Uptake of Influenza Virus By Platelets Occurs Via Phagocytosis

Background: Influenza virus infection often leads to thrombocytopenia in humans with sometimes life-threatening bleeding symptoms. We have recently shown uptake of influenza A/H1N1 virus by human platelets in vitro and in vivo in our ferret infection model. Although uptake of influenza virus had no effect on expression of glycoproteins (GP) 1ba, GPIX and P-selectin, or the aggregation function, the mechanism of this uptake remains unclear.

Methods: Viral uptake was studied by incubation of human platelets with fluorescent-labelled influenza A virus (A/PR/8/34-FITC) in ratio of about 1:300. Uptake of the virus was then studied by flow cytometry, after 1, 5, 10, 20, 30 and 60 minutes of incubation. To study the role of surface glycosylation platelets were treated with neuraminidase prior to virus incubation. Finally, transmission electron microscopy was performed to construct 3D images of virus-containing platelets.

Results: Influenza A virus is taken up rapidly by platelets in vitro with an average velocity of 5-10 virus particles per minute. By electron microscopy we observed platelets with virus containing vacuoles, suggesting that platelets had phagocytosed the virus. The process could be blocked by removal of the sialic acids.

Conclusion: Our study shows that platelets take up influenza virus via surface sialic acid and form vacuoles with influenza virus. This finding proves phagocytosis as mechanism of viral uptake. This function of platelets may play an important role in the occurrence of thrombocytopenia during influenza infection and may be part of the host innate response mechanism.