2′,3′-Dialdehyde of ATP, ADP, and Adenosine Inhibit HIV-1 Reverse Transcriptase and HIV-1 Replication

被引:5
作者
Schachter, Julieta [1 ,2 ]
Chaves Valadao, Ana Luiza [3 ]
Aguiar, Renato Santana [3 ]
Barreto-de-Souza, Victor [4 ]
Rossi, Atila Duque [3 ]
Arantes, Pablo Ricardo [5 ]
Verli, Hugo [5 ]
Quintana, Paula Gabriela [1 ]
Heise, Norton [1 ]
Tanuri, Amilcar [3 ]
Bou-Habib, Dumith Chequer [4 ]
Persechini, Pedro Muanis [1 ,2 ]
机构
[1] Univ Fed Rio de Janeiro, IBCCF, Polo De Xerem, RJ, Brazil
[2] INPeTAm, Conselho Nacl Desenvolvimento Cient & Tecnol, Rio De Janeiro, RJ, Brazil
[3] Univ Fed Rio de Janeiro, Inst Biol, Dept Genet, Rio De Janeiro, RJ, Brazil
[4] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Pesquisa Sobre Timo, Rio De Janeiro, RJ, Brazil
[5] Univ Fed Rio de Janeiro, Ctr Biotecnol, Rio De Janeiro, RJ, Brazil
关键词
HIV-1; macrophage; oxidized adenosine; oxidized ADP; oxidized ATP; reverse transcriptase; IMMUNODEFICIENCY-VIRUS TYPE-1; OXIDIZED ATP; MOLECULAR-MECHANISM; P2X(7) RECEPTOR; ACTIVATION; DIALDEHYDE; BINDING; INVOLVEMENT; EXPRESSION; VIRIONS;
D O I
10.2174/1570162X12666140826105824
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The 2'3'-dialdehyde of ATP or oxidized ATP (oATP) is a compound known for specifically making covalent bonds with the nucleotide-binding site of several ATP-binding enzymes and receptors. We investigated the effects of oATP and other oxidized purines on HIV-1 infection and we found that this compound inhibits HIV-1 and SIV infection by blocking early steps of virus replication. oATP, oxidized ADP (oADP), and oxidized Adenosine (oADO) impact the natural activity of endogenous reverse transcriptase enzyme (RT) in cell free virus particles and are able to inhibit viral replication in different cell types when added to the cell cultures either before or after infection. We used UFLC-UV to show that both oADO and oATP can be detected in the cell after being added in the extracellular medium. oATP also suppresses RT activity and replication of the HIV-1 resistant variants M184V and T215Y. We conclude that oATP, oADP and oADO display anti HIV-1 activity that is at in least in part due to inhibitory activity on HIV-1 RT.
引用
收藏
页码:347 / 358
页数:12
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