The role of reverse genetics systems in studying viral hemorrhagic fevers

A number of viral infectious diseases have emerged or reemerged from wildlife vectors that have generated serious threats to global health. Increased international traveling and commerce increase the risk of transmission of viral or other infectious diseases. In addition, recent climate changes accelerate the potential spread of domestic disease. The Coronavirus disease 2019 (COVID-19) pandemic is an important example of the worldwide spread, and the current epidemic will unlikely be the last. Viral hemorrhagic fevers, such as Dengue and Lassa fevers, may also have the potential to spread worldwide with a significant impact on public health with unpredictable timing. Based on the important lessons learned from COVID-19, it would be prudent to prepare for future pandemics of life-threatening viral diseases. Among the various threats, this review focuses on the coagulopathy of acute viral infections since hypercoagulability has been a major challenge in COVID-19, but represents a different presentation compared to viral hemorrhagic fever. However, both thrombosis and hemorrhage are understood as the result of thromboinflammation due to viral infections, and the role of anticoagulation is important to consider.

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Centrin2 regulates CP110 removal in primary cilium formation

The Journal of Cell Biology ◽

10.1083/jcb.201411070 ◽

2015 ◽

Vol 208 (6) ◽

pp. 693-701 ◽

Cited By ~ 38

Author(s):

Suzanna L. Prosser ◽

Ciaran G. Morrison

Keyword(s):

Calcium Binding ◽

Primary Cilia ◽

Reverse Genetics ◽

Cell Types ◽

Serum Starvation ◽

Basal Bodies ◽

Cilium Formation ◽

Cellular Quiescence ◽

Retinal Pigmented Epithelial