The role of glial cells in Zika virus-induced neurodegeneration.

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, Ca2+ 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.

Differential proteomics of Zika virus (ZIKV) infection reveals molecular changes potentially involved in immune system evasion by a Brazilian strain of ZIKV.

Zika virus (ZIKV) is an arbovirus that was responsible for multiple outbreaks from 2007 to 2015. It has been linked to cases of microcephaly in Brazil in 2015, among other neurological disorders. Differences among strains might be the reason for different clinical outcomes of infection. To evaluate this hypothesis, we performed a comparative proteomic analysis of Vero cells infected with the African strain MR766 (ZIKVAFR) and the Brazilian strain 17 SM (ZIKVBR). A total of 550 proteins were identified as differentially expressed in ZIKVAFR- or ZIKVBR-infected cells compared to the control. The main findings included upregulation of immune system pathways (neutrophil degranulation and adaptive/innate immune system) and potential activation of immune-system-related pathways by ZIKVAFR (mTOR, JAK-STAT, NF-κB, and others) compared with the ZIKVBR/control. In addition, phagocytosis by macrophages and engulfment of leukocytes were activated in ZIKVAFR infection. An in vivo analysis using an immunocompetent C57BL/6N mouse model identified interstitial pneumonia with neutrophil infiltration in the lungs only in mice infected with ZIKVBR at 48 hours postinfection, with a significant amount of virus detected. Likewise, only animals infected with ZIKVBR had viral material in the cytoplasm of lung macrophages. These results suggest that activation of the immune system by ZIKVAFR infection may lead to faster viral clearance by immune cells.

Zika Virus Infection Associated with Autism Spectrum Disorder: A Case Report.

INTRODUCTION: The aim of this case was to investigate the association of the Zika virus infection in utero with the autism spectrum disorder (ASD) as clinical outcome that presented no congenital anomalies. METHODS: ASD was diagnosed in the second year of life by different child neurologists and confirmed by DSM-5 and ASQ. After that, an extensive clinical, epidemiological, and genetic evaluations were performed, with main known ASD causes ruled out. RESULTS: An extensive laboratorial search was done, with normal findings. SNP array identified no pathogenic variants. Normal neuroimaging and EEG findings were also obtained. ZIKV (Zika virus) IgG was positive, while IgM was negative. Other congenital infections were negative. The exome sequencing did not reveal any pathogenic variant in genes related to ASD. CONCLUSION: Accordingly, this report firstly associates ZIKV exposure to ASD.

ZIKAVID-Zika virus infection database: a new platform to analyze the molecular impact of Zika virus infection.

The recent outbreak of Zika virus (ZIKV) in Brazil and other countries globally demonstrated the relevance of ZIKV studies. During and after this outbreak, there was an intense increase in scientific production on ZIKV infections, especially toward alterations promoted by the infection and related to clinical outcomes. Considering this massive amount of new data, mainly thousands of genes and proteins whose expression is impacted by ZIKV infection, the ZIKA Virus Infection Database (ZIKAVID) was created. ZIKAVID is an online database that comprises all genes or proteins, and associated information, for which expression was experimentally measured and found to be altered after ZIKV infection. The database, available at https://zikavid.org, contains 16,984 entries of gene expression measurements from a total of 7348 genes. It allows users to easily perform searches for different experimental hosts (cell lines, tissues, and animal models), ZIKV strains (African, Asian, and Brazilian), and target molecules (messenger RNA [mRNA] and protein), among others, used in differential expression studies regarding ZIKV infection. In this way, the ZIKAVID will serve as an additional and important resource to improve the characterization of the molecular impact and pathogenesis associated with ZIKV infection.

Updating the application of Metarhizium anisopliae to control cattle tick Rhipicephalus microplus (Acari: Ixodidae).

The bovine tick, Rhipicephalus microplus, is the main ectoparasite of cattle and causes loss of billions of dollars worldwide in lost meat, milk, and leather production, as well as control expenses. In addition to systemically impacting the host during the parasitic act, this parasite is also an important disease vector. Traditionally, the main commercial control of the tick is achieved through application of chemical acaricides, which can leave residues in the meat and milk. Moreover, ticks can become resistant to these chemicals due to their massive and incorrect use. Many alternative methods have been tested including vaccines and natural products from plant origin. However, the efficacy of these treatments is variable and limited, especially when used alone. Arthropod-pathogenic fungi, such as Metarhizium anisopliae, are among the natural microbial agents with promising potential to be used alone or in association with other products, for example with chemical acaricides. This article discusses several aspects of bovine tick control related to the use of M. anisopliae, which is one of the most studied and viable alternative tools for effective tick control.

