LRP8: the cellular entry receptor for yellow fever virus

Recently, our study published in Nature Microbiology identified low-density lipoprotein receptor-related protein 8 (LRP8, also known as APOER2) as a functional receptor for YFV (Fig. 1). 1 Yellow fever virus (YFV), the first human virus ever discovered, has profoundly influenced world history and remains a significant threat to global public health, with a case-fatality rate of 20%-50% and an estimated 29,000-60,000 deaths annually.2 The live-attenuated 17D vaccine, developed in the 1930s by Max Theiler through serial passage of the wild-type Asibi strain in mouse brain and chicken embryo tissues, has been administered to over 500 million people and is one of the most successful vaccines to date.[3][4][5] However, the vaccine has well-documented safety concerns, including Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) in infants and neurotropic disease (YEL-AND) in the elderly, 6,7 and no antiviral drug is currently available.Understanding how YFV enters host cells is therefore a critical step toward developing safer vaccines and effective therapeutics.