Work

High-throughput single-cell transcriptome analysis of immune cells from HIV-1 infected individuals before and after therapy

Year: 2017

Type: article

Abstract: Background: Beside hemostasis, human platelets carry important immunological functions by interacting with immune cells.Furthermore, platelets interact with infectious pathogens and internalize HIV in vitro.Here, we investigated whether platelets from HIV-infected patients under Combined Antiretroviral Therapy (cART) carry infectious HIV and how it correlates with patient immunological status.Methods: Infectious HIV content in platelets was assessed by PCR, Flow-FISH, confocal and electron microscopy, quantitative flow cytometry and infection-reporter cells using platelet-rich-plasma (PRP) from 75 cART-treated patients.Human primary macrophages were co-cultured with PRP without or with the platelet activation-blocker Abciximab to assess capacity of platelet-containing HIV to transfer and propagate infection.The presence of HIV in platelets was correlated with patient clinical status.Results: Platelets from cART-treated patients with detectable but also undetectable viral loads enclose infectious viruses as detected consistently by viral RNA, p24 expression, and localization within platelet internal compartment.Functionally, platelet sheltering HIV can propagate productive infection to macrophages in-vitro.Blocking platelet activation with the therapeutical agent Abciximab prevents this transfer.The occurrence of HIV-containing platelets is independent platelet numbers whereas it strongly correlates with sustain low blood CD4+T-cell counts (<350 cells/microL in a 3 years survey) and nadir (<200 cells/ml).Accordingly, 65.2% of patients sheltering HIV in platelets do not respond immunologically to cARTand fail to restore a proper immune status over 18 months with a >20-fold higher likelihood than patients without HIV in platelets (OR:21.3,95%CI:4.4-103.1,p<0.001).Conclusions: This study not only sheds new light on the biology of HIV pathogenesis, describing an alternative pathway for viral dissemination in which platelets act as carriers of infectious viruses and as new players in cell-to-cell HIV transmission, but also suggests new diagnostic and therapeutic perspectives to improve immunological recovery in cART-treated patients.

Source: Journal of Virus Eradication

DOI: 10.1016/s2055-6640(20)30548-3