Increased cell-free mitochondrial DNA is a marker of ongoing inflammation and better neurocognitive function in virologically suppressed HIV-infected individuals

Josué Pérez-Santiago1, Michelli F. Oliveira1, Susanna R. Var2, Tyler R C Day3, Steven Paul Woods4, Sara Gianella1, Sanjay R. Mehta5
1University of California, San Diego, La Jolla, USA
2Western Michigan University, Kalamazoo, USA
3Washington University, St. Louis, USA
4University of Houston, Houston, USA
5Veterans Administration San Diego Healthcare System, San Diego, CA, USA

Tóm tắt

Từ khóa


Tài liệu tham khảo

Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799

Bofill M, Mocroft A, Lipman M, Medina E, Borthwick NJ, Sabin CA, Timms A, Winter M, Baptista L, Johnson MA, Lee CA, Phillips AN, Janossy G (1996) Increased numbers of primed activated CD8+CD38+CD45RO+ T cells predict the decline of CD4+ T cells in HIV-1-infected patients. AIDS 10:827–834

Cossarizza A, Pinti M, Nasi M, Gibellini L, Manzini S, Roat E, De Biasi S, Bertoncelli L, Montagna JP, Bisi L, Manzini L, Trenti T, Borghi V, Mussini C (2011) Increased plasma levels of extracellular mitochondrial DNA during HIV infection: a new role for mitochondrial damage-associated molecular patterns during inflammation. Mitochondrion 11:750–755

Erlandson KM, Allshouse AA, Jankowski CM, Lee EJ, Rufner KM, Palmer BE, Wilson CC, Mawhinney S, Kohrt WM, Campbell TB (2013) Association of Functional Impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy. J Infect Dis 208:249–259

Giorgi JV, Hultin LE, McKeating JA, Johnson TD, Owens B, Jacobson LP, Shih R, Lewis J, Wiley DJ, Phair JP, Wolinsky SM, Detels R (1999) Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 179:859–870

Gonzalez-Scarano F, Martin-Garcia J (2005) The neuropathogenesis of AIDS. Nat Rev Immunol 5:69–81

Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ, Makarewicz AJ, Bright IJ, Lucero MY, Hiddessen AL, Legler TC, Kitano TK, Hodel MR, Petersen JF, Wyatt PW, Steenblock ER, Shah PH, Bousse LJ, Troup CB, Mellen JC, Wittmann DK, Erndt NG, Cauley TH, Koehler RT, So AP, Dube S, Rose KA, Montesclaros L, Wang S, Stumbo DP, Hodges SP, Romine S, Milanovich FP, White HE, Regan JF, Karlin-Neumann GA, Hindson CM, Saxonov S, Colston BW (2011) High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem 83:8604–8610

Hunt PW, Martin JN, Sinclair E, Bredt B, Hagos E, Lampiris H, Deeks SG (2003) T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis 187:1534–1543

Iwasaki A, Medzhitov R (2010) Regulation of adaptive immunity by the innate immune system. Science 327:291–295

Joseph J, Colosi DA, Rao VR (2016). HIV-1 induced cns dysfunction: current overview and research priorities. Curr HIV Res 14:11

Little SJ, Frost SD, Wong JK, Smith DM, Pond SL, Ignacio CC, Parkin NT, Petropoulos CJ, Richman DD (2008) Persistence of transmitted drug resistance among subjects with primary human immunodeficiency virus infection. J Virol 82:5510–5518

Mahalingam M, Peakman M, Davies ET, Pozniak A, McManus TJ, Vergani D (1993) T cell activation and disease severity in HIV infection. Clin Exp Immunol 93:337–343

Nasi M, Pinti M, De Biasi S, Gibellini L, Ferraro D, Mussini C, Cossarizza A (2014) Aging with HIV infection: a journey to the center of inflamm AIDS, immunosenescence and neuro HIV. Immunol Lett 162:329–333

