A Zika virus primary isolate induces neuroinflammation, compromises the blood‐brain barrier and upregulates CXCL12 in adult macaques

Panganiban, Antonito T.; Blair, Robert V; Hattler, Julian B.; Bohannon, Diana G.; Bonaldo, Myrna C.; Schouest, Blake; Maness, Nicholas J.; Kim, Woong‐Ki

doi:10.1111/bpa.12873

Cited by 26 publications

(10 citation statements)

References 55 publications

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“…RNAemia at any other time points up to the day of necropsy was not observed in any of the pregnant dams. This differs from the reports in pregnant macaques where prolonged or re-emergent viremia for several weeks up to 70 dpi has been widely reported [ 24 , 25 , 28 – 30 , 41 , 43 , 55 ]. While prolonged viremia (46 to 53 days) has been reported in pregnant women [ 56 – 59 ], this appears to be uncommon.…”

Section: Discussioncontrasting

confidence: 99%

See 1 more Smart Citation

Early and mid-gestation Zika virus (ZIKV) infection in the olive baboon (Papio anubis) leads to fetal CNS pathology by term gestation

Gurung

Reuter²,

Norris³

et al. 2022

PLoS Pathog

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Zika virus (ZIKV) infection in pregnancy can produce catastrophic teratogenic damage to the developing fetus including microcephaly and congenital Zika syndrome (CZS). We previously described fetal CNS pathology occurring by three weeks post-ZIKV inoculation in Olive baboons at mid-gestation, including neuroinflammation, loss of radial glia (RG), RG fibers, neuroprogenitor cells (NPCs) resulting in disrupted NPC migration. In the present study, we explored fetal brain pathologies at term gestation resulting from ZIKV exposure during either first or second trimester in the Olive baboon. In all dams, vRNA in whole blood resolved after 7 days post inoculation (dpi). One first trimester infected dam aborted at 5 dpi. All dams developed IgM and IgG response to ZIKV with ZIKV IgG detected in fetal serum. Placental pathology and inflammation were observed including disruption of syncytiotrophoblast layers, delayed villous maturation, partially or fully thrombosed vessels, calcium mineralization and fibrin deposits. In the uterus, ZIKV was detected in ¾ first trimester but not in second trimester infected dams. While ZIKV was not detected in any fetal tissue at term, all fetuses exhibited varying degrees of neuropathology. Fetal brains from ZIKV inoculated dams exhibited a range of gross brain pathologies including irregularities of the major gyri and sulci of the cerebral cortex and cerebellar pathology. Frontal cortices of ZIKV fetuses showed a general disorganization of the six-layered cortex with degree of disorganization varying among the fetuses from the two groups. Frontal cortices from ZIKV inoculation in the first but not second trimester exhibited increased microglia, and in both trimester ZIKV inoculation, increased astrocyte numbers (white matter). In the cerebellum, increased microglia were observed in fetuses from both first and second trimester inoculation. In first trimester ZIKV inoculation, decreased oligodendrocyte precursor cell populations were observed in fetal cerebellar white matter. In general, our observations are in accordance with those described in human ZIKV infected fetuses.

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Section: Discussioncontrasting

confidence: 99%

“…for several weeks up to 70 dpi has been widely reported [24,25,[28][29][30]41,43,55]. While prolonged viremia (46 to 53 days) has been reported in pregnant women [56][57][58][59], this appears to be uncommon.…”

Section: Plos Pathogensmentioning

confidence: 97%

Early and mid-gestation Zika virus (ZIKV) infection in the olive baboon (Papio anubis) leads to fetal CNS pathology by term gestation

Gurung

Reuter²,

Norris³

et al. 2022

PLoS Pathog

View full text Add to dashboard Cite

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“…Here, long-term increased levels of C-X-C motif chemokine ligand 12 (CXCL12), which is a chemokine involved in lymphocyte trafficking and neural repair, were described. Additionally, the authors observed inflammation in the perivascular space and meninges, accompanied by lymphocytic infiltrations (147). This was also reported in fetal human brains, where an infiltration of T and B cells was observed in the perivascular space during ZIKV infection (Figure 2) (113).…”

Section: Zika Virus (Zikv)supporting

confidence: 56%

CNS Macrophages and Infant Infections

et al. 2020

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The central nervous system (CNS) harbors its own immune system composed of microglia in the parenchyma and CNS-associated macrophages (CAMs) in the perivascular space, leptomeninges, dura mater, and choroid plexus. Recent advances in understanding the CNS resident immune cells gave new insights into development, maturation and function of its immune guard. Microglia and CAMs undergo essential steps of differentiation and maturation triggered by environmental factors as well as intrinsic transcriptional programs throughout embryonic and postnatal development. These shaping steps allow the macrophages to adapt to their specific physiological function as first line of defense of the CNS and its interfaces. During infancy, the CNS might be targeted by a plethora of different pathogens which can cause severe tissue damage with potentially long reaching defects. Therefore, an efficient immune response of infant CNS macrophages is required even at these early stages to clear the infections but may also lead to detrimental consequences for the developing CNS. Here, we highlight the recent knowledge of the infant CNS immune system during embryonic and postnatal infections and the consequences for the developing CNS.

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“…In order to penetrate the CNS, ZIKV must cross the BBB. ZIKV infection induces BBB disruption in the later stages of the disease ( Leda et al, 2019 ), as evidenced by fibrinogen diffusion into the CNS parenchyma ( Panganiban et al, 2020 ) and neuroinvasion of infected monocytes ( Ayala-Nunez et al, 2019 ; de Carvalho et al, 2019 ). However, during early ZIKV infection stages, the BBB remains intact.…”

Section: Introductionmentioning

confidence: 99%

Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells

et al. 2021

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Zika virus (ZIKV) infection has been associated with a series of neurological pathologies. In patients with ZIKV-induced neurological disorders, the virus is detectable in the central nervous system. Thus, ZIKV is capable of neuroinvasion, presumably through infection of the endothelial cells that constitute the blood-brain barrier (BBB). We demonstrate that susceptibility of BBB endothelial cells to ZIKV infection is modulated by the expression of tight-junction protein claudin-7 (CLDN7). Downregulation of CLDN7 reduced viral RNA yield, viral protein production, and release of infectious viral particles in several endothelial cell types, but not in epithelial cells, indicating that CLDN7 implication in viral infection is cell-type specific. The proviral activity of CLDN7 in endothelial cells is ZIKV-specific since related flaviviruses were not affected by CLDN7 downregulation. Together, our data suggest that CLDN7 facilitates ZIKV infection in endothelial cells at a post-internalization stage and prior to RNA production. Our work contributes to a better understanding of the mechanisms exploited by ZIKV to efficiently infect and replicate in endothelial cells and thus of its ability to cross the BBB.

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A Zika virus primary isolate induces neuroinflammation, compromises the blood‐brain barrier and upregulates CXCL12 in adult macaques

Cited by 26 publications

References 55 publications

Early and mid-gestation Zika virus (ZIKV) infection in the olive baboon (Papio anubis) leads to fetal CNS pathology by term gestation

Early and mid-gestation Zika virus (ZIKV) infection in the olive baboon (Papio anubis) leads to fetal CNS pathology by term gestation

CNS Macrophages and Infant Infections

Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells

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