Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6

  1. Cabrera-Rodríguez, Romina 1
  2. Pérez-Yanes, Silvia 1
  3. Montelongo, Rafaela
  4. Lorenzo-Salazar, José M.
  5. Estévez-Herrera, Judith 1
  6. García-Luis, Jonay 1
  7. Íñigo-Campos, Antonio
  8. Rubio-Rodríguez, Luis A.
  9. Muñoz-Barrera, Adrián
  10. Trujillo-González, Rodrigo 1
  11. Dorta-Guerra, Roberto 1
  12. Casado, Concha
  13. Pernas, María
  14. Blanco, Julià
  15. Flores, Carlos 1
  16. Valenzuela-Fernández, Agustín 1
  1. 1 Universidad de La Laguna
    info

    Universidad de La Laguna

    San Cristobal de La Laguna, España

    ROR https://ror.org/01r9z8p25

Journal:
International Journal of Molecular Sciences

ISSN: 1422-0067

Year of publication: 2022

Volume: 23

Issue: 11

Pages: 6180

Type: Article

DOI: 10.3390/IJMS23116180 GOOGLE SCHOLAR lock_openOpen access editor

Abstract

The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism. Consistently, using an HIV-1 Env-mediated cell-to-cell fusion model, the overexpression of TDP-43 levels negatively affected viral Env fusion capacity. Silencing of endogenous TDP-43 significantly decreased HDAC6 levels and increased the fusogenic and infection activities of the HIV-1 Env. Using pseudovirus bearing primary viral Envs from HIV-1 individuals, overexpression of wt-TDP-43 strongly reduced the infection activity of Envs from viremic non-progressors (VNP) and rapid progressors (RP) patients down to the levels of the inefficient HIV-1 Envs observed in long-term non-progressor elite controllers (LTNP-EC). On the contrary, silencing endogenous TDP-43 significantly favored the infectivity of primary Envs from VNP and RP individuals, and notably increased the infection of those from LTNP-EC. Taken together, our results indicate that TDP-43 shapes cell permissivity to HIV-1 infection, affecting viral Env fusion and infection capacities by altering the HDAC6 levels and associated tubulin-deacetylase anti-HIV-1 activity.

