Neurocognitive impact of Zika virus infection in adult rhesus macaques

Hsu, Denise C.; Chumpolkulwong, Kesara; Corley, Michael J.; Hunsawong, Taweewun; Inthawong, Dutsadee; Schuetz, Alexandra; Im-Erbsin, Rawiwan; Silsorn, Decha; Nadee, Panupat; Sopanaporn, Jumpol; Phuang-Ngern, Yuwadee; Klungthong, Chonticha; Reed, Matthew; Fernandez, Stefan; Ndhlovu, Lishomwa C.; Paul, Robert; Lugo‐Roman, Luis A.; Michael, Nelson L.; Modjarrad, Kayvon; Vasan, Sandhya

doi:10.1186/s12974-022-02402-4

Cited by 13 publications

(10 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, adult mice that were neonatally infected by ZIKV showed increased susceptibility to chemically induced seizures, neurodegeneration, and brain calcifications, which may be related to early TNF‐α‐mediated neuroinflammation (Nem de Oliveira Souza et al, 2018). The role of neuroinflammation in neurocognitive impairment has also been described in adult rhesus macaques infected with ZIKV (Hsu et al, 2022).…”

Section: Zikv Infection and Potential Neurological Complications Rela...mentioning

confidence: 99%

The role of glial cells in Zika virus‐induced neurodegeneration

Quincozes‐Santos

Bobermin

Costa

et al. 2023

Glia

View full text Add to dashboard Cite

Zika virus (ZIKV) is a strongly neurotropic flavivirus whose infection has been associated with microcephaly in neonates. However, clinical and experimental evidence indicate that ZIKV also affects the adult nervous system. In this regard, in vitro and in vivo studies have shown the ability of ZIKV to infect glial cells. In the central nervous system (CNS), glial cells are represented by astrocytes, microglia, and oligodendrocytes. In contrast, the peripheral nervous system (PNS) constitutes a highly heterogeneous group of cells (Schwann cells, satellite glial cells, and enteric glial cells) spread through the body. These cells are critical in both physiological and pathological conditions; as such, ZIKV-induced glial dysfunctions can be associated with the development and progression of neurological complications, including those related to the adult and aging brain. This review will address the effects of ZIKV infection on CNS and PNS glial cells, focusing on cellular and molecular mechanisms, including changes in the inflammatory response, oxidative stress, mitochondrial dysfunction, Ca 2+ and glutamate homeostasis, neural metabolism, and neuron-glia communication. Of note, preventive and therapeutic strategies that focus on glial cells may emerge to delay and/or prevent the development of ZIKV-induced neurodegeneration and its consequences.André Quincozes-Santos and Larissa Daniele Bobermin contributed equally to this work.

show abstract

Section: Zikv Infection and Potential Neurological Complications Rela...mentioning

confidence: 99%

The role of glial cells in Zika virus‐induced neurodegeneration

Quincozes‐Santos

Bobermin

Costa

et al. 2023

Glia

View full text Add to dashboard Cite

show abstract

“…Identification and characterization of equivalent human monoclonal antibodies would be highly informative. Further animal protection studies would inform the protective capacity of these mAbs, including neurocognitive protection, 60 or blocking placental transmission in both naive or DENV-experienced backgrounds. 61 , 62 …”

Section: Discussionmentioning

confidence: 99%

Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

Sankhala,

Dussupt,

Donofrio

et al. 2023

Cell Reports

Self Cite

View full text Add to dashboard Cite

“…a, b, d Representative single confocal sections and the corresponding merge images are shown. Scale bars = 10 µm are often observed after the resolution of infection [10][11][12][13]16]. A role for active pro-inflammatory microglia in inducing pTau has been shown [57].…”

Section: Discussionmentioning

confidence: 99%

“…Until recently, microcephaly in newborns was the most abundantly described ZIKV-induced neuropathology and thus fetal neural progenitor cells rather than mature neurons have been considered as the main target of infection. However, there is now evidence in humans [8][9][10], macaques [11,12] and mice [13,14] that delayed neuropathies of the central nervous system (CNS), associated with cognitive disorders, can develop following neonatal and adult ZIKV infections.…”

Section: Introductionmentioning

confidence: 99%

Zika virus infection of mature neurons from immunocompetent mice generates a disease-associated microglia and a tauopathy-like phenotype in link with a delayed interferon beta response

Manet

Mansuroglu

Conquet

et al. 2022

J Neuroinflammation

View full text Add to dashboard Cite

Background Zika virus (ZIKV) infection at postnatal or adult age can lead to neurological disorders associated with cognitive defects. Yet, how mature neurons respond to ZIKV remains substantially unexplored. Methods The impact of ZIKV infection on mature neurons and microglia was analyzed at the molecular and cellular levels, in vitro using immunocompetent primary cultured neurons and microglia, and in vivo in the brain of adult immunocompetent mice following intracranial ZIKV inoculation. We have used C57BL/6 and the genetically diverse Collaborative Cross mouse strains, displaying a broad range of susceptibility to ZIKV infection, to question the correlation between the effects induced by ZIKV infection on neurons and microglia and the in vivo susceptibility to ZIKV. Results As a result of a delayed induction of interferon beta (IFNB) expression and response, infected neurons displayed an inability to stop ZIKV replication, a trait that was further increased in neurons from susceptible mice. Alongside with an enhanced expression of ZIKV RNA, we observed in vivo, in the brain of susceptible mice, an increased level of active Iba1-expressing microglial cells occasionally engulfing neurons and displaying a gene expression profile close to the molecular signature of disease-associated microglia (DAM). In vivo as well as in vitro, only neurons and not microglial cells were identified as infected, raising the question of the mechanisms underlying microglia activation following brain ZIKV infection. Treatment of primary cultured microglia with conditioned media from ZIKV-infected neurons demonstrated that type-I interferons (IFNs-I) secreted by neurons late after infection activate non-infected microglial cells. In addition, ZIKV infection induced pathological phosphorylation of Tau (pTau) protein, a hallmark of neurodegenerative tauopathies, in vitro and in vivo with clusters of neurons displaying pTau surrounded by active microglial cells. Conclusions We show that ZIKV-infected mature neurons display an inability to stop viral replication in link with a delayed IFNB expression and response, while signaling microglia for activation through IFNs-I secreted at late times post-infection. In the brain of ZIKV-infected susceptible mice, uninfected microglial cells adopt an active morphology and a DAM expression profile, surrounding and sometimes engulfing neurons while ZIKV-infected neurons accumulate pTau, overall reflecting a tauopathy-like phenotype.

show abstract

Neurocognitive impact of Zika virus infection in adult rhesus macaques

Cited by 13 publications

References 75 publications

The role of glial cells in Zika virus‐induced neurodegeneration

The role of glial cells in Zika virus‐induced neurodegeneration

Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

Zika virus infection of mature neurons from immunocompetent mice generates a disease-associated microglia and a tauopathy-like phenotype in link with a delayed interferon beta response

Contact Info

Product

Resources

About