Vaccinia Virus Infection Modulates the Hematopoietic Cell Compartments in the Bone Marrow

¹ Department of Microbiology and Immunology, and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202. Walther Cancer Institute, Indianapolis, Indiana 46202.

^* To whom correspondence should be addressed. E-mail: heechang{at}umich.edu.

	Abstract

Successful proliferation and differentiation of hematopoietic progenitor cells in bone marrow (BM) is essential to generate all mature blood cell types including those involved in the immune response. Although vaccinia virus (VV) is known to induce a strong immune response, the effect of VV infection on hematopoiesis remains largely unknown. Here, we showed that in vivo VV infection results in the expansion of Lin^-Sca1⁺c-Kit⁺ (KSL) hematopoietic stem cells. The in vivo expansion of the KSL population required MyD88 that is a critical adaptor for Toll-like receptor-mediated signaling. Moreover, in BM of VV-infected mice, the population containing myeloid committed progenitor cells (CMP) was decreased due to the rapid differentiation of CMP to more mature cells. However, the CMP compartment was not affected by VV infection in the absence of MyD88. Lymphoid committed progenitor cell population (CLP) was increased regardless of MyD88 status suggesting the independent regulation of CMP and CLP compartments by VV infection. VV infection also enhanced the potential of progenitors that preferentially induces the programming of dendritic cell (DC) development toward plasmacytoid DC. Therefore, the host immune response is gearing toward anti-viral responses as early as at the precursor level upon VV infection.