HIV-1 capsid: the multifaceted key player in HIV-1 infection (original) (raw)

• Briggs, J. A. et al. The stoichiometry of Gag protein in HIV-1. Nat. Struct. Mol. Biol. 11, 672–675 (2004).
  Article CAS PubMed Google Scholar
• Ganser, B. K., Li, S., Klishko, V. Y., Finch, J. T. & Sundquist, W. I. Assembly and analysis of conical models for the HIV-1 core. Science 283, 80–83 (1999). This paper established the first molecular models to explain the fullerene-cone structure of the HIV-1 core.
  Article CAS PubMed Google Scholar
• Li, S., Hill, C. P., Sundquist, W. I. & Finch, J. T. Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407, 409–413 (2000).
  Article CAS PubMed Google Scholar
• Ganser-Pornillos, B. K., Cheng, A. & Yeager, M. Structure of full-length HIV-1 CA: a model for the mature capsid lattice. Cell 131, 70–79 (2007).The first high-resolution structure of assembled HIV-1 CA, identifying critical interfaces that promote capsid assembly and stability.
  Article CAS PubMed Google Scholar
• Byeon, I. J. et al. Structural convergence between Cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function. Cell 139, 780–790 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Zhao, G. et al. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497, 643–646 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Bhattacharya, A. et al. Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. Proc. Natl Acad. Sci. USA 111, 18625–18630 (2014).
  Article CAS PubMed Google Scholar
• Price, A. J. et al. Host cofactors and pharmacologic ligands share an essential interface in HIV-1 capsid that is lost upon disassembly. PLoS Pathog. 10, e1004459 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Accola, M. A., Öhagen, A. & Göttlinger, H. G. Isolation of human immunodeficiency virus type 1 cores: retention of Vpr in the absence of p6_gag_. J. Virol. 74, 6198–6202 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Kotov, A., Zhou, J., Flicker, P. & Aiken, C. Association of Nef with the human immunodeficiency virus type 1 core. J. Virol. 73, 8824–8830 (1999).
  CAS PubMed PubMed Central Google Scholar
• Welker, R., Hohenberg, H., Tessmer, U., Huckhagel, C. & Kräusslich, H. G. Biochemical and structural analysis of isolated mature cores of human immunodeficiency virus type 1. J. Virol. 74, 1168–1177 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Forshey, B. M., von Schwedler, U., Sundquist, W. I. & Aiken, C. Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication. J. Virol. 76, 5667–5677 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Gao, D. et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science 341, 903–906 (2013).
  Article CAS PubMed Google Scholar
• Lahaye, X. et al. The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells. Immunity 39, 1132–1142 (2013).
  Article CAS PubMed Google Scholar
• Rasaiyaah, J. et al. HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature 503, 402–405 (2013). References 14 and 15 demonstrate the substantial consequences associated with slight changes in viral CA and its ability to interact with specific cellular factors during infection. Reference 15 additionally provides insight into how certain CA mutations induce IFN responses in primary cells, perhaps explaining the strong selective pressure operating against these mutations in vivo . The paper also demonstrates that interference with uncoating or engagement of certain cellular factors can induce a potent innate immune response.
  Article CAS PubMed PubMed Central Google Scholar
• Yan, N., Regalado-Magdos, A. D., Stiggelbout, B., Lee-Kirsch, M. A. & Lieberman, J. The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. Nat. Immunol. 11, 1005–1013 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Aiken, C. Viral and cellular factors that regulate HIV-1 uncoating. Curr. Opin. HIV AIDS 1, 194–199 (2006).
  Article PubMed Google Scholar
• Yamashita, M. & Emerman, M. Capsid is a dominant determinant of retrovirus infectivity in nondividing cells. J. Virol. 78, 5670–5678 (2004). This paper showed that CA is the viral protein underlying the ability of HIV-1 to infect non-dividing cells.
  Article CAS PubMed PubMed Central Google Scholar
• Yamashita, M., Perez, O., Hope, T. J. & Emerman, M. Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells. PLoS Pathog. 3, 1502–1510 (2007).