Oliveira MF, Murrel B, Perez-Santiago J, Vargas M, Ellis RJ, Letendre S, Grant I, Smith DM, Woods SP, Gianella S (2015) Circulating HIV DNA correlates with neurocognitive impairment in older HIV-infected adults on suppressive ART. Sci Rep 5:17094

Perez-Santiago J, De Oliveira MF, Murrell B, Var SR, Day TRC, Suben JD, Woods SP, Ellis RJ, Gianella S, Mehta SR (2015) Mitochondrial DNA, neurologic and systemic inflammation, and immune dysregulation. Conference on retroviruses and opportunistic infections. Seattle, WA

Perez-Santiago J, Schrier RD, de Oliveira MF, Gianella S, Var SR, Day TR, Ramirez-Gaona M, Suben JD, Murrell B, Massanella M, Cherner M, Smith DM, Ellis RJ, Letendre SL, Mehta SR (2016) Cell-free mitochondrial DNA in CSF is associated with early viral rebound, inflammation, and severity of neurocognitive deficits in HIV infection. J Neurovirol 22:191–200

Podlesniy P, Figueiro-Silva J, Llado A, Antonell A, Sanchez-Valle R, Alcolea D, Lleo A, Molinuevo JL, Serra N, Trullas R (2013) Low cerebrospinal fluid concentration of mitochondrial DNA in preclinical Alzheimer disease. Ann Neurol 74:655–668

Podlesniy P, Llorens F, Golanska E, Sikorska B, Liberski P, Zerr I, Trullas R (2016). Mitochondrial DNA differentiates Alzheimer’s disease from Creutzfeldt-Jakob disease. Alzheimers Dement 12:546–555

Pyle A, Brennan R, Kurzawa-Akanbi M, Yarnall A, Thouin A, Mollenhauer B, Burn D, Chinnery PF, Hudson G (2015) Reduced cerebrospinal fluid mitochondrial DNA is a biomarker for early-stage Parkinson’s disease. Ann Neurol 78:1000–1004

Pyle A, Anugrha H, Kurzawa-Akanbi M, Yarnall A, Burn D, Hudson G (2016) Reduced mitochondrial DNA copy number is a biomarker of Parkinson’s disease. Neurobiol Aging 38(216):e7–10

R Core Team (2016). R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/

Rice AC, Keeney PM, Algarzae NK, Ladd AC, Thomas RR, Bennett JP Jr (2014) Mitochondrial DNA copy numbers in pyramidal neurons are decreased and mitochondrial biogenesis transcriptome signaling is disrupted in Alzheimer’s disease hippocampi. J Alzheimers Dis 40:319–330

Sheppard DP, Iudicello JE, Bondi MW, Doyle KL, Morgan EE, Massman PJ, Gilbert PE, Woods SP (2015) Elevated rates of mild cognitive impairment in HIV disease. J Neurovirol 21:576–584

Var SR, Day TR, Vitomirov A, Smith DM, Soontornniyomkij V, Moore DJ, Achim CL, Mehta SR, Perez-Santiago J (2016). Mitochondrial injury and cognitive function in HIV infection and methamphetamine use. AIDS 30:839–848

Walko TD 3rd, Bola RA, Hong JD, Au AK, Bell MJ, Kochanek PM, Clark RS, Aneja RK (2014) Cerebrospinal fluid mitochondrial DNA: a novel DAMP in pediatric traumatic brain injury. Shock 41:499–503

Wallet MA, Buford TW, Joseph AM, Sankuratri M, Leeuwenburgh C, Pahor M, Manini T, Sleasman JW, Goodenow MM (2015) Increased inflammation but similar physical composition and function in older-aged, HIV-1 infected subjects. BMC Immunol 16:43

Wang HC, Yang TM, Lin WC, Lin YJ, Tsai NW, Liou CW, Kwan AL, Lu CH (2013) The value of serial plasma and cerebrospinal fluid nuclear and mitochondrial deoxyribonucleic acid levels in aneurysmal subarachnoid hemorrhage. J Neurosurg 118:13–19

Zayyad Z, Spudich S (2015) Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND). Curr HIV/AIDS Rep 12:16–24

Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104–107