Papel de la proteínas MRP4 y de la postaglandina E2 en la infección por el VIH

Resumen

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.