  Article CAS PubMed Google Scholar
• Zhou, L. et al. Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. PLoS Pathog. 7, e1002194 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Matreyek, K. A. & Engelman, A. The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsid. J. Virol. 85, 7818–7827 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Matreyek, K. A., Yucel, S. S., Li, X. & Engelman, A. Nucleoporin NUP153 phenylalanine-glycine motifs engage a common binding pocket within the HIV-1 capsid protein to mediate lentiviral infectivity. PLoS Pathog. 9, e1003693 (2013). This paper describes molecular mapping of the NUP153–CA interface; results that were ultimately confirmed by structural studies.
  Article CAS PubMed PubMed Central Google Scholar
• Peng, K. et al. Quantitative microscopy of functional HIV post-entry complexes reveals association of replication with the viral capsid. eLife 3, e04114 (2014).
  Article PubMed PubMed Central Google Scholar
• Hulme, A. E., Kelley, Z., Foley, D. & Hope, T. J. Complementary assays reveal a low level of CA associated with viral complexes in the nuclei of HIV-1-infected cells. J. Virol. 5350–5361 (2015).
• Lowe, A. R. et al. Selectivity mechanism of the nuclear pore complex characterized by single cargo tracking. Nature 467, 600–603 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Pante, N. & Kann, M. Nuclear pore complex is able to transport macromolecules with diameters of about 39 nm. Mol. Biol. Cell 13, 425–434 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Yang, R. et al. Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects. Retrovirology 9, 30 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Rihn, S. J. et al. Extreme genetic fragility of the HIV-1 capsid. PLoS Pathog. 9, e1003461 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Jia, X., Zhao, Q. & Xiong, Y. HIV suppression by host restriction factors and viral immune evasion. Curr. Opin. Struct. Biol. 31, 106–114 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Mortuza, G. B. et al. High-resolution structure of a retroviral capsid hexameric amino-terminal domain. Nature 431, 481–485 (2004).
  Article CAS PubMed Google Scholar
• Pornillos, O. et al. X-ray structures of the hexameric building block of the HIV capsid. Cell 137, 1282–1292 (2009).
  Article PubMed PubMed Central Google Scholar
• Di Nunzio, F. et al. Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication. Virology 440, 8–18 (2013).
  Article CAS PubMed Google Scholar
• Koh, Y. et al. Differential effects of human immunodeficiency virus type 1 capsid and cellular factors nucleoporin 153 and LEDGF/p75 on the efficiency and specificity of viral DNA integration. J. Virol. 87, 648–658 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Ocwieja, K. E. et al. HIV integration targeting: a pathway involving transportin-3 and the nuclear pore protein RanBP2. PLoS Pathog. 7, e1001313 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Fassati, A. & Goff, S. P. Characterization of intracellular reverse transcription complexes of human immunodeficiency virus type 1. J. Virol. 75, 3626–3635 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Miller, M. D., Farnet, C. M. & Bushman, F. D. Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition. J. Virol. 71, 5382–5390 (1997).
  CAS PubMed PubMed Central Google Scholar
• Fassati, A. & Goff, S. P. Characterization of intracellular reverse transcription complexes of Moloney murine leukemia virus. J. Virol. 73, 8919–8925 (1999).
  CAS PubMed PubMed Central Google Scholar
• Hulme, A. E., Perez, O. & Hope, T. J. Complementary assays reveal a relationship between HIV-1 uncoating and reverse transcription. Proc. Natl Acad. Sci. USA 108, 9975–9980 (2011).
  Article CAS PubMed Google Scholar
• Lukic, Z., Dharan, A., Fricke, T., Diaz-Griffero, F. & Campbell, E. M. HIV-1 uncoating is facilitated by dynein and kinesin-1. J. Virol. 88, 13613–13625 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Perez-Caballero, D., Hatziioannou, T., Zhang, F., Cowan, S. & Bieniasz, P. D. Restriction of human immunodeficiency virus type 1 by TRIM-CypA occurs with rapid kinetics and independently of cytoplasmic bodies, ubiquitin, and proteasome cctivity. J. Virol. 79, 15567–15572 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• McDonald, D. et al. Visualization of the intracellular behavior of HIV in living cells. J. Cell Biol. 159, 441–452 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Xu, H. et al. Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Retrovirology 10, 70 (2013).
  Article PubMed PubMed Central Google Scholar
• Butler, S. L., Hansen, M. S. & Bushman, F. D. A quantitative assay for HIV DNA integration in vivo. Nat. Med. 7, 631–634 (2001).
