Targeting the CCL2/CCR2 Axis in HIV-1 Infection and Ischemic Stroke

Abstract

HIV-associated comorbidities, including cardiovascular and cerebrovascular events, are frequent diseases in people living with HIV. Notably, the prevalence of ischemic stroke is 3× higher in people living with HIV than in noninfected individuals, making it one of the most significant cerebrovascular events in people living with HIV. Despite this close association, the mechanisms involved in the enhanced incidence of ischemic stroke in HIV infection remain poorly understood. A chemokine CCL2, acting via its receptor CCR2, is a prominent chemoattractant involved in the recruitment of CD4+T cells and monocytes/macrophages, which are primary targets for HIV infection. Due to its role in directing leukocyte migration into the brain and enhancing blood-brain barrier permeability, CCL2 is also a critical mediator of neuroinflammation after brain damage, such as ischemic stroke. In this review, we examine the role of the CCL2/CCR2 signaling pathway in HIV infection, its influence on the progression of ischemic stroke outcome and recovery, and propose the CCL2/CCR2 axis as a possible therapeutic target in people living with HIV.