Publicação
Novel Strategy to Detect and Localize Latent HIV Reservoirs
| Resumo: | Over the years, the scientific eagerness to find a cure for human immunodeficiency virus (HIV) led us to, try after try, be closer to finding it. For the first time, in 1996, appears a new therapeutic strategy that consists in combinations of different antiretroviral drugs. Over the last years, the most used therapy against HIV has been combinational antiretroviral therapy (cART) although, it is not able to eradicate HIV from the host due to HIV latency. The cART works by stopping the replication cycle of HIV, but, when the virus is latent, its replication cycle is interrupted, thus making impossible for cART to fully eliminate the provirus from the host. Nowadays, the HIV/acquired immunodeficiency syndrome (AIDS) research has the goal to discover the answer to the question of the last years: what is the best method to reactivate the latent HIV? There are records of a wide range of compounds that can stimulate the HIV reactivation (latency-reversing agents – LRAs), but everyone has a disadvantage or a low efficacy in vivo. The search for a more efficient and specific non-toxic LRA has greatly increased. New strategies have emerged that consist in the combination of more potent LRAs with specific vehicles to delivery. Cell receptors have the ability to generate a response after the binding of an antigen. These receptors can be customized allowing to choose the sensing and response behaviors. With this new concept, we developed a strategy that comprehends the reactivation of latent reservoirs upon receptor recognition and the induction of T cell activation which leads to the death of the infected cell. Here, our results shown that the developed receptor is capable of sensing surface-expressed gp120 and inducing the expression of a reporter vector allowing us to detect gp120+ cells. Thus, this customized cell response is a promising method to be employed as a therapeutic strategy after future optimizations. |
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| Autores principais: | Cardoso, Miguel Gomes |
| Assunto: | HIV-1 Latency Notch receptors Reactivation T Cell engineering Tese de mestrado - 2017 |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Over the years, the scientific eagerness to find a cure for human immunodeficiency virus (HIV) led us to, try after try, be closer to finding it. For the first time, in 1996, appears a new therapeutic strategy that consists in combinations of different antiretroviral drugs. Over the last years, the most used therapy against HIV has been combinational antiretroviral therapy (cART) although, it is not able to eradicate HIV from the host due to HIV latency. The cART works by stopping the replication cycle of HIV, but, when the virus is latent, its replication cycle is interrupted, thus making impossible for cART to fully eliminate the provirus from the host. Nowadays, the HIV/acquired immunodeficiency syndrome (AIDS) research has the goal to discover the answer to the question of the last years: what is the best method to reactivate the latent HIV? There are records of a wide range of compounds that can stimulate the HIV reactivation (latency-reversing agents – LRAs), but everyone has a disadvantage or a low efficacy in vivo. The search for a more efficient and specific non-toxic LRA has greatly increased. New strategies have emerged that consist in the combination of more potent LRAs with specific vehicles to delivery. Cell receptors have the ability to generate a response after the binding of an antigen. These receptors can be customized allowing to choose the sensing and response behaviors. With this new concept, we developed a strategy that comprehends the reactivation of latent reservoirs upon receptor recognition and the induction of T cell activation which leads to the death of the infected cell. Here, our results shown that the developed receptor is capable of sensing surface-expressed gp120 and inducing the expression of a reporter vector allowing us to detect gp120+ cells. Thus, this customized cell response is a promising method to be employed as a therapeutic strategy after future optimizations. |
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