Bibliographic References

  • 1. Brown, A.-L.; Wilkins, O.G.; Keuss, M.J.; Hill, S.E.; Zanovello, M.; Lee, W.C.; Bampton, A.; Lee, F.C.Y.; Masino, L.; Qi, Y.A.; et al. TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A. Nature 2022, 603, 131–137. [Google Scholar] [CrossRef] [PubMed]
  • 2. Ma, X.R.; Prudencio, M.; Koike, Y.; Vatsavayai, S.C.; Kim, G.; Harbinski, F.; Briner, A.; Rodriguez, C.M.; Guo, C.; Akiyama, T.; et al. TDP-43 represses cryptic exon inclusion in the FTD–ALS gene UNC13A. Nature 2022, 603, 124–130. [Google Scholar] [CrossRef] [PubMed]
  • 3. Buratti, E.; Baralle, F.E. The multiple roles of TDP-43 in pre-mRNA processing and gene expression regulation. RNA Biol. 2010, 7, 420–429. [Google Scholar] [CrossRef]
  • 4. Colombrita, C.; Onesto, E.; Megiorni, F.; Pizzuti, A.; Baralle, F.E.; Buratti, E.; Silani, V.; Ratti, A. TDP-43 and FUS RNA-binding Proteins Bind Distinct Sets of Cytoplasmic Messenger RNAs and Differently Regulate Their Post-transcriptional Fate in Motoneuron-like Cells. J. Biol. Chem. 2012, 287, 15635–15647. [Google Scholar] [CrossRef]
  • 5. Tollervey, J.R.; Curk, T.; Rogelj, B.; Briese, M.; Cereda, M.; Kayikci, M.; König, J.; Hortobágyi, T.; Nishimura, A.L.; Župunski, V.; et al. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat. Neurosci. 2011, 14, 452–458. [Google Scholar] [CrossRef]
  • 6. Polymenidou, M.; Lagier-Tourenne, C.; Hutt, K.R.; Huelga, S.C.; Moran, J.; Liang, T.Y.; Ling, S.-C.; Sun, E.; Wancewicz, E.; Mazur, C.; et al. Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat. Neurosci. 2011, 14, 459–468. [Google Scholar] [CrossRef] [PubMed]
  • 7. Kawahara, Y.; Mieda-Sato, A. TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc. Natl. Acad. Sci. USA 2012, 109, 3347–3352. [Google Scholar] [CrossRef] [PubMed]
  • 8. Highley, J.R.; Kirby, J.; Jansweijer, J.A.; Webb, P.S.; Hewamadduma, C.A.; Heath, P.R.; Higginbottom, A.; Raman, R.; Ferraiuolo, L.; Cooper-Knock, J.; et al. Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones. Neuropathol. Appl. Neurobiol. 2014, 40, 670–685. [Google Scholar] [CrossRef]
  • 9. Ma, X.; Ying, Y.; Xie, H.; Liu, X.; Wang, X.; Li, J. The Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer. Front. Oncol. 2021, 11, 755096. [Google Scholar] [CrossRef]
  • 10. Sephton, C.F.; Cenik, C.; Kucukural, A.; Dammer, E.B.; Cenik, B.; Han, Y.; Dewey, C.M.; Roth, F.P.; Herz, J.; Peng, J.; et al. Identification of Neuronal RNA Targets of TDP-43-containing Ribonucleoprotein Complexes. J. Biol. Chem. 2011, 286, 1204–1215. [Google Scholar] [CrossRef]
  • 11. Fiesel, F.C.; Voigt, A.; Weber, S.S.; Van den Haute, C.; Waldenmaier, A.; Görner, K.; Walter, M.; Anderson, M.L.; Kern, J.V.; Rasse, T.M.; et al. Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase. EMBO J. 2010, 29, 209–221. [Google Scholar] [CrossRef] [PubMed]
  • 12. Simões-Pires, C.; Zwick, V.; Nurisso, A.; Schenker, E.; Carrupt, P.-A.; Cuendet, M. HDAC6 as a target for neurodegenerative diseases: What makes it different from the other HDACs? Mol. Neurodegener. 2013, 8, 7. [Google Scholar] [CrossRef] [PubMed]
