Targeting type I interferon-mediated activation restores immune function in chronic HIV infection

Journal of Clinical Investigation

Volumn 127, Issue 1, 2017, Pages 260-268

  Zhen, Anjie ^a   Rezek, Valerie ^a   Youn, Cindy ^a   Lam, Brianna ^a   Chang, Nelson ^a   Rick, Jonathan ^a   Carrillo, Mayra ^a   Martin, Heather ^a   Kasparian, Saro ^a   Syed, Philip ^a   Rice, Nicholas ^a   Brooks, David G ^b,c   Kitchen, Scott G ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b PRINCESS MARGARET HOSPITAL   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED PROTHROMBIN COMPLEX; BLOCKING ANTIBODY; CD38 ANTIGEN; CD4 ANTIGEN; EMTRICITABINE; ENVELOPE PROTEIN; GAG PROTEIN; HLA DR ANTIGEN; INTERFERON; INTERFERON ANTIBODY; INTERFERON RECEPTOR 2 BLOCKING ANTIBODY; INTERFERON REGULATORY FACTOR 2; INTERFERON REGULATORY FACTOR 7; INTERLEUKIN 2; IONOMYCIN; MITOGENIC AGENT; MX1 PROTEIN; NEF PROTEIN; OAS1 PROTEIN; POL PROTEIN; PROGRAMMED DEATH 1 LIGAND 1; PROTEIN; RALTEGRAVIR; TENOFOVIR DISOPROXIL; TIM 3 PROTEIN; UNCLASSIFIED DRUG; ANTIRETROVIRUS AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; COMPARATIVE STUDY; CONTROLLED STUDY; ENZYME ACTIVATION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; RECEPTOR BLOCKING; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; VIRUS LOAD; VIRUS REPLICATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHRONIC DISEASE; DISEASE MODEL; GENETICS; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; KNOCKOUT MOUSE; PATHOLOGY;

ANIMALS; ANTI-RETROVIRAL AGENTS; CD8-POSITIVE T-LYMPHOCYTES; CHRONIC DISEASE; DISEASE MODELS, ANIMAL; HIV INFECTIONS; HIV-1; HUMANS; INTERFERON TYPE I; MICE; MICE, KNOCKOUT;

EID: 85008331088     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI89488     Document Type: Article

References (31)

1. Jones RB, et al. Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection. J Exp Med. 2008;205(12):2763-2779.
2. McMichael AJ, Rowland-Jones SL. Cellular immune responses to HIV. Nature. 2001;410(6831):980-987.
3. Jin HT, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A. 2010;107(33):14733-14738.
4. Khaitan A, Unutmaz D. Revisiting immune exhaustion during HIV infection. Curr HIV/AIDS Rep. 2011;8(1):4-11.
5. Wilson EB, et al. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science. 2013;340(6129):202-207.
6. Ng CT, Snell LM, Brooks DG, Oldstone MB. Networking at the level of host immunity: immune cell interactions during persistent viral infections. Cell Host Microbe. 2013;13(6):652-664.
7. Jacquelin B, et al. Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J Clin Invest. 2009;119(12):3544-3555.
8. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486-499.
9. Denton PW, et al. Generation of HIV latency in humanized BLT mice. J Virol. 2012;86(1):630-634.
10. Wilson EB, Brooks DG. Decoding the complexity of type I interferon to treat persistent viral infections. Trends Microbiol. 2013;21(12):634-640.
11. Deng K, et al. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature. 2015;517(7534):381-385.
12. Hazenberg MD, et al. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS. 2003;17(13):1881-1888.
13. Rajasuriar R, Khoury G, Kamarulzaman A, French MA, Cameron PU, Lewin SR. Persistent immune activation in chronic HIV infection: do any interventions work? AIDS. 2013;27(8):1199-1208.
14. Sauce D, Elbim C, Appay V. Monitoring cellular immune markers in HIV infection: from activation to exhaustion. Curr Opin HIV AIDS. 2013;8(2):125-131.
15. Marsden MD, et al. HIV latency in the humanized BLT mouse. J Virol. 2012;86(1):339-347.
16. Brooks DG, Arlen PA, Gao L, Kitchen CM, Zack JA. Identification of T cell-signaling pathways that stimulate latent HIV in primary cells. Proc Natl Acad Sci U S A. 2003;100(22):12955-12960.
17. Teijaro JR, et al. Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science. 2013;340(6129):207-211.
18. Sandler NG, et al. Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature. 2014;511(7511):601-605.
19. Brooks DG, Kitchen SG, Kitchen CM, Scripture- Adams DD, Zack JA. Generation of HIV latency during thymopoiesis. Nat Med. 2001;7(4):459-464.
20. 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. 2013;207(2):213-222.
21. Asmuth DM, et al. Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial. J Infect Dis. 2010;201(11):1686-1696.
22. Bruner KM, et al. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat Med. 2016;22(9):1043-1049.
23. Acchioni C, Marsili G, Perrotti E, Remoli AL, Sgarbanti M, Battistini A. Type I IFN - A blunt spear in fighting HIV-1 infection. Cytokine Growth Factor Rev. 2015;26(2):143-158.
24. Larsson M, et al. Molecular signatures of T-cell inhibition in HIV-1 infection. Retrovirology. 2013;10:31.
25. Rodríguez-García M, et al. Expression of PD-L1 and PD-L2 on human macrophages is upregulated by HIV-1 and differentially modulated by IL-10. J Leukoc Biol. 2011;89(4):507-515.
26. Brainard DM, et al. Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice. J Virol. 2009;83(14):7305-7321.
27. Planès R, BenMohamed L, Leghmari K, Delobel P, Izopet J, Bahraoui E. HIV-1 Tat protein induces PD-L1 (B7-H1) expression on dendritic cells through tumor necrosis factor α- And tolllike receptor 4-mediated mechanisms. J Virol. 2014;88(12):6672-6689.
28. Dudek TE, et al. Rapid evolution of HIV-1 to functional CD8+ T cell responses in humanized BLT mice. Sci Transl Med. 2012;4(143):143.
29. Kitchen SG, et al. Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice. PLoS One. 2009;4(12):e8208.
30. Kitchen SG, et al. In vivo suppression of HIV by antigen specific T cells derived from engineered hematopoietic stem cells. PLoS Pathog. 2012;8(4):e1002649.
31. Goujon C, Malim MH. Characterization of the alpha interferon-induced postentry block to HIV-1 infection in primary human macrophages and T cells. J Virol. 2010;84(18):9254-9266.