Dysregulation of multiple inflammatory molecules in lymph node and ileum of macaques during RT-SHIV infection with or without antiretroviral therapy

Abstract

Background: Pathogenic infection with human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) is characterized by a loss of CD4+ T cells and chronic lymphocyte activation even during suppressive antiretroviral therapy (ART).

Methods: Using NanoString, expression of >100 molecules associated with inflammation or immune activation was evaluated in mesenteric lymph nodes and ileum of macaques infected with a pathogenic SIV/HIV virus, RT-SHIV, during viremia or during suppressive ART and compared to uninfected controls.

Results: Of the 105 RNA species quantified in the tissues, expression of 33 genes was altered significantly in one or both tissues during viremia but returned to normal levels during ART. However, 29 additional genes were altered in expression levels in the tissues of both viremic and ART-suppressed macaques.

Conclusions: Identification of the mechanisms of chronic inflammation in specific cells and in different tissues may help determine whether early ART initiation or novel therapies can prevent it.

Keywords: HIV; inflammation; persistence; reservoirs.