Publicação
Targeting membrane proteins of latently infected CD4+T cells providing a starting point to the eradication of HIV-1
| Resumo: | AIDS is characterized by an immunodeficiency developed due to an infectious disease caused by a world spread virus, the HIV‐1. Infection with this virus culminates invariably in the death of the infected individual due to opportunistic infections that find a way into the organism. Today, HIV‐1 is fought against with therapies based in antiretroviral drugs that, although efficient and able to stop or difficult the viral infectious cycle, do not provide a real cure for AIDS, this is, HIV‐1 infection is still considered a chronic and fatal condition. The incapacity of such therapies to eradicate HIV‐1 infection is in part due to the existence of viral reservoirs like the CD4+ T cells population which are responsible for maintaining the HIV‐1 in a latent state inside the cell, protecting it from the host immune system and administered drugs, waiting for some trigger capable to reactivate it. This project was born from the possibility to achieve a sterilizing cure upon finding that specific trigger, enabling the depletion of such reservoirs and subjugating the reactivated HIV‐1 to the effects of the antiretroviral drugs. For this, we traced and objective in selecting antibodies through a run of the mill technology, the phage display technique, against unknown membrane determinants of the latently infected cells searching for agonist antibodies capable of reactivating the latent HIV‐1 and possibly, bringing us one step closer to a cure for AIDS. scFv of human origin were selected against J‐Lat 10.6 and their agonist capacity in causing a phenotypic modification was evaluated resorting to flow cytometry. The work here presented permitted us to identify four promising scFv with agonist HIV‐1 latent reactivation capacities against J‐Lat 10.6 cells and, additionally demonstrated the possibility for our simple approach to be an alternative methodology to the lentiviral agonist selection method developed by Hongkai Zhang and associates. |
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| Autores principais: | Gonçalves, Vasco Miguel Reis |
| Assunto: | HIV‐1 Latency AIDS sterilizing cure Agonist antibodies scFv Phage display Teses de mestrado - 2014 |
| Ano: | 2014 |
| 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: | AIDS is characterized by an immunodeficiency developed due to an infectious disease caused by a world spread virus, the HIV‐1. Infection with this virus culminates invariably in the death of the infected individual due to opportunistic infections that find a way into the organism. Today, HIV‐1 is fought against with therapies based in antiretroviral drugs that, although efficient and able to stop or difficult the viral infectious cycle, do not provide a real cure for AIDS, this is, HIV‐1 infection is still considered a chronic and fatal condition. The incapacity of such therapies to eradicate HIV‐1 infection is in part due to the existence of viral reservoirs like the CD4+ T cells population which are responsible for maintaining the HIV‐1 in a latent state inside the cell, protecting it from the host immune system and administered drugs, waiting for some trigger capable to reactivate it. This project was born from the possibility to achieve a sterilizing cure upon finding that specific trigger, enabling the depletion of such reservoirs and subjugating the reactivated HIV‐1 to the effects of the antiretroviral drugs. For this, we traced and objective in selecting antibodies through a run of the mill technology, the phage display technique, against unknown membrane determinants of the latently infected cells searching for agonist antibodies capable of reactivating the latent HIV‐1 and possibly, bringing us one step closer to a cure for AIDS. scFv of human origin were selected against J‐Lat 10.6 and their agonist capacity in causing a phenotypic modification was evaluated resorting to flow cytometry. The work here presented permitted us to identify four promising scFv with agonist HIV‐1 latent reactivation capacities against J‐Lat 10.6 cells and, additionally demonstrated the possibility for our simple approach to be an alternative methodology to the lentiviral agonist selection method developed by Hongkai Zhang and associates. |
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