  Article CAS PubMed Google Scholar
• Arhel, N. J. et al. HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore. EMBO J. 26, 3025–3037 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Farnet, C. M. & Bushman, F. D. HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of preintegration complexes in vitro. Cell 88, 483–492 (1997).
  Article CAS PubMed Google Scholar
• Li, L. et al. Retroviral cDNA integration: stimulation by HMG I family proteins. J. Virol. 74, 10965–10974 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Hilditch, L. & Towers, G. J. A model for cofactor use during HIV-1 reverse transcription and nuclear entry. Curr. Opin. Virol. 4, 32–36 (2014). This paper provides a noteworthy model of CA cofactor engagement not entirely described in this Review.
  Article CAS PubMed PubMed Central Google Scholar
• Briones, M. S., Dobard, C. W. & Chow, S. A. Role of human immunodeficiency virus type 1 integrase in uncoating of the viral core. J. Virol. 84, 5181–5190 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Jurado, K. A. et al. Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation. Proc. Natl Acad. Sci. USA 110, 8690–8695 (2013).
  Article CAS PubMed Google Scholar
• Engelman, A., Englund, G., Orenstein, J. M., Martin, M. A. & Craigie, R. Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. J. Virol. 69, 2729–2736 (1995).
  CAS PubMed PubMed Central Google Scholar
• Yang, Y., Fricke, T. & Diaz-Griffero, F. Inhibition of reverse transcriptase activity increases stability of the HIV-1 core. J. Virol. 87, 683–687 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Zhu, K., Dobard, C. & Chow, S. A. Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. J. Virol. 78, 5045–5055 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Franke, E. K., Yuan, H. E. & Luban, J. Specific incorporation of cyclophilin A into HIV-1 virions. Nature 372, 359–362 (1994).
  Article CAS PubMed Google Scholar
• Luban, J., Bossolt, K. L., Franke, E. K., Kalpana, G. V. & Goff, S. P. Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B. Cell 73, 1067–1078 (1993).
  Article CAS PubMed Google Scholar
• Thali, M. et al. Functional association of cyclophilin A with HIV-1 virions. Nature 372, 363–365 (1994).
  Article CAS PubMed Google Scholar
• Hatziioannou, T., Perez-Caballero, D., Cowan, S. & Bieniasz, P. D. Cyclophilin interactions with incoming human immunodeficiency virus type 1 capsids with opposing effects on infectivity in human cells. J. Virol. 79, 176–183 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Sokolskaja, E., Sayah, D. M. & Luban, J. Target cell cyclophilin A modulates human immunodeficiency virus type 1 infectivity. J. Virol. 78, 12800–12808 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Kootstra, N. A., Munk, C., Tonnu, N., Landau, N. R. & Verma, I. M. Abrogation of postentry restriction of HIV-1-based lentiviral vector transduction in simian cells. Proc. Natl Acad. Sci. USA 100, 1298–1303 (2003).
  Article CAS PubMed Google Scholar
• Towers, G. J. et al. Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors. Nat. Med. 9, 1138–1143 (2003).
  Article CAS PubMed Google Scholar
• Gamble, T. R. et al. Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell 87, 1285–1294 (1996).
  Article CAS PubMed Google Scholar
• Braaten, D. et al. Cyclosporine A-resistant human immunodeficiency virus type 1 mutants demonstrate that Gag encodes the functional target of cyclophilin A. J. Virol. 70, 5170–5176 (1996).
  CAS PubMed PubMed Central Google Scholar
• Braaten, D., Franke, E. K. & Luban, J. Cyclophilin A is required for an early step in the life cycle of human immunodeficiency virus type 1 before the initiation of reverse transcription. J. Virol. 70, 3551–3560 (1996).
  CAS PubMed PubMed Central Google Scholar
• Braaten, D. & Luban, J. Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human T cells. EMBO J. 20, 1300–1309 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• De Iaco, A. & Luban, J. Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA. Retrovirology 11, 11 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Li, Y., Kar, A. K. & Sodroski, J. Target cell type-dependent modulation of human immunodeficiency virus type 1 capsid disassembly by cyclophilin A. J. Virol. 83, 10951–10962 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Bosco, D. A., Eisenmesser, E. Z., Pochapsky, S., Sundquist, W. I. & Kern, D. Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A. Proc. Natl Acad. Sci. USA 99, 5247–5252 (2002).