  • 13. Gao, J.; Wang, L.; Huntley, M.L.; Perry, G.; Wang, X. Pathomechanisms of TDP-43 in neurodegeneration. J. Neurochem. 2018, 146, 7–20. [Google Scholar] [CrossRef] [PubMed]
  • 14. Guo, W.; Bosch, L.V.D. Therapeutic potential of HDAC6 in amyotrophic lateral sclerosis. Cell Stress 2017, 2, 14–16. [Google Scholar] [CrossRef]
  • 15. Odagiri, S.; Tanji, K.; Mori, F.; Miki, Y.; Kakita, A.; Takahashi, H.; Wakabayashi, K. Brain expression level and activity of HDAC6 protein in neurodegenerative dementia. Biochem. Biophys. Res. Commun. 2013, 430, 394–399. [Google Scholar] [CrossRef]
  • 16. Lemos, M.; Stefanova, N. Histone Deacetylase 6 and the Disease Mechanisms of α-Synucleinopathies. Front. Synaptic Neurosci. 2020, 12, 586453. [Google Scholar] [CrossRef]
  • 17. Trzeciakiewicz, H.; Ajit, D.; Tseng, J.-H.; Chen, Y.; Ajit, A.; Tabassum, Z.; Lobrovich, R.; Peterson, C.; Riddick, N.V.; Itano, M.S.; et al. An HDAC6-dependent surveillance mechanism suppresses tau-mediated neurodegeneration and cognitive decline. Nat. Commun. 2020, 11, 5522. [Google Scholar] [CrossRef]
  • 18. Cykowski, M.D.; Powell, S.Z.; Peterson, L.; Appel, J.W.; Rivera, A.L.; Takei, H.; Chang, E.; Appel, S.H. Clinical Significance of TDP-43 Neuropathology in Amyotrophic Lateral Sclerosis. J. Neuropathol. Exp. Neurol. 2017, 76, 402–413. [Google Scholar] [CrossRef]
  • 19. Kwong, L.K.; Neumann, M.; Sampathu, D.M.; Lee, V.M.-Y.; Trojanowski, J.Q. TDP-43 proteinopathy: The neuropathology underlying major forms of sporadic and familial frontotemporal lobar degeneration and motor neuron disease. Acta Neuropathol. 2007, 114, 63–70. [Google Scholar] [CrossRef]
  • 20. Ou, S.H.; Wu, F.; Harrich, D.; García-Martínez, L.F.; Gaynor, R.B. Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. J. Virol. 1995, 69, 3584–3596. [Google Scholar] [CrossRef]
  • 21. Wang, H.-Y.; Wang, I.-F.; Bose, J.; Shen, C.-K. Structural diversity and functional implications of the eukaryotic TDP gene family. Genomics 2004, 83, 130–139. [Google Scholar] [CrossRef]
  • 22. Buratti, E.; Baralle, F.E. Characterization and Functional Implications of the RNA Binding Properties of Nuclear Factor TDP-43, a Novel Splicing Regulator ofCFTR Exon. J. Biol. Chem. 2001, 276, 36337–36343. [Google Scholar] [CrossRef]
  • 23. Nehls, J.; Koppensteiner, H.; Brack-Werner, R.; Floss, T.; Schindler, M. HIV-1 Replication in Human Immune Cells Is Independent of TAR DNA Binding Protein 43 (TDP-43) Expression. PLoS ONE 2014, 9, e105478. [Google Scholar] [CrossRef] [PubMed]
  • 24. Aguilera, A.; Aroeira, L.G.S.; Ramírez-Huesca, M.; Lozano, M.-L.P.; Cirugeda, A.; Bajo, M.; Del Peso, G.; Valenzuela-Fernández, A.; Sánchez-Tomero, J.; Cabrera, M.L.; et al. Effects of Rapamycin on the Epithelial-to-mesenchymal Transition of Human Peritoneal Mesothelial Cells. Int. J. Artif. Organs 2005, 28, 164–169. [Google Scholar] [CrossRef]
