# Platelet-like particles released from Ebola virus-infected megakaryocytic cells behave like virus-like particles

## TL;DR

Ebola virus can cause platelet-like particles to carry viral components, which may help the virus spread in the body and cause disease.

## Contribution

Ebola virus-infected megakaryocytes release platelet-like particles containing viral proteins and genetic material that can produce new virus.

## Key findings

- Platelet-like particles from infected cells contain EBOV proteins and genetic material.
- Viral mRNA and genome RNA are synthesized in these particles, enabling virus production in recipient cells.
- The viral glycoprotein on PLPs helps them enter other cells.

## Abstract

Ebola virus (EBOV) is likely a zoonotic and re-emerging virus that causes severe outbreaks of Ebola virus disease. The virus spreads to various tissues during the late stage of infection and has been detected in immune-privileged sites of survivors. However, the mechanism of how EBOV disseminates throughout the body is not completely elucidated. In this study, by using a biologically contained EBOVΔVP30 system, we demonstrate that a megakaryocytic-like MEG-01 cell line that stably expresses VP30 (MEG-01 VP30 cells) is susceptible to EBOVΔVP30 infection and that MEG-01 VP30 cells exposed to EBOVΔVP30 produce platelet-like particles (PLPs) that contain EBOV proteins and viral genetic material. We further found that the viral envelope glycoprotein is expressed on the surface of the produced PLPs and contributes to PLP internalization into recipient cells. In addition, viral mRNA and genome RNA are actively synthesized in these PLPs, which may lead to progeny EBOV production from recipient cells that internalize the PLPs. Taken together, our data provide new insights into the potential role of platelets in the widespread dissemination of EBOV and the pathogenesis of Ebola virus disease.

At the late stage of Ebola virus (EBOV) disease, the virus spreads to various tissues, including immune-privileged sites such as the brain, eyes, testes, and bone marrow. Even after recovery, some survivors experience relapses, and transmission of virus through breast milk or semen may occur. While EBOV is thought to disseminate throughout the body via the bloodstream or lymphatic system and through interaction with nearby cells, growing evidence shows that platelets act as important immune mediators. Platelets not only communicate with innate immune cells and endothelial cells but also interact with pathogens, including viruses. These observations led us to ask whether platelets could act as carriers of viral components (i.e., viral proteins, mRNA, and genomic RNA) capable of supporting further virus production. Using a biologically contained EBOVΔVP30 system, we show that megakaryocytes, the cells that produce platelets, can release platelet-like particles (PLPs) that contain EBOV proteins and genetic material after exposure to EBOVΔVP30. Furthermore, within these PLPs, viral mRNA and genomic RNA are actively synthesized, which can drive active progeny virus production in recipient cells that internalize them. Our study reveals a potential role for platelets during EBOV infection.