  Article CAS PubMed Google Scholar
• Fricke, T. et al. Human cytosolic extracts stabilize the HIV-1 core. J. Virol. 87, 10587–10597 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Shah, V. B. et al. The host proteins transportin SR2/TNPO3 and cyclophilin A exert opposing effects on HIV-1 uncoating. J. Virol. 87, 422–432 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Aberham, C., Weber, S. & Phares, W. Spontaneous mutations in the human immunodeficiency virus type 1 gag gene that affect viral replication in the presence of cyclosporins. J. Virol. 70, 3536–3544 (1996).
  CAS PubMed PubMed Central Google Scholar
• Schneidewind, A. et al. 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, 12382–12393 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• 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, 3749–3756 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• 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, 12001–12008 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Yin, L., Braaten, D. & Luban, J. Human immunodeficiency virus type 1 replication is modulated by host cyclophilin A expression levels. J. Virol. 72, 6430–6436 (1998).
  CAS PubMed PubMed Central Google Scholar
• Ylinen, L. M. et al. Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D. J. Virol. 83, 2044–2047 (2009).
  Article CAS PubMed Google Scholar
• Arhel, N. et al. Quantitative four-dimensional tracking of cytoplasmic and nuclear HIV-1 complexes. Nat. Methods 3, 817–824 (2006).
  Article CAS PubMed Google Scholar
• Sabo, Y. et al. HIV-1 induces the formation of stable microtubules to enhance early infection. Cell Host Microbe 14, 535–546 (2013).
  Article CAS PubMed Google Scholar
• Jayappa, K. D. et al. Human immunodeficiency virus type 1 employs the cellular dynein light chain 1 protein for reverse transcription through interaction with its integrase protein. J. Virol. 89, 3497–3511 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Pawlica, P. & Berthoux, L. Cytoplasmic dynein promotes HIV-1 uncoating. Viruses 6, 4195–4211 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Strunze, S. et al. Kinesin-1-mediated capsid disassembly and disruption of the nuclear pore complex promote virus infection. Cell Host Microbe 10, 210–223 (2011).
  Article CAS PubMed Google Scholar
• Yamashita, M. & Emerman, M. Retroviral infection of non-dividing cells: old and new perspectives. Virology 344, 88–93 (2006).
  Article CAS PubMed Google Scholar
• Brass, A. L. et al. Identification of host proteins required for HIV infection through a functional genomic screen. Science 319, 921–926 (2008).
  Article CAS PubMed Google Scholar
• Konig, R. et al. Global analysis of host–pathogen interactions that regulate early-stage HIV-1 replication. Cell 135, 49–60 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, K. et al. Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe 7, 221–233 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Zhou, H. et al. Genome-scale RNAi screen for host factors required for HIV replication. Cell Host Microbe 4, 495–504 (2008).
  Article CAS PubMed Google Scholar
• Ambrose, Z. & Aiken, C. HIV-1 uncoating: connection to nuclear entry and regulation by host proteins. Virology, 454–455, 371–379 (2014).
  Article CAS PubMed Google Scholar
• Price, A. J. et al. CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. PLoS Pathog. 8, e1002896 (2012). References 7, 8 and 86 demonstrate that some assembled CA must remain associated with the viral complex when it interacts with NUP153 and CPSF6.
  Article CAS PubMed PubMed Central Google Scholar
• Ruepp, M. D. et al. Mammalian pre-mRNA 3′ end processing factor CF Im 68 functions in mRNA export. Mol. Biol. Cell 20, 5211–5223 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Hori, T. et al. A carboxy-terminally truncated human CPSF6 lacking residues encoded by exon 6 inhibits HIV-1 cDNA synthesis and promotes capsid disassembly. J. Virol. 87, 7726–7736 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Henning, M. S., Dubose, B. N., Burse, M. J., 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, e1003868 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• De Iaco, A. et al. TNPO3 protects HIV-1 replication from CPSF6-mediated capsid stabilization in the host cell cytoplasm. Retrovirology 10, 20 (2013). An elegant molecular study establishing an assay to differentiate between 2-LTR circles and auto-integrants that is critical for understanding the roles of cellular factors and the stages in the lifecycle at which they act.
