Platelet activation suppresses HIV-1 infection of T cells

Abstract

BackgroundPlatelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear.ResultsWe found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity.ConclusionsRelease of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.

Platelets directly regulate DNA damage and division ofStaphylococcus aureus

“…Human PLTderived b-defensin could significantly impair the growth of clinical strains of S. aureus and induce robust neutrophil extracellular trap formation by targeting polymorphonuclear leukocytes (5). CXCL4, the most abundant PLT kinocidin, is released during HIV-1 infection in T cells in vitro, and CCL5, a major HIV suppressive factor, is also involved in this process (19,30). TGF-b1, which was secreted by PLTs in our coculture system, was markedly down-regulated.…”

“…In addition, the nucleotidebinding oligomerization domain-like receptor 2 (15), an intracellular innate immune recognition receptor, can recognize the gram-positive bacteria cell wall dipeptide, formyl peptide receptor, and apoptosis-related FAS pathway surface receptors (16,17). Furthermore, proteins that are secreted by PLTs after exposure to different stimuli, such as chemokine (C-X-C motif) ligand 4 (CXCL4)/PLT factor 4, C-C motif chemokine ligand 5 (CCL5)/RANTES, human defensins, and thymosin b4, have been demonstrated to have structures that are similar to those of antimicrobial peptides (5,(18)(19)(20)(21). These PLT transfusion characteristics thus imply that it may directly inhibit bacterial growth.…”

Transforming growth factor-β1-mediated cardiac fibrosis

“…1B), plasma levels of TGF-β are increased ~2-fold, and in advancing HIV disease a further rise in TGF-β levels was observed [32,33]. In our opinion this is a consequence of platelet activation via three possible mechanisms: binding of viral envelope to platelet DC-SIGN [34]; cytokine stimulation involving IL-6 and IL-8 [35]; and monocyte tissue factor (TF)-mediated thrombin generation [36]. All of these processes could result in platelet activation and TGF-β1 release.…”

Revisiting a quarter of a century of simian immunodeficiency virus (SIV)-associated cardiovascular diseases at the German Primate Center

“…The interaction between virus and platelets differs in SIV and HIV infection and may explain the diverging results of this study compared to studies in humans. For instance, it has been reported that platelets can secrete soluble factors like CXCL4 that inhibit HIV-1 but not HIV-2 and SIV replication in lymphocytes (Solomon et al, 2013). However, the association between the observed endocarditis and TCP is striking and deserves further investigation.…”