STAT2 Limits Host Species Specificity of Human Metapneumovirus.

The host tropism of viral infection is determined by a variety of factors, from cell surface receptors to innate immune signaling. Many viruses encode proteins that interfere with host innate immune recognition in order to promote infection. is divergent between species and therefore has a role in species restriction of some viruses. To understand the role of duanyu18132 in human metapneumovirus (HMPV) infection of human and murine tissues, we first infected mice and found that HMPV could be serially passaged in but not WT, mice. We then used in vitro methods to show that HMPV inhibits expression of both and duanyu18132 in human and primate cells, but not in mouse cells. Transfection of the murine form of duanyu18132 into human cells conferred resistance to duanyu18132 inhibition. Finally, we sought to understand the in vivo role of duanyu18132 by infecting knock-in mice with HMPV, and found that mice had increased weight loss, inhibition of type I interferon signaling, and a Th2-polarized cytokine profile compared to WT mice. These results indicate that duanyu18132 is a target of HMPV in human infection, while the murine version of duanyu18132 restricts tropism of HMPV for murine cells and tissue.

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