LAUSR

Significance Infection is often associated with thrombocytopenia and rapid replenishment of platelets may be important to maintain vascular homeostasis. We found that an activated form of tyrosyl-tRNA synthetase (YRSACT) mimics inflammatory stress in mice, inducing a distinct population of megakaryocytes (MKs) from myeloid/MK-biased hematopoietic stem cells bypassing the classical MK-erythroid progenitor (MEP) pathway. In mice infected by lymphocytic choriomeningitis virus, myeloid/MK progenitors and MKs were mobilized from the bone marrow into the circulation and found trapped in the lung microvasculature within fibrin containing microthrombi. These findings define the role of YRSACT in platelet generation and advance our understanding of functionally distinct alternative platelet production during viral infection.