Ectopic expression of murine CD163 enables cell-culture isolation of lactate dehydrogenase-elevating (LDV) virus 63 years after its discovery

Arteriviruses are RNA viruses related to coronaviruses but have not yet been associated with human infection. A murine arterivirus (lactate dehydrogenase-elevating virus, LDV) was first described in 1960 and quickly became a promising model for understanding immune failure due to its unique ability to persist in immunocompetent adult mice. However, inability to culture LDV in vitro ultimately limited this system. Here, we demonstrate that the macrophage marker CD163 is essential for LDV infection. Expression of the murine homolog (mCD163) in otherwise mCD163-negative cell lines from mice and nonhuman primates enables productive LDV infection, creating the first immortalized cell-culture system. We also show that mCD163-knockout mice are completely resistant to LDV infection. These findings advance LDV as a model of arterivirus infection viral persistence and add to a growing body of literature suggesting that CD163 utilization is a broad feature of arteriviruses.