Proteomics of Rat Lungs Infected by Cryptococcus gattii Reveals a Potential Warburg-like Effect.

Cryptococcus gattii is the causative agent of cryptococcosis infection that can lead to pneumonia and meningitis in immunocompetent individuals. The molecular basis of the pathogenic process and impact on the host biochemistry are poorly understood and remain largely unknown. In this context, a comparative proteomic analysis was performed to investigate the response of the host during an infection caused by C. gattii. Lungs of experimentally infected rats were analyzed by shotgun proteomics to identify differentially expressed proteins induced by C. gattii clinical strain. The proteomic results were characterized using bioinformatic tools, and subsequently, the molecular findings were validated in cell culture and lungs of infected animals. A dramatic change was observed in protein expression triggered by C. gattii infection, especially related to energy metabolism. The main pathways affected include aerobic glycolysis cycle, TCA cycle, and pyrimidine and purine metabolism. Analyses in human lung fibroblast cells confirmed the altered metabolic status found in infected lungs. Thus, it is clear that C. gattii infection triggers important changes in energy metabolism leading to the activation of glycolysis and lactate accumulation in lung cells, culminating in a cancerlike metabolic status known as the Warburg effect. The results presented here provide important insights to better understand C. gattii molecular pathogenesis.

Secretomic analysis of Beauveria bassiana related to cattle tick, Rhipicephalus microplus, infection.

Beauveria bassiana is widely studied as an alternative to chemical acaricides in controlling the cattle tick Rhipicephalus microplus. Although its biocontrol efficiency has been proved in laboratory and field scales, there is a need to a better understanding of host interaction process at molecular level related to biocontrol activity. In this work, applying a proteomic technique multidimensional protein identification technology (MudPIT), the differential secretome of B. bassiana induced by the host R. microplus cuticle was evaluated. The use of the host cuticle in a culture medium, mimicking an infection condition, is an established experimental model that triggers the secretion of inducible enzymes. From a total of 236 proteins, 50 proteins were identified exclusively in infection condition, assigned to different aspects of infection like host adhesion, cuticle penetration and fungal defense, and stress. Other 32 proteins were considered up- or down-regulated. In order to get a meaningful global view of the secretome, several bioinformatic analyses were performed. Regarding molecular function classification, the highest number of proteins in the differential secretome was assigned in to hydrolase activity, enzyme class of all cuticle-degrading enzymes like lipases and proteases. These activities were also further validated through enzymatic assays. The results presented here reveal dozens of specific proteins and different processes potentially implicated in cattle tick infection improving the understanding of molecular basis of biocontrol of B. bassiana against R. microplus.

Zika Virus Infection of Human Mesenchymal Stem Cells Promotes Differential Expression of Proteins Linked to Several Neurological Diseases.

The recent microcephaly outbreak in Brazil has been associated with Zika virus (ZIKV) infection. The current understanding of damage caused by ZIKV infection is still unclear, since it has been implicated in other neurodegenerative and developmental complications. Here, the differential proteome analysis of human mesenchymal stem cells (hMSC) infected with a Brazilian strain of ZIKV was identified by shotgun proteomics (MudPIT). Our results indicate that ZIKV induces a potential reprogramming of the metabolic machinery in nucleotide metabolism, changes in the energy production via glycolysis and other metabolic pathways, and potentially inhibits autophagy, neurogenesis, and immune response by downregulation of signaling pathways. In addition, proteins previously described in several brain pathologies, such as Alzheimer's disease, autism spectrum disorder, amyotrophic lateral sclerosis, and Parkinson's disease, were found with altered expression due to ZIKV infection in hMSC. This potential link between ZIKV and several neuropathologies beyond microcephaly is being described here for the first time and can be used to guide specific follow-up studies concerning these specific diseases and ZIKV infection.