Lundquist CA, Hartley O, Aiken C, Piguet V (2007) J Invest Dermatol 127(2): 319-23
    › Primary publication · 16917492 (PubMed)
  43. Saturation of TRIM5 alpha-mediated restriction of HIV-1 infection depends on the stability of the incoming viral capsid. Shi J, Aiken C (2006) Virology 350(2): 493-500
    › Primary publication · 16624363 (PubMed)
  44. Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex. Dismuke DJ, Aiken C (2006) J Virol 80(8): 3712-20
    › Primary publication · 16571788 (PubMed) · PMC1440469 (PubMed Central)
  45. A mutation in the human immunodeficiency virus type 1 Gag protein destabilizes the interaction of the envelope protein subunits gp120 and gp41. Davis MR, Jiang J, Zhou J, Freed EO, Aiken C (2006) J Virol 80(5): 2405-17
    › Primary publication · 16474147 (PubMed) · PMC1395406 (PubMed Central)
  46. Maturation of the viral core enhances the fusion of HIV-1 particles with primary human T cells and monocyte-derived macrophages. Jiang J, Aiken C (2006) Virology 346(2): 460-8
    › Primary publication · 16375941 (PubMed)
  47. Inhibition of HIV-1 maturation via drug association with the viral Gag protein in immature HIV-1 particles. Zhou J, Huang L, Hachey DL, Chen CH, Aiken C (2005) J Biol Chem 280(51): 42149-55
    › Primary publication · 16251182 (PubMed)
  48. Antimicrobial peptides from amphibian skin potently inhibit human immunodeficiency virus infection and transfer of virus from dendritic cells to T cells. 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 (2005) J Virol 79(18): 11598-606
    › Primary publication · 16140737 (PubMed) · PMC1212620 (PubMed Central)
  49. Betulinic acid derivatives as HIV-1 antivirals. Aiken C, Chen CH (2005) Trends Mol Med 11(1): 31-6
    › Primary publication · 15649820 (PubMed)
  50. Structural requirements for recognition of the human immunodeficiency virus type 1 core during host restriction in owl monkey cells. Forshey BM, Shi J, Aiken C (2005) J Virol 79(2): 869-75
    › Primary publication · 15613315 (PubMed) · PMC538572 (PubMed Central)
  51. 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. Zhou J, Chen CH, Aiken C (2004) Retrovirology : 15
    › Primary publication · 15225375 (PubMed) · PMC479704 (PubMed Central)
  52. 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. Lundquist CA, Zhou J, Aiken C (2004) J Virol 78(12): 6287-96
    › Primary publication · 15163722 (PubMed) · PMC416500 (PubMed Central)
  53. Bifunctional anti-human immunodeficiency virus type 1 small molecules with two novel mechanisms of action. Huang L, Yuan X, Aiken C, Chen CH (2004) Antimicrob Agents Chemother 48(2): 663-5
    › Primary publication · 14742233 (PubMed) · PMC321552 (PubMed Central)
  54. Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation. Zhou J, Yuan X, Dismuke D, Forshey BM, Lundquist C, Lee KH, Aiken C, Chen CH (2004) J Virol 78(2): 922-9
    › Primary publication · 14694123 (PubMed) · PMC368845 (PubMed Central)
  55. Nef does not affect the efficiency of human immunodeficiency virus type 1 fusion with target cells. Tobiume M, Lineberger JE, Lundquist CA, Miller MD, Aiken C (2003) J Virol 77(19): 10645-50
    › Primary publication · 12970449 (PubMed) · PMC228506 (PubMed Central)
  56. Disassembly of human immunodeficiency virus type 1 cores in vitro reveals association of Nef with the subviral ribonucleoprotein complex. Forshey BM, Aiken C (2003) J Virol 77(7): 4409-14
    › Primary publication · 12634398 (PubMed) · PMC150647 (PubMed Central)
  57. Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication. Forshey BM, von Schwedler U, Sundquist WI, Aiken C (2002) J Virol 76(11): 5667-77
    › Primary publication · 11991995 (PubMed) · PMC137032 (PubMed Central)
  58. Nef-mediated downregulation of CD4 enhances human immunodeficiency virus type 1 replication in primary T lymphocytes. Lundquist CA, Tobiume M, Zhou J, Unutmaz D, Aiken C (2002) J Virol 76(9): 4625-33
    › Primary publication · 11932428 (PubMed) · PMC155097 (PubMed Central)
  59. Nef enhances human immunodeficiency virus type 1 infectivity resulting from intervirion fusion: evidence supporting a role for Nef at the virion envelope. Zhou J, Aiken C (2001) J Virol 75(13): 5851-9
    › Primary publication · 11390586 (PubMed) · PMC114300 (PubMed Central)
  60. Human immunodeficiency virus type 1 particles pseudotyped with envelope proteins that fuse at low pH no longer require Nef for optimal infectivity. Chazal N, Singer G, Aiken C, Hammarskjöld ML, Rekosh D (2001) J Virol 75(8): 4014-8
    › Primary publication · 11264394 (PubMed) · PMC114896 (PubMed Central)
  61. Evidence for a stable interaction of gp41 with Pr55(Gag) in immature human immunodeficiency virus type 1 particles. Wyma DJ, Kotov A, Aiken C (2000) J Virol 74(20): 9381-7
    › Primary publication · 11000206 (PubMed) · PMC112366 (PubMed Central)
  62. Association of Nef with the human immunodeficiency virus type 1 core. Kotov A, Zhou J, Flicker P, Aiken C (1999) J Virol 73(10): 8824-30
    › Primary publication · 10482638 (PubMed) · PMC112905 (PubMed Central)
  63. Mechanistic independence of Nef and cyclophilin A enhancement of human immunodeficiency virus type 1 infectivity. Aiken C (1998) Virology 248(1): 139-47
    › Primary publication · 9705263 (PubMed) · PMC3937310 (PubMed Central)
  64. Second-messenger regulation of receptor association with clathrin-coated pits: a novel and selective mechanism in the control of CD4 endocytosis. Foti M, Carpentier JL, Aiken C, Trono D, Lew DP, Krause KH (1997) Mol Biol Cell 8(7): 1377-89
    › Primary publication · 9243514 (PubMed) · PMC276159 (PubMed Central)
  65. 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. Aiken C (1997) J Virol 71(8): 5871-7
    › Primary publication · 9223476 (PubMed) · PMC191842 (PubMed Central)
  66. The HIV-1 Nef protein acts as a connector with sorting pathways in the Golgi and at the plasma membrane. Mangasarian A, Foti M, Aiken C, Chin D, Carpentier JL, Trono D (1997) Immunity 6(1): 67-77
    › Primary publication · 9052838 (PubMed)
  67. Mutational analysis of HIV-1 Nef: identification of two mutants that are temperature-sensitive for CD4 downregulation. Aiken C, Krause L, Chen YL, Trono D (1996) Virology 217(1): 293-300
    › Primary publication · 8599214 (PubMed)