Browsing by Author "Arora, Nitin"

Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages.
    (Cell host & microbe, 2018-11) Zimmerman, Matthew G; Quicke, Kendra M; O'Neal, Justin T; Arora, Nitin; Machiah, Deepa; Priyamvada, Lalita; Kauffman, Robert C; Register, Emery; Adekunle, Oluwaseyi; Swieboda, Dominika; Johnson, Erica L; Cordes, Sarah; Haddad, Lisa; Chakraborty, Rana; Coyne, Carolyn B; Wrammert, Jens; Suthar, Mehul S
    Zika virus (ZIKV), which emerged in regions endemic to dengue virus (DENV), is vertically transmitted and results in adverse pregnancy outcomes. Antibodies to DENV can cross-react with ZIKV, but whether these antibodies influence ZIKV vertical transmission remains unclear. Here, we find that DENV antibodies increase ZIKV infection of placental macrophages (Hofbauer cells [HCs]) from 10% to over 80% and enhance infection of human placental explants. ZIKV-anti-DENV antibody complexes increase viral binding and entry into HCs but also result in blunted type I interferon, pro-inflammatory cytokine, and antiviral responses. Additionally, ZIKV infection of HCs and human placental explants is enhanced in an immunoglobulin G subclass-dependent manner, and targeting FcRn reduces ZIKV replication in human placental explants. Collectively, these findings support a role for pre-existing DENV antibodies in enhancement of ZIKV infection of select placental cell types and indicate that pre-existing immunity to DENV should be considered when addressing ZIKV vertical transmission.
  • Thumbnail Image
    ItemOpen Access
    Gestational Stage and IFN-λ Signaling Regulate ZIKV Infection In Utero.
    (Cell host & microbe, 2017-09) Jagger, Brett W; Miner, Jonathan J; Cao, Bin; Arora, Nitin; Smith, Amber M; Kovacs, Attila; Mysorekar, Indira U; Coyne, Carolyn B; Diamond, Michael S
    Although Zika virus (ZIKV)-induced congenital disease occurs more frequently during early stages of pregnancy, its basis remains undefined. Using established type I interferon (IFN)-deficient mouse models of ZIKV transmission in utero, we found that the placenta and fetus were more susceptible to ZIKV infection at earlier gestational stages. Whereas ZIKV infection at embryonic day 6 (E6) resulted in placental insufficiency and fetal demise, infections at midstage (E9) resulted in reduced cranial dimensions, and infection later in pregnancy (E12) caused no apparent fetal disease. In addition, we found that fetuses lacking type III IFN-λ signaling had increased ZIKV replication in the placenta and fetus when infected at E12, and reciprocally, treatment of pregnant mice with IFN-λ2 reduced ZIKV infection. IFN-λ treatment analogously diminished ZIKV infection in human midgestation fetal- and maternal-derived tissue explants. Our data establish a model of gestational stage dependence of ZIKV pathogenesis and IFN-λ-mediated immunity at the maternal-fetal interface.