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    AIDS: Infectious virus hidden in platelets of treated, aviremic but immunologically failing patients

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    A study of the Morgane Bomsel team

    Infectious HIV hidden in platelets of treated, aviremic but immunologically failing patients

    A study published in the journal Science Translational Medicine shows that platelets of human immunodeficiency virus (HIV) patients harbor infectious HIV, despite effective combined antiviral therapy that suppresses viral load in the blood. In these patients, the presence of HIV in platelets is strongly correlated with the failure to restore T-CD4+ immune response. Researchers show in vitro that platelets can spread the infectious virus to macrophages, cellular reservoirs of the virus, establishing an alternative pathway to fuel HIV into this type of reservoir.

     

    The role of platelets in hemostasis is well known, but recently they have been assigned other functions. Thus, platelets interact with pathogens, bacterial or viral. It had recently been shown in vitro that platelets captured HIV. Researchers demonstrate the presence of infectious HIV in isolated platelets of HIV-infected patients, despite successful viral suppression through combined antiretroviral therapy (cART).

    Among patients with cART that suppresses viral load, 20-30% fail to restore a proper number of CD4+ T lymphocytes after at least 12 months of treatment (so-called patients in failure). The researchers compared the immunological status of patients with or without virus in their platelets and showed that the presence of infectious HIV in patients’ platelets is strongly correlated with immunological failure. 

     

     

    3D reconstruction of HIV-containing platelet images. The platelets are sectioned in their middle and the yellow dots surround the section plan limit. Platelet surface and internal membranes are green (labeled by anti-CD41 antibodies), the red virus are located inside the platelet (labeled by anti-p24 antibodies).  © Morgane Bomsel and Fernando Real

     

     

     

    The platelets are derived from the marrow megakaryocytes. Researchers also found that the megakaryocytes of patients with immunological failure were infected with HIV, which would explain that the derived platelets contain virus. On the other hand, since platelets end their lives by being phagocytozed by macrophages, the transmission of infectious HIV from platelets to tissue macrophages was tested in vitro. Platelets of HIV patients can indeed spread in vitro infection to macrophages in a cell-to-cell transmission mechanism. This process that can be inhibited by blocking platelet-macrophage interaction with the anti-platelet therapeutic agent Abciximab. 

     

    In conclusion, this study highlights HIV pathophysiology by describing another pathway of viral dissemination in which platelets play the role of transient carriers of infectious viruses to infect tissue macrophages. The presence of HIV-containing platelets characterizes immunological failure in HIV-infected patients treated with antiretroviral drugs. It is a potential target for the design of effective therapeutic strategies against immunological failure for which no treatments are yet available.

     

    This study has been financed by ANRS and Sidaction.

     

    Reference

    Platelets from HIV-infected individuals on antiretroviral drug therapy with poor CD4+ T cell recovery can harbor replication-competent HIV despite viral suppression. F. Real, C. Capron, A. Sennepin, R. Arrigucci, A. Zhu, G. Sannier, J. Zheng, L. Xu, J-M. Massé, S. Greffe, M. Cazabat, M. Donoso, P. Delobel, J. Izopet, E. Eugenin, M. L. Gennaro, E. Rouveix, E. Cramer Bordé, and M. Bomsel. Science Translational Medicine, 10.1126/scitranslmed.aat6263

     

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