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Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System.

ABSTRACT: Zika virus (ZIKV) has been defined as a teratogenic pathogen behind the increased number of cases of microcephaly in French Polynesia, Brazil, Puerto Rico, and other South American countries. Experimental studies using animal models have achieved tremendous insight into understanding the viral pathogenesis, transmission, teratogenic mechanisms, and virus-host interactions. However, the animals used in published investigations are mostly interferon (IFN)-compromised, either genetically or via antibody treatment. Herein, we studied ZIKV infection in IFN-competent mice using African (MR766) and Asian strains (PRVABC59 and SZ-WIV01). After testing four different species of mice, we found that BALB/c neonatal mice were resistant to ZIKV infection, that Kunming, ICR and C57BL/6 neonatal mice were fatally susceptible to ZIKV infection, and that the fatality of C57BL/6 neonates from 1 to 3 days old were in a viral dose-dependent manner. The size and weight of the brain were significantly reduced, and the ZIKV-infected mice showed neuronal symptoms such as hind-limb paralysis, tremor, and poor balance during walking. Pathologic and immunofluorescent experiments revealed that ZIKV infected different areas of the central nervous system (CNS) including gray matter, hippocampus, cerebral cortex, and spinal cord, but not olfactory bulb. Interestingly, ZIKV replicated in multiple organs and resulted in pathogenesis in liver and testis, implying that ZIKV infection may engender a high health risk in neonates by postnatal infection. In summary, we investigated ZIKV pathogenesis using an animal model that is not IFN-compromised.

SUBMITTER: Li S

PROVIDER: S-EPMC5795462 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System.

Li Shuxuan S Armstrong Najealicka N Zhao Huan H Hou Wangheng W Liu Jian J Chen Chunye C Wan Junkai J Wang Wei W Zhong Chunlian C Liu Che C Zhu Hua H Xia Ningshao N Cheng Tong T Tang Qiyi Q

Viruses 20180122 1

Zika virus (ZIKV) has been defined as a teratogenic pathogen behind the increased number of cases of microcephaly in French Polynesia, Brazil, Puerto Rico, and other South American countries. Experimental studies using animal models have achieved tremendous insight into understanding the viral pathogenesis, transmission, teratogenic mechanisms, and virus-host interactions. However, the animals used in published investigations are mostly interferon (IFN)-compromised, either genetically or via ant ...[more]

PMID: 29361773

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Project description:Osteomyelitis (OM), or inflammation of bone tissue, occurs most frequently as a result of bacterial infection and severely perturbs bone structure. OM is predominantly caused by Staphylococcus aureus, and even with proper treatment, OM has a high rate of recurrence and chronicity. While S. aureus has been shown to infect osteoblasts, it remains unclear whether osteoclasts (OCs) are also a target of intracellular infection. Here, we demonstrate the ability of S. aureus to intracellularly infect and divide within OCs. OCs were differentiated from bone marrow macrophages (BMMs) by exposure to receptor activator of nuclear factor kappa-B ligand (RANKL). By utilizing an intracellular survival assay and flow cytometry, we found that at 18?h postinfection the intracellular burden of S. aureus increased dramatically in cells with at least 2?days of RANKL exposure, while the bacterial burden decreased in BMMs. To further explore the signals downstream of RANKL, we manipulated factors controlling OC differentiation, NFATc1 and alternative NF-?B, and found that intracellular bacterial growth correlates with NFATc1 levels in RANKL-treated cells. Confocal and time-lapse microscopy in mature OCs showed a range of intracellular infection that correlated inversely with S. aureus-phagolysosome colocalization. The propensity of OCs to become infected, paired with their diminished bactericidal capacity compared to BMMs, could promote OM progression by allowing S. aureus to evade initial immune regulation and proliferate at the periphery of lesions where OCs are most abundant.IMPORTANCE The inflammation of bone tissue is called osteomyelitis, and most cases are caused by an infection with the bacterium Staphylococcus aureus To date, the bone-building cells, osteoblasts, have been implicated in the progression of these infections, but not much is known about how the bone-resorbing cells, osteoclasts, participate. In this study, we show that S. aureus can infect osteoclasts and proliferate inside these cells, whereas bone-residing macrophages, immune cells related to osteoclasts, destroy the bacteria. These findings elucidate a unique role for osteoclasts to harbor bacteria during infection, providing a possible mechanism by which bacteria could evade destruction by the immune system.

Dataset Information

Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System.

Publications

Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System.

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