  • 25. Valera, M.-S.; De Armas-Rillo, L.; Barroso-González, J.; Ziglio, S.; Batisse, J.; Dubois, N.; Marrero-Hernández, S.; Borel, S.; García-Expósito, L.; Biard-Piechaczyk, M.; et al. The HDAC6/APOBEC3G complex regulates HIV-1 infectiveness by inducing Vif autophagic degradation. Retrovirology 2015, 12, 1–26. [Google Scholar] [CrossRef] [PubMed]
  • 26. Rodríguez, R.C.; Hebmann, V.; Marfil, S.; Pernas, M.; Marrero-Hernández, S.; Cabrera, C.; Urrea, V.; Casado, C.; Olivares, I.; Márquez-Arce, D.; et al. HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic. Sci. Rep. 2019, 9, 5544. [Google Scholar] [CrossRef] [PubMed]
  • 27. Cabrera-Rodríguez, R.; Pérez-Yanes, S.; Estévez-Herrera, J.; Márquez-Arce, D.; Cabrera, C.; Espert, L.; Blanco, J.; Valenzuela-Fernández, A. The Interplay of HIV and Autophagy in Early Infection. Front. Microbiol. 2021, 12, 661446. [Google Scholar] [CrossRef]
  • 28. Barrero-Villar, M.; Barroso-Gonzalez, J.; Cabrero, J.R.; Gordon-Alonso, M.; Álvarez-Losada, S.; Muñoz-Fernández, M.; Sánchez-Madrid, F.; Valenzuela-Fernández, A. PI4P5-Kinase Iα Is Required for Efficient HIV-1 Entry and Infection of T Cells. J. Immunol. 2008, 181, 6882–6888. [Google Scholar] [CrossRef]
  • 29. Casado, C.; Marrero-Hernández, S.; Márquez-Arce, D.; Pernas, M.; Marfil, S.; Borràs-Grañana, F.; Olivares, I.; Cabrera-Rodríguez, R.; Valera, M.-S.; de Armas-Rillo, L.; et al. Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers. mBio 2018, 9, e02338-17. [Google Scholar] [CrossRef]
  • 30. Winton, M.J.; Igaz, L.M.; Wong, M.M.; Kwong, L.K.; Trojanowski, J.Q.; Lee, V.M.-Y. Disturbance of Nuclear and Cytoplasmic TAR DNA-binding Protein (TDP-43) Induces Disease-like Redistribution, Sequestration, and Aggregate Formation. J. Biol. Chem. 2008, 283, 13302–13309. [Google Scholar] [CrossRef]
  • 31. Wang, C.; Duan, Y.; Duan, G.; Wang, Q.; Zhang, K.; Deng, X.; Qian, B.; Gu, J.; Ma, Z.; Zhang, S.; et al. Stress Induces Dynamic, Cytotoxicity-Antagonizing TDP-43 Nuclear Bodies via Paraspeckle LncRNA NEAT1-Mediated Liquid-Liquid Phase Separation. Mol. Cell 2020, 79, 443–458. [Google Scholar] [CrossRef] [PubMed]
  • 32. Besnard-Guérin, C. Cytoplasmic localization of amyotrophic lateral sclerosis-related TDP-43 proteins modulates stress granule formation. Eur. J. Neurosci. 2020, 52, 3995–4008. [Google Scholar] [CrossRef] [PubMed]
  • 33. Portran, D.; Schaedel, L.; Xu, Z.; Théry, L.S.M.; Nachury, D.P.Z.X.M.V. Tubulin acetylation protects long-lived microtubules against mechanical ageing. Nat. Cell Biol. 2017, 19, 391–398. [Google Scholar] [CrossRef] [PubMed]
  • 34. Szyk, A.; Deaconescu, A.M.; Spector, J.; Goodman, B.; Valenstein, M.L.; Ziolkowska, N.E.; Kormendi, V.; Grigorieff, N.; Roll-Mecak, A. Molecular Basis for Age-Dependent Microtubule Acetylation by Tubulin Acetyltransferase. Cell 2014, 157, 1405–1415. [Google Scholar] [CrossRef]
  • 35. Eshun-Wilson, L.; Zhang, R.; Portran, D.; Nachury, M.V.; Toso, D.B.; Löhr, T.; Vendruscolo, M.; Bonomi, M.; Fraser, J.S.; Nogales, E. Effects of α-tubulin acetylation on microtubule structure and stability. Proc. Natl. Acad. Sci. USA 2019, 116, 10366–10371. [Google Scholar] [CrossRef] [PubMed]
