Dataset Information

American Strain of Zika Virus Causes More Severe Microcephaly Than an Old Asian Strain in Neonatal Mice.

ABSTRACT: Zika virus (ZIKV) has evolved from an overlooked mosquito-borne flavivirus into a global health threat due to its astonishing causal link to microcephaly and other disorders. ZIKV has been shown to infect neuronal progenitor cells of the fetal mouse brain, which is comparable to the first-trimester human fetal brain, and result in microcephaly. However, whether there are different effects between the contemporary ZIKV strain and its ancestral strain in the neonatal mouse brain, which is comparable with the second-trimester human fetal brain, is unclear. Here we adopted a mouse model which enables us to study the postnatal effect of ZIKV infection. We show that even 100 pfu of ZIKV can replicate and infect neurons and oligodendrocytes in most parts of the brain. Compared with the ancestral strain from Cambodia (CAM/2010), infection of the ZIKV strain from Venezuela (VEN/2016) leads to much more severe microcephaly, accompanied by more neuronal cell death, abolishment of oligodendrocyte development, and a more dramatic immune response. The serious brain damage caused by VEN/2016 infection would be helpful to elucidate why the American strain resulted in severe neurovirulence in infants and will provide clinical guidance for the diagnosis and treatment of infection by different ZIKV strains.

SUBMITTER: Zhang F

PROVIDER: S-EPMC5704065 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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American Strain of Zika Virus Causes More Severe Microcephaly Than an Old Asian Strain in Neonatal Mice.

Zhang Feng F Wang Hong-Jiang HJ Wang Qin Q Liu Zhong-Yu ZY Yuan Ling L Huang Xing-Yao XY Li Guanghui G Ye Qing Q Yang Haozhen H Shi Lei L Deng Yong-Qiang YQ Qin Cheng-Feng CF Xu Zhiheng Z

EBioMedicine 20171020

Zika virus (ZIKV) has evolved from an overlooked mosquito-borne flavivirus into a global health threat due to its astonishing causal link to microcephaly and other disorders. ZIKV has been shown to infect neuronal progenitor cells of the fetal mouse brain, which is comparable to the first-trimester human fetal brain, and result in microcephaly. However, whether there are different effects between the contemporary ZIKV strain and its ancestral strain in the neonatal mouse brain, which is comparab ...[more]

PMID: 29107512

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Project description:Perineuronal nets (PNNs) form a specialized extracellular matrix that predominantly surrounds parvalbumin (PV)-expressing GABAergic inhibitory interneurons and help regulate neuronal activity. Their formation early in the postnatal period is regulated by neuronal signaling and glial activation raising concerns that part of the long-term effects ascribed to perinatal viral infections could be mediated by altered PNN formation. Previously, we developed a model of neonatal Zika virus (ZIKV) infection where mice have lifelong neurological sequelae that includes motor disfunction and reduced anxiety coupled with a persistent low-grade expression in proinflammatory markers despite resolving the acute infection. Here, we demonstrate that ZIKV infection to P1 neonatal mice results in a reduction of PNN formation during the acute disease with significant reduction in Wisteria floribunda agglutinin (WFA) staining at the peak of infection [15 days post infection (dpi)] that persisted after the symptoms resolved (30 dpi). At 60 dpi, when there is residual inflammation in the CNS, the number of WFA+ cells and the level of WFA staining as well as levels of aggrecan and brevican in the brains of convalescent mice were not different from those in uninfected controls, however, there was increased frequency of PNNs with an immature phenotype. Over time the impact of the perinatal infection became less evident and there were no clear differences in PNN morphology between the groups at 1 year post infection. Of note, the reduction in PNNs during acute ZIKV infection was not associated with decreased mRNA levels of aggrecan or brevican, but increased levels of degraded aggrecan and brevican indicating increased PNN degradation. These changes were associated with increased expression of matrix metalloproteinase 12 (MMP12) and MMP19, but not MMP9, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) or ADAMTS5. Together our findings indicate that infection at the time of PNN development interferes with PNN formation, but the nets can reform once the infection and inflammation subside.

Project description:BackgroundOur current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups.Methods and findingsWe examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.ConclusionsOur findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

Dataset Information

American Strain of Zika Virus Causes More Severe Microcephaly Than an Old Asian Strain in Neonatal Mice.

Publications

American Strain of Zika Virus Causes More Severe Microcephaly Than an Old Asian Strain in Neonatal Mice.

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