Characterization of natural killer cells from HIV+ patients and the study of epigenetic changes related to their function and phenotype

Abstract

The acquired immunodeficiency syndrome (AIDS) is considered a pandemic and is associated with leading causes of death worldwide. This infectious disease is caused by human immunodeficiency virus (HIV) and affects mainly the defense cells of the infected individual, i.e., the immune system. In this sense, several disorders related to immune cells have been reported, which increase the susceptibility of infected individuals to opportunistic infections. In HIV infection, NK cells have shown potential in the control of viral replication and in the protection of individual to opportunistic co-infections. So, multiple studies have shown dysfunctions associated with NK cells in HIV infected people like reduction of cellular cytotoxicity mechanisms and abnormal expression of cellular receptors. These changes may be related to genetic characteristics of individuals, or may result from direct and/or indirect modifications induced by the virus. Among these changes, epigenetic modifications can occur associated to transcriptional regulation and expression of some key genes of NK cell function involved in the control or susceptibility to HIV infection. Thus, the objectives of this project are to characterize the phenotype and function of NK cells from HIV infected patients and explore the relationship of these changes as a result of epigenetic modifications in genes associated to NK cell effector response. Therefore, this study will contribute in the comprehension of immune mechanisms related to HIV infection and in the search for biomarkers of the innate immune response that may be included as a new clinical parameter in determining the initiation of antiretroviral therapy (ART).