  • 36. Howes, S.C.; Alushin, G.M.; Shida, T.; Nachury, M.V.; Nogales, E. Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure. Mol. Biol. Cell 2014, 25, 257–266. [Google Scholar] [CrossRef] [PubMed]
  • 37. Magiera, M.M.; Singh, P.; Gadadhar, S.; Janke, C. Tubulin Posttranslational Modifications and Emerging Links to Human Disease. Cell 2018, 173, 1323–1327. [Google Scholar] [CrossRef]
  • 38. Maruta, H.; Greer, K.; Rosenbaum, J.L. The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules. J. Cell Biol. 1986, 103, 571–579. [Google Scholar] [CrossRef]
  • 39. Ledizet, M.; Piperno, G. Cytoplasmic microtubules containing acetylated alpha-tubulin in Chlamydomonas reinhardtii: Spatial arrangement and properties. J. Cell Biol. 1986, 103, 13–22. [Google Scholar] [CrossRef]
  • 40. Foster, A.D.; Flynn, L.L.; Cluning, C.; Cheng, F.; Davidson, J.M.; Lee, A.; Polain, N.; Mejzini, R.; Farrawell, N.; Yerbury, J.J.; et al. p62 overexpression induces TDP-43 cytoplasmic mislocalisation, aggregation and cleavage and neuronal death. Sci. Rep. 2021, 11, 11474. [Google Scholar] [CrossRef]
  • 41. Brady, O.A.; Meng, P.; Zheng, Y.; Mao, Y.; Hu, F. Regulation of TDP-43 aggregation by phosphorylation andp62/SQSTM. J. Neurochem. 2011, 116, 248–259. [Google Scholar] [CrossRef] [PubMed]
  • 42. Fazal, R.; Boeynaems, S.; Swijsen, A.; De Decker, M.; Fumagalli, L.; Moisse, M.; Vanneste, J.; Guo, W.; Boon, R.; Vercruysse, T.; et al. HDAC6 inhibition restores TDP-43 pathology and axonal transport defects in human motor neurons with TARDBP mutations. EMBO J. 2021, 40, e106177. [Google Scholar] [CrossRef]
  • 43. Hebron, M.L.; Lonskaya, I.; Sharpe, K.; Weerasinghe, P.; Algarzae, N.K.; Shekoyan, A.R.; Moussa, C.E.-H. Parkin Ubiquitinates Tar-DNA Binding Protein-43 (TDP-43) and Promotes Its Cytosolic Accumulation via Interaction with Histone Deacetylase 6 (HDAC6). J. Biol. Chem. 2013, 288, 4103–4115. [Google Scholar] [CrossRef]
  • 44. Yan, J.; Seibenhener, M.L.; Calderilla-Barbosa, L.; Diaz-Meco, M.-T.; Moscat, J.; Jiang, J.; Wooten, M.W.; Wooten, M.C. SQSTM1/p62 Interacts with HDAC6 and Regulates Deacetylase Activity. PLoS ONE 2013, 8, e76016. [Google Scholar] [CrossRef] [PubMed]
  • 45. Barrero-Villar, M.; Cabrero, J.R.; Gordón-Alonso, M.; Barroso-Gonzalez, J.; Álvarez-Losada, S.; Muñoz-Fernández, M.A.; Sánchez-Madrid, F.; Valenzuela-Fernández, A. Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes. J. Cell Sci. 2009, 122, 103–113. [Google Scholar] [CrossRef] [PubMed]
  • 46. Pleskoff, O.; Tréboute, C.; Brelot, A.; Heveker, N.; Seman, M.; Alizon, M. Identification of a Chemokine Receptor Encoded by Human Cytomegalovirus as a Cofactor for HIV-1 Entry. Science 1997, 276, 1874–1878. [Google Scholar] [CrossRef]
  • 47. Schwartz, O.; Alizon, M.; Heard, J.-M.; Danos, O. Impairment of T Cell Receptor-Dependent Stimulation in CD4+ Lymphocytes after Contact with Membrane-Bound HIV-1 Envelope Glycoprotein. Virology 1994, 198, 360–365. [Google Scholar] [CrossRef] [PubMed]
