Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension


People living with HIV and who receive antiretroviral therapy have a significantly improved lifespan, compared to the early days without therapy. Unfortunately, persisting viral replication in the lungs sustains chronic inflammation, which may cause pulmonary vascular dysfunction and ultimate life-threatening Pulmonary Hypertension (PH). The mechanisms involved in the progression of HIV and PH remain unclear. The study of HIV-PH is limited due to the lack of tractable animal models that recapitulate infection and pathobiological aspects of PH. On one hand, mice with humanized immune systems (hu-mice) are highly relevant to HIV research but their suitability for HIV-PH research deserves investigation. On another hand, the Hypoxia-Sugen is a well-established model for experimental PH that combines hypoxia with the VEGF antagonist SU5416. To test the suitability of hu-mice, we combined HIV with either SU5416 or hypoxia. Using right heart catheterization, we found that combining HIV+SU5416 exacerbated PH. HIV infection increases human pro-inflammatory cytokines in the lungs, compared to uninfected mice. Histopathological examinations showed pulmonary vascular inflammation with arterial muscularization in HIV-PH. We also found an increase in endothelial-monocyte activating polypeptide II (EMAP II) when combining HIV+SU5416. Therefore, combinations of HIV with SU5416 or hypoxia recapitulate PH in hu-mice, creating well-suited models for infectious mechanistic pulmonary vascular research in small animals.


© 2022 Rodriguez-Irizarry, Schneider, Ahle, Smith, Suarez-Martinez, Salazar, McDaniel Mims, Rasha, Moussa, Moustaïd-Moussa, Pruitt, Fonseca, Henriquez, Clauss, Grisham and Almodovar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.


HIV, HIV-Associated Pulmonary Hypertension, HIV-PH, EMAP II, Hypoxia, SU5416, Humanized Mice


Rodriguez-Irizarry VJ, Schneider AC, Ahle D, Smith JM, Suarez-Martinez EB, Salazar EA, McDaniel Mims B, Rasha F, Moussa H, Moustaïd-Moussa N, Pruitt K, Fonseca M, Henriquez M, Clauss MA, Grisham MB and Almodovar S (2022) Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension. Front. Immunol. 13:936164. doi: 10.3389/fimmu.2022.936164