  Article CAS PubMed PubMed Central Google Scholar
• Lee, K. et al. HIV-1 capsid-targeting domain of cleavage and polyadenylation specificity factor 6. J. Virol. 86, 3851–3860 (2012). A seminal study identifying truncated CPSF6 as a dominant negative inhibitor of infection, leading both to the appreciation of the role of CPSF6 in HIV-1 infection and to the N74D mutant, which remains a critical tool in studies in this area.
  Article CAS PubMed PubMed Central Google Scholar
• Kataoka, N., Bachorik, J. L. & Dreyfuss, G. Transportin-SR, a nuclear import receptor for SR proteins. J. Cell Biol. 145, 1145–1152 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Christ, F. et al. Transportin-SR2 imports HIV into the nucleus. Curr. Biol. 18, 1192–1202 (2008).
  Article CAS PubMed Google Scholar
• Cribier, A. et al. Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Retrovirology 8, 104 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Krishnan, L. et al. The requirement for cellular transportin 3 (TNPO3 or TRN-SR2) during infection maps to human immunodeficiency virus type 1 capsid and not integrase. J. Virol. 84, 397–406 (2010).
  Article CAS PubMed Google Scholar
• De Houwer, S. et al. Identification of residues in the C-terminal domain of HIV-1 integrase that mediate binding to the transportin-SR2 protein. J. Biol. Chem. 287, 34059–34068 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• De Iaco, A. & Luban, J. Inhibition of HIV-1 infection by TNPO3 depletion is determined by capsid and detectable after viral cDNA enters the nucleus. Retrovirology 8, 98 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Valle-Casuso, J. C. et al. TNPO3 is required for HIV-1 replication after nuclear import but prior to integration and binds the HIV-1 core. J. Virol. 86, 5931–5936 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Schaller, T. et al. HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. PLoS Pathog. 7, e1002439 (2011). This paper demonstrates the connection between HIV-1 CA associations and integration-site selection when in the nucleus.
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, R., Mehla, R. & Chauhan, A. Perturbation of host nuclear membrane component RanBP2 impairs the nuclear import of human immunodeficiency virus-1 preintegration complex (DNA). PLoS ONE 5, e15620 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Labokha, A. A. & Fassati, A. Viruses challenge selectivity barrier of nuclear pores. Viruses 5, 2410–2423 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Strambio-De-Castillia, C., Niepel, M. & Rout, M. P. The nuclear pore complex: bridging nuclear transport and gene regulation. Nat. Rev. Mol. Cell Biol. 11, 490–501 (2010).
  Article CAS PubMed Google Scholar
• Di Nunzio, F. et al. Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration. PLoS ONE 7, e46037 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Meehan, A. M. et al. A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection. PLoS Pathog. 10, e1003969 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Bichel, K. et al. HIV-1 capsid undergoes coupled binding and isomerization by the nuclear pore protein NUP358. Retrovirology 10, 81 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Daigle, N. et al. Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells. J. Cell Biol. 154, 71–84 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Hirokawa, N., Noda, Y., Tanaka, Y. & Niwa, S. Kinesin superfamily motor proteins and intracellular transport. Nat. Rev. Mol. Cell Biol. 10, 682–696 (2009).
  Article CAS PubMed Google Scholar
• Hulme, A. E., Kelley, Z., Okocha, E. A. & Hope, T. J. Identification of capsid mutations that alter the rate of HIV-1 uncoating in infected cells. J. Virol. 89, 643–651 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Amie, S. M., Noble, E. & Kim, B. Intracellular nucleotide levels and the control of retroviral infections. Virology 436, 247–254 (2013).
  Article CAS PubMed Google Scholar
• Blair, W. S. et al. HIV capsid is a tractable target for small molecule therapeutic intervention. PLoS Pathog. 6, e1001220 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Shi, J., Zhou, J., Shah, V. B., Aiken, C. & Whitby, K. Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization. J. Virol. 85, 542–549 (2011).