  • 48. Pérez-Yanes, S.; Pernas, M.; Marfil, S.; Cabrera-Rodríguez, R.; Ortiz, R.; Urrea, V.; Rovirosa, C.; Estévez-Herrera, J.; Olivares, I.; Casado, C.; et al. The Characteristics of the HIV-1 Env Glycoprotein Are Linked With Viral Pathogenesis. Front. Microbiol. 2022, 13, 763039. [Google Scholar] [CrossRef]
  • 49. Rosas-Umbert, M.; Llano, A.; Bellido, R.; Olvera, A.; Ruiz-Riol, M.; Rocafort, M.; Fernández, M.A.; Cobarsi, P.; Crespo, M.; Dorrell, L.; et al. Mechanisms of Abrupt Loss of Virus Control in a Cohort of Previous HIV Controllers. J. Virol. 2019, 93, e01436-18. [Google Scholar] [CrossRef]
  • 50. Borrell, M.; Fernández, I.; Etcheverrry, F.; Ugarte, A.; Plana, M.; Leal, L.; García, F. High rates of long-term progression in HIV-1-positive elite controllers. J. Int. AIDS Soc. 2021, 24, e25675. [Google Scholar] [CrossRef]
  • 51. Marrero-Hernández, S.; Márquez-Arce, D.; Cabrera-Rodriguez, R.; Estévez-Herrera, J.; Pérez-Yanes, S.; Barroso-Gonzalez, J.; Madrid, R.; Machado, J.-D.; Blanco, J.; Valenzuela-Fernández, A. HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection. Front. Microbiol. 2019, 10, 2437. [Google Scholar] [CrossRef] [PubMed]
  • 52. Valenzuela-Fernández, A.; Álvarez, S.; Gordon-Alonso, M.; Barrero, M.; Ursa, A.; Cabrero, J.R.; Fernández, G.; Naranjo-Suárez, S.; Yáñez-Mó, M.; Serrador, J.M.; et al. Histone Deacetylase 6 Regulates Human Immunodeficiency Virus Type 1 Infection. Mol. Biol. Cell 2005, 16, 5445–5454. [Google Scholar] [CrossRef] [PubMed]
  • 53. Blanco, J.; Barretinaa, J.; Ferri, K.F.; Jacototbc, E.; Gutiérreza, A.; Armand-Ugon, M.; Cabreraa, C.; Kroemerb, G.; Cloteta, B.; Esté, J.A. Cell-Surface-Expressed HIV-1 Envelope Induces the Death of CD4 T Cells during GP41-Mediated Hemifusion-like Events. Virology 2003, 305, 318–329. [Google Scholar] [CrossRef] [PubMed]
  • 54. Espert, L.; Varbanov, M.; Robert-Hebmann, V.; Sagnier, S.; Robbins, I.; Sanchez, F.; Lafont, V.; Biard-Piechaczyk, M. Differential Role of Autophagy in CD4 T Cells and Macrophages during X4 and R5 HIV-1 Infection. PLoS ONE 2009, 4, e5787. [Google Scholar] [CrossRef] [PubMed]
  • 55. Fung, G.; Shi, J.; Deng, H.; Hou, J.; Wang, C.; Hong, A.; Zhang, J.; Jia, W.; Luo, H. Cytoplasmic translocation, aggregation, and cleavage of TDP-43 by enteroviral proteases modulate viral pathogenesis. Cell Death Differ. 2015, 22, 2087–2097. [Google Scholar] [CrossRef]
  • 56. Manghera, M.; Ferguson-Parry, J.; Lin, R.; Douville, R.N. NF-κB and IRF1 Induce Endogenous Retrovirus K Expression via Interferon-Stimulated Response Elements in Its 5′ Long Terminal Repeat. J. Virol. 2016, 90, 9338–9349. [Google Scholar] [CrossRef]
  • 57. Douville, R.; Liu, J.; Rothstein, J.; Nath, A. Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis. Ann. Neurol. 2011, 69, 141–151. [Google Scholar] [CrossRef]
  • 58. Li, W.; Lee, M.-H.; Henderson, L.; Tyagi, R.; Bachani, M.; Steiner, J.; Campanac, E.; Hoffman, D.A.; von Geldern, G.; Johnson, K.; et al. Human endogenous retrovirus-K contributes to motor neuron disease. Sci. Transl. Med. 2015, 7, 307ra153. [Google Scholar] [CrossRef]
