HIV‐1 Infected NSG‐BLT Humanized Mice as a Model for HIV‐Associated Lung Complications

Abstract

Human immunodeficiency virus (HIV) is an incurable and life‐threatening disease impacting over 36 million people world‐wide. Antiretroviral treatment (ART) suppresses the virus and allows many patients to live longer lives. However, even patients undergoing ART are susceptible to complications in many organ systems including the lung. HIV has been successfully linked to pulmonary complications including: tuberculosis, cytomegalovirus, Hodgkin's lymphoma, chronic obstructive pulmonary disease (COPD), and pulmonary arterial hypertension (PAH). Some of these diseases have a higher prevalence amongst patients infected with HIV. For example, in HIV patients, the incidence of PAH is 1:200, which is approximately 300‐fold higher than idiopathic PAH in the general population. Due to the limited host specificity of HIV, there are not many well‐developed animal models to study these complications. However, previous research in NOD‐Scid IL‐2 receptor γ chain knockout mice engrafted with human hematopoietic stem cells (hCD34+) and surgically implanted with human fetal thymic and liver tissue (NSG‐BLT mice) has shown disseminated HIV infection, making NSG‐BLT mice a promising in vivo model. In this study, we aimed to confirm HIV dissemination to the lungs in these mice and to examine pulmonary pathologies after an acute infection period. We infected NSG‐BLT mice with HIV for 5, 10, or 15 weeks and looked for viral RNA and pro‐viral DNA in the lungs using qPCR and nested PCR, respectively. To begin investigating possible lung pathology, we measured cytokines from lung tissue and cell‐free bronchoalveolar (BAL) fluid using an ELISA‐based protein array. Of the many proteins that were dysregulated in HIV infected mice, RAGE and IL‐25 (also known as IL‐17) are of particular interest because they have been implicated in endothelial dysfunction or vascular remodeling. This suggests a role of these proteins in HIV‐directed lung pathology in these mice. We are currently confirming the dysregulation of these genes by qPCR. In conclusion, NSG‐BLT mice constitute a useful model for studying pulmonary dissemination and pathologies during HIV infection.Support or Funding InformationNational Institutes of Health (NIH) 1R01HL125050‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.