Circulating apoB-containing lipoproteins constituted blood-borne innate immune barrier limits ZIKV dissemination and congenital infection risk

Following establishment of primary viremia, flaviviruses require prompt penetration through vascular endothelium to achieve systemic dissemination, yet most infections remain asymptomatic or self-limited. Canonical defenses, including complement and phagocyte clearance, cannot fully explain this containment, suggesting an additional blood-borne antiviral barrier. Here, we identify apoB containing lipoproteins as potent restriction factors against Zika virus (ZIKV), a devastating danger of global pregnancy. By displaying surface accessible phosphatidylserine (PS), they competitively occupy host PS receptors and block entry by viruses exploiting apoptotic mimicry, including flaviviruses, Ebola, and chikungunya virus. In vivo, increasing apoB lipoproteins enhances serum antiviral activity and limits systemic ZIKV dissemination. This barrier extends to the maternal fetal interface, where elevated maternal LDL attenuates vertical transmission and fetal abnormalities. Its efficacy is modulated by gestational fluctuations in maternal LDL level and low abundance in fetal circulating LDL. Collectively, apoB containing lipoproteins form a constitutive blood-borne innate immune barrier that restrains apoptotic-mimicry viruses during the intravascular phase, limits viral dissemination and reduces congenital infection risk. This study provides a rationale for developing diet augmentation strategy to strengthen this innate barrier in at-risk individuals.