Simpson Sydney R, Singh Meera V, Dewhurst Stephen, Schifitto Giovanni, Maggirwar Sanjay B
Department of Microbiology and Immunology and.
Department of Neurology, University of Rochester Medical Center, Rochester, NY; and.
Blood Adv. 2020 Sep 22;4(18):4512-4521. doi: 10.1182/bloodadvances.2020002420.
Platelets were recently found to harbor infectious HIV virions in infected individuals who are on antiretroviral treatment with poor CD4+ T-cell recovery. In this study, we screened platelets from recently infected individuals, before and after antiretroviral therapy, for the presence of virus and examined platelet activation, as well as CD4+ T-cell recovery. This was followed by in vitro studies assessing platelet-CD4+ T-cell complex formation as a contributing factor to viral transmission. HIV+ platelets were detected in 10 of 10 acutely infected individuals with no prior history of antiretroviral therapy. The percentage of HIV+ platelets dropped significantly after 3 months of antiretroviral therapy in all of the study participants. These individuals also demonstrated significant recovery of CD4+ T cells. Interestingly, the percentage of HIV+ platelets correlated positively with viral load but not with CD4+ T-cell count. Furthermore, we found that platelet activation with soluble CD40L or thrombin receptor activator peptide 6 (TRAP6) increased platelet-virus interactions in vitro. TRAP6-mediated interactions were reduced by platelet antagonists, aspirin, and R406. We demonstrated that platelets transmit the virus to CD4+ T cells, and this transinfection was abolished by inhibiting platelet-T-cell complex formation via exposure to an anti-CD62P antibody. Additionally, treatment with TRAP6 significantly increased the transinfection, which was also inhibited by aspirin and R206. These results reveal that platelets have the potential to promote HIV viral spread during the acute stage of infection, by harboring infectious virus transmitting infection to susceptible CD4+ T cells through complex formation.
最近发现，在接受抗逆转录病毒治疗但CD4+ T细胞恢复不佳的感染个体中，血小板携带有感染性的HIV病毒颗粒。在本研究中，我们对近期感染个体在抗逆转录病毒治疗前后的血小板进行病毒筛查，并检测血小板活化情况以及CD4+ T细胞的恢复情况。随后进行体外研究，评估血小板-CD4+ T细胞复合物的形成作为病毒传播的一个促成因素。在10例既往无抗逆转录病毒治疗史的急性感染个体中，有10例检测到HIV阳性血小板。在所有研究参与者中，抗逆转录病毒治疗3个月后，HIV阳性血小板的百分比显著下降。这些个体的CD4+ T细胞也有显著恢复。有趣的是，HIV阳性血小板的百分比与病毒载量呈正相关，但与CD4+ T细胞计数无关。此外，我们发现用可溶性CD40L或凝血酶受体激活肽6（TRAP6）激活血小板可增加体外血小板与病毒的相互作用。血小板拮抗剂、阿司匹林和R406可减少TRAP6介导的相互作用。我们证明血小板可将病毒传播给CD4+ T细胞，通过暴露于抗CD62P抗体抑制血小板-T细胞复合物的形成可消除这种转染。此外，用TRAP6处理显著增加了转染，阿司匹林和R206也可抑制这种转染。这些结果表明，在感染急性期，血小板有可能通过携带感染性病毒并通过复合物形成将感染传播给易感的CD4+ T细胞，从而促进HIV病毒传播。
