Platelet and HIV Interactions and Their Contribution to Non-AIDS Comorbidities

Abstract

Platelets are anucleate cytoplasmic cell fragments that circulate in the blood, where they are involved in regulating hemostasis. Beyond their normal physiologic role, platelets have emerged as versatile effectors of immune response. During an infection, cell surface receptors enable platelets to recognize viruses, resulting in their activation. Activated platelets release biologically active molecules that further trigger host immune responses to protect the body against infection. Their impact on the immune response is also associated with the recruitment of circulating leukocytes to the site of infection. They can also aggregate with leukocytes, including lymphocytes, monocytes, and neutrophils, to immobilize pathogens and prevent viral dissemination. Despite their host protective role, platelets have also been shown to be associated with various pathophysiological processes. In this review, we will summarize platelet and HIV interactions during infection. We will also highlight and discuss platelet and platelet-derived mediators, how they interact with immune cells, and the multifaceted responsibilities of platelets in HIV infection. Furthermore, we will give an overview of non-AIDS comorbidities linked to platelet dysfunction and the impact of antiretroviral therapy on platelet function.

Keywords: HIV; HIV complications; antiretroviral therapy; coagulation; inflammation; platelets; viral persistence.

Figure 1

Downstream effects of HIV-mediated platelet activation: (A) Cytokine, chemokine, and soluble factors release, such as IL-1α/β, 4, 6, 8, 10, and 13. (B) Up-regulation of P-selectin for cell–cell interaction and recruitment of leukocytes to sites of infection, as well as to dysregulated endothelium. (C) Activation of all three complement pathways (classical, lectin, and alternative) to opsonize, phagocytose, and activate inflammation. (D) Interaction with innate immune cells (monocyte, macrophage, and neutrophils).

Figure 2

HIV-1 persistence after the initial activation of platelets (A) in becoming a transient reservoir in harboring HIV-1 in vacuole compartments and OCS, allowing the spread through CD4-T cell interaction (B), phagocytosis by macrophages (C), and increasing soluble factors (TRAP6 and CD40L) to increase HIV-1-platelet interaction (D).