Papel de la proteínas MRP4 y de la prostaglandina E2 en la infección por el VIH
Entity
UAM. Departamento de Biología Molecular; Hospital General Universitario Gregorio MarañónDate
2011-05-05Subjects
VIH (Virus)-Tesis doctoral; Infecciones por VIH-Farmacoterapia-Tesis doctoral; Biología y Biomedicina / BiologíaNote
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 05-05-2011Abstract
The use of highly active antiretroviral therapy (HAART) in HIV treatment has
improved survival and quality of life of patients. However, the emergence of
drug-resistances, adverse effects and high cost of the therapy are some of the
problems associated with its use. Recent data suggest the study of factors and
cellular proteins as potential therapeutic targets to HIV treatment.
The multidrug resistance proteins (MRPs) form a subfamily within the ATP
binding cassette transporters that confer resistance to a variety of structurally
unrelated compounds. MRP4 has been reported to transport antiretroviral drugs
out of cells in an active process. Although the main therapeutic effects of nonsteroidal
anti-inflammatory drugs (NSAIDs) are their ability to inhibit
cyclooxygenase activity, in recent years, some pharmacological effects
independent of this action have been described, such as inhibition of the activity
of MRP4. NSAIDs can improve the antiretroviral activity of NRTIs, increasing
their intracellular concentration by blocking MRP4. This finding could have
implications for success of antiviral therapy. Interestingly, patients treated with
highly active antiretroviral therapy, who had a detectable viral load, presented a
higher expression of MRP4 than those with an undetectable viral load.
On the other hand, elevated levels of prostaglandins (PGs) are found in the
plasma of HIV-infected people. Prostaglandins (PGs) play a significant role in
many different viral infections with respect to replication and pathogenesis. Here
we investigated the role of PGs in the HIV infection cycle. Post-infection
treatment with PGE2 altered HIV infection in primary T cells by decreasing HIV
replication at post-binding step, late in the viral cycle. Interestingly, viral protein
synthesis was not affected but we found loss of progeny virus production, as well
as lower infectivity of new virions. All these effects are directly linked to the actin
dynamic and transport of viral proteins.
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"Texto de la Tesis Doctoral"
Google Scholar:Clemente Mayoral, María Isabel
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