Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins

被引：30

作者：

Bulanova, Daria ^{[1
]}

Ianevski, Aleksandr ^{[1
]}

Bugai, Andrii ^{[2
]}

Akimov, Yevhen ^{[1
]}

Kuivanen, Suvi ^{[3
]}

Paavilainen, Henrik ^{[4
]}

Kakkola, Laura ^{[4
]}

Nandania, Jatin ^{[1
]}

Turunen, Laura ^{[1
]}

Ohman, Tiina ^{[5
]}

Ala-Hongisto, Hanna ^{[6
]}

Pesonen, Hanna M. ^{[6
]}

Kuisma, Marika S. ^{[6
]}

Honkimaa, Anni ^{[7
]}

Walton, Emma L. ^{[8
]}

Oksenych, Valentyn ^{[8
]}

Lorey, Martina B. ^{[9
,10
]}

Guschin, Dmitry ^{[11
]}

Shim, Jungmin ^{[11
]}

Kim, Jinhee ^{[11
]}

Than, Thoa T. ^{[11
]}

Chang, So Young ^{[11
]}

Hukkanen, Veijo ^{[4
]}

Kulesskiy, Evgeny ^{[1
]}

Marjomaki, Varpu S. ^{[12
]}

Julkunen, Ilkka ^{[4
]}

Nyman, Tuula A. ^{[5
,13
]}

Matikainen, Sampsa ^{[9
,10
]}

Saarela, Jani S. ^{[1
]}

Sane, Famara ^{[14
]}

Hober, Didier ^{[14
]}

Gabriel, Guelsah ^{[15
]}

De Brabander, Jef K. ^{[16
]}

Martikainen, Miika ^{[17
]}

Windisch, Marc P. ^{[11
]}

Min, Ji-Young ^{[11
]}

Bruzzone, Roberto ^{[11
,18
,19
]}

Aittokallio, Tero ^{[1
]}

Vaha-Koskela, Markus ^{[1
]}

Vapalahti, Olli ^{[20
,21
,22
]}

Pulk, Arto ^{[23
]}

Velagapudi, Vidya ^{[1
]}

Kainov, Denis E. ^{[1
,8
,11
,23
]}

机构：

[1] Univ Helsinki, FIMM, Inst Mol Med Finland, FIN-00290 Helsinki, Finland

[2] Univ Helsinki, Dept Biochem & Dev Biol, FIN-00290 Helsinki, Finland

[3] Univ Helsinki, Dept Virol, Haartmaninkatu 3, FIN-00290 Helsinki, Finland

[4] Univ Turku, Dept Virol, FIN-20520 Turku, Finland

[5] Univ Helsinki, Inst Biotechnol, Valimotie 7, Helsinki 00014, Finland

[6] Biomed Funct Genom Unit FuGU, Helsinki 00290, Helsinki, Finland

[7] Univ Tampere, Dept Virol, Tampere 33520, Finland

[8] Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7028 Trondheim, Norway

[9] Univ Helsinki, FIN-00290 Helsinki, Finland

[10] Helsinki Univ Hosp, Rheumatol, Helsinki 00290, Finland

[11] Inst Pasteur Korea, Gyeonggi Do 13488, South Korea

[12] Univ Jyvaskyla, Dept Biol & Environm Sci, Nanosci Ctr, Jyvaskyla 40500, Finland

[13] Univ Oslo, Dept Immunol, N-0424 Oslo, Norway

[14] Univ Lille, CHU Lille, Lab Virol, EA3610, F-59037 Lille, France

[15] Leibniz Inst Expt Virol, Heinrich Pette Inst, D-20251 Hamburg, Germany

[16] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[17] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, S-75237 Uppsala, Sweden

[18] Univ Hong Kong, Sch Publ Hlth, HKU Pasteur Res Pole, Hong Kong, Hong Kong, Peoples R China

[19] Inst Pasteur, Dept Cell Biol & Infect, F-75015 Paris, France

[20] Univ Helsinki, Dept Virol & Immunol, FIN-00014 Helsinki, Finland

[21] Helsinki Univ Hosp, Helsinki 00014, Finland

[22] Univ Helsinki, Dept Vet Biosci, FIN-00014 Helsinki, Finland

[23] Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia

来源：

VIRUSES-BASEL | 2017年 / 9卷 / 10期

基金：

芬兰科学院;

关键词：

apoptosis; antiviral agent; innate immunity; host response; CHRONIC LYMPHOCYTIC-LEUKEMIA; INFLUENZA-A; SYSTEMATIC ANALYSIS; GLOBAL BURDEN; CELLS; INFECTION; POTENT; SALIPHENYLHALAMIDE; TRANSCRIPTION; DISCOVERIES;

D O I：

10.3390/v9100271

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.