  Article CAS PubMed Google Scholar
• Lamorte, L. et al. Discovery of novel small-molecule HIV-1 replication inhibitors that stabilize capsid complexes. Antimicrob. Agents Chemother. 57, 4622–4631 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Fricke, T., Buffone, C., Opp, S., Valle-Casuso, J. & Diaz-Griffero, F. BI-2 destabilizes HIV-1 cores during infection and prevents binding of CPSF6 to the HIV-1 capsid. Retrovirology 11, 120 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Azzoni, L. et al. Pegylated interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration. J. Infect. Dis. 207, 213–222 (2013).
  Article CAS PubMed Google Scholar
• Sandler, N. G. et al. Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 511, 601–605 (2014). This paper provides an elegant demonstration of the potential utility of IFN response in controlling infection, showing the correlation between IFN-stimulated gene expression and control of viral infection.
  Article CAS PubMed PubMed Central Google Scholar
• Bosinger, S. E. & Utay, N. S. Type I interferon: understanding its role in HIV pathogenesis and therapy. Curr. HIV/AIDS Rep. 12, 41–53 (2015).
  Article PubMed Google Scholar
• Doyle, T., Goujon, C. & Malim, M. H. HIV-1 and interferons: who's interfering with whom? Nat. Rev. Microbiol. 13, 403–413 (2015).
  Article CAS PubMed Google Scholar
• Siliciano, R. F. & Greene, W. C. HIV latency. Cold Spring Harb. Perspect. Med. 1, a007096 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Shah, V. B. & Aiken, C. In vitro uncoating of HIV-1 cores. J. Vis. Exp. 57, e3384 (2011).
  Google Scholar
• Stremlau, M. et al. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor. Proc. Natl Acad. Sci. USA 103, 5514–5519 (2006).
  Article CAS PubMed Google Scholar
• Kutluay, S. B., Perez-Caballero, D. & Bieniasz, P. D. Fates of retroviral core components during unrestricted and TRIM5-restricted infection. PLoS Pathog. 9, e1003214 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Fricke, T. et al. MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1. Retrovirology 11, 68 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Iordanskiy, S., Berro, R., Altieri, M., Kashanchi, F. & Bukrinsky, M. Intracytoplasmic maturation of the human immunodeficiency virus type 1 reverse transcription complexes determines their capacity to integrate into chromatin. Retrovirology 3, 4 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Burdick, R. C., Hu, W. S. & Pathak, V. K. Nuclear import of APOBEC3F-labeled HIV-1 preintegration complexes. Proc. Natl Acad. Sci. USA 110, E4780–E4789 (2013).
  Article CAS PubMed Google Scholar
• Campbell, E. M., Perez, O., Anderson, J. L. & Hope, T. J. Visualization of a proteasome-independent intermediate during restriction of HIV-1 by rhesus TRIM5α. J. Cell Biol. 180, 549–561 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Campbell, E. M., Perez, O., Melar, M. & Hope, T. J. Labeling HIV-1 virions with two fluorescent proteins allows identification of virions that have productively entered the target cell. Virology 360, 286–293 (2007).
  Article CAS PubMed Google Scholar
• Thomas, J. A., Ott, D. E. & Gorelick, R. J. Efficiency of human immunodeficiency virus type 1 postentry infection processes: evidence against disproportionate numbers of defective virions. J. Virol. 81, 4367–4370 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Sayah, D. M., Sokolskaja, E., Berthoux, L. & Luban, J. Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature 430, 569–573 (2004). A paper detailing the first identification of the TRIM–Cyp restriction factor, which has become an important tool in the study of uncoating, given its ability to recognize CA and be inhibited by CsA.
  Article CAS PubMed Google Scholar
• Pornillos, O., Ganser-Pornillos, B. K. & Yeager, M. Atomic-level modelling of the HIV capsid. Nature 469, 424–427 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Luban, J. Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection. J. Virol. 81, 1054–1061 (2007).
  Article CAS PubMed Google Scholar
• Song, C. & Aiken, C. Analysis of human cell heterokaryons demonstrates that target cell restriction of cyclosporine-resistant human immunodeficiency virus type 1 mutants is genetically dominant. J. Virol. 81, 11946–11956 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Gaudin, R., Alencar, B. C., Arhel, N. & Benaroch, P. HIV trafficking in host cells: motors wanted! Trends Cell Biol. 23, 652–662 (2013).
  Article CAS PubMed Google Scholar