  • 59. Janssens, J.; Van Broeckhoven, C. Pathological mechanisms underlying TDP-43 driven neurodegeneration in FTLD-ALS spectrum disorders. Hum. Mol. Genet. 2013, 22, R77–R87. [Google Scholar] [CrossRef]
  • 60. Bhat, R.K.; Rudnick, W.; Antony, J.M.; Maingat, F.; Ellestad, K.K.; Wheatley, B.M.; Tönjes, R.R.; Power, C. Human Endogenous Retrovirus-K(II) Envelope Induction Protects Neurons during HIV/AIDS. PLoS ONE 2014, 9, e97984. [Google Scholar] [CrossRef]
  • 61. Douville, R.N.; Nath, A. Human Endogenous Retrovirus-K and TDP-43 Expression Bridges ALS and HIV Neuropathology. Front. Microbiol. 2017, 8, 1986. [Google Scholar] [CrossRef] [PubMed]
  • 62. Wenzel, E.D.; Speidell, A.; Flowers, S.A.; Wu, C.; Avdoshina, V.; Mocchetti, I. Histone deacetylase 6 inhibition rescues axonal transport impairments and prevents the neurotoxicity of HIV-1 envelope protein gp120. Cell Death Dis. 2019, 10, 674. [Google Scholar] [CrossRef] [PubMed]
  • 63. Valenzuela-Fernández, A.; Cabrero, J.R.; Serrador, J.M.; Sánchez-Madrid, F. HDAC6: A key regulator of cytoskeleton, cell migration and cell–cell interactions. Trends Cell Biol. 2008, 18, 291–297. [Google Scholar] [CrossRef]
  • 64. Trkola, A.; Matthews, J.; Gordon, C.; Ketas, T.; Moore, J.P. A Cell Line-Based Neutralization Assay for Primary Human Immunodeficiency Virus Type 1 Isolates That Use either the CCR5 or the CXCR4 Coreceptor. J. Virol. 1999, 73, 8966–8974. [Google Scholar] [CrossRef]
  • 65. Barroso-González, J.; García-Expósito, L.; Puigdomènech, I.; De Armas-Rillo, L.; Machado, J.-D.; Blanco, J.; Valenzuela-Fernández, A. Viral infection: Moving through complex and dynamic cell-membrane structures. Commun. Integr. Biol. 2011, 4, 398–408. [Google Scholar] [CrossRef]
  • 66. García-Expósito, L.; Ziglio, S.; Barroso-González, J.; de Armas-Rillo, L.; Valera, M.-S.; Zipeto, D.; Machado, J.-D.; Valenzuela-Fernández, A. Gelsolin activity controls efficient early HIV-1 infection. Retrovirology 2013, 10, 39. [Google Scholar] [CrossRef] [PubMed]
  • 67. Callebaut, C.; Jacotot, E.; Krust, B.; Guichard, G.; Blanco, J.; Valenzuela, A.; Svab, J.; Muller, S.; Briand, J.-P.; Hovanessian, A.G. Pseudopeptide TASP Inhibitors of HIV Entry Bind Specifically to a 95-kDa Cell Surface Protein. J. Biol. Chem. 1997, 272, 7159–7166. [Google Scholar] [CrossRef] [PubMed]
  • 68. Patro, R.; Duggal, G.; Love, M.I.; Irizarry, R.A.; Kingsford, C. Salmon provides fast and bias-aware quantification of transcript expression. Nat. Methods 2017, 14, 417–419. [Google Scholar] [CrossRef]
  • 69. Dobin, A.; Davis, C.A.; Schlesinger, F.; Drenkow, J.; Zaleski, C.; Jha, S.; Batut, P.; Chaisson, M.; Gingeras, T.R. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 2013, 29, 15–21. [Google Scholar] [CrossRef]
  • 70. Okonechnikov, K.; Conesa, A.; García-Alcalde, F. Qualimap 2: Advanced multi-sample quality control for high-throughput sequencing data. Bioinformatics 2016, 32, 292–294. [Google Scholar] [CrossRef]