引用

页数：15

共 53 条

[1]

RELATIONSHIP BETWEEN VARIABLE SELECTION AND DATA AUGMENTATION AND A METHOD FOR PREDICTION [J].

ALLEN, DM .

TECHNOMETRICS, 1974, 16 (01) :125-127

[2]

Influenza virus NS1 protein binds cellular DNA to block transcription of antiviral genes [J].

Anastasina, Maria ;

Le May, Nicolas ;

Bugai, Andrii ;

Fu, Yu ;

Soderholm, Sandra ;

Gaelings, Lana ;

Ohman, Tiina ;

Tynell, Janne ;

Kyttanen, Suvi ;

Barboric, Matjaz ;

Nyman, Tuula A. ;

Matikainen, Sampsa ;

Julkunen, Ilkka ;

Butcher, Sarah J. ;

Egly, Jean-Marc ;

Kainov, Denis E. .

BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2016, 1859 (11) :1440-1448

[3]

From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors [J].

Ashkenazi, Avi ;

Fairbrother, Wayne J. ;

Leverson, Joel D. ;

Souers, Andrew J. .

NATURE REVIEWS DRUG DISCOVERY, 2017, 16 (04) :273-284

[4]

Rapid human metapneumovirus microneutralization assay based on green fluorescent protein expression [J].

Biacchesi, S ;

Skiadopoulos, MH ;

Yang, LJ ;

Murphy, BR ;

Collins, PL ;

Buchholz, UJ .

JOURNAL OF VIROLOGICAL METHODS, 2005, 128 (1-2) :192-197

[5]

Maintenance of the HIV Reservoir Is Antagonized by Selective BCL2 Inhibition [J].

Cummins, Nathan W. ;

Sainski-Nguyen, Amy M. ;

Natesampillai, Sekar ;

Aboulnasr, Fatma ;

Kaufmann, Scott ;

Badleya, Andrew D. .

JOURNAL OF VIROLOGY, 2017, 91 (11)

[6]

Prime, Shock, and Kill: Priming CD4 T Cells from HIV Patients with a BCL-2 Antagonist before HIV Reactivation Reduces HIV Reservoir Size [J].

Cummins, Nathan W. ;

Sainski, Amy M. ;

Dai, Haiming ;

Natesampillai, Sekar ;

Pang, Yuan-Ping ;

Bren, Gary D. ;

Correia, Maria Cristina Miranda de Araujo ;

Sampath, Rahul ;

Rizza, Stacey A. ;

O'Brien, Daniel ;

Yao, Joseph D. ;

Kaufmann, Scott H. ;

Badley, Andrew D. .

JOURNAL OF VIROLOGY, 2016, 90 (08) :4032-4048

[7]

Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies [J].

Delbridge, Alex R. D. ;

Grabow, Stephanie ;

Strasser, Andreas ;

Vaux, David L. .

NATURE REVIEWS CANCER, 2016, 16 (02) :99-109

[8]

Obatoclax, Saliphenylhalamide, and Gemcitabine Inhibit Influenza A Virus Infection [J].

Denisova, Oxana V. ;

Kakkola, Laura ;

Feng, Lin ;

Stenman, Jakob ;

Nagaraj, Ashwini ;

Lampe, Johanna ;

Yadav, Bhagwan ;

Aittokallio, Tero ;

Kaukinen, Pasi ;

Ahola, Tero ;

Kuivanen, Suvi ;

Vapalahti, Olli ;

Kantele, Anu ;

Tynell, Janne ;

Julkunen, Ilkka ;

Kallio-Kokko, Hannimari ;

Paavilainen, Henrik ;

Hukkanen, Veijo ;

Elliott, Richard M. ;

De Brabander, Jef K. ;

Saelens, Xavier ;

Kainov, Denis E. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (42) :35324-35332

[9]

Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities [J].

Driggers, R. W. ;

Ho, C. -Y. ;

Korhonen, E. M. ;

Kuivanen, S. ;

Jaaskelainen, A. J. ;

Smura, T. ;

Rosenberg, A. ;

Hill, D. A. ;

DeBiasi, R. L. ;

Vezina, G. ;

Timofeev, J. ;

Rodriguez, F. J. ;

Levanov, L. ;

Razak, J. ;

Iyengar, P. ;

Hennenfent, A. ;

Kennedy, R. ;

Lanciotti, R. ;

du Plessis, A. ;

Vapalahti, O. .

NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (22) :2142-2151

[10]

Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis [J].

Ebert, Gregor ;

Allison, Cody ;

Preston, Simon ;

Cooney, James ;

Toe, Jesse G. ;

Stutz, Michael D. ;

Ojaimi, Samar ;

Baschuk, Nikola ;

Nachbur, Ueli ;

Torresi, Joseph ;

Silke, John ;

Begley, C. Glenn ;

Pellegrini, Marc .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (18) :5803-5808

← 1 2 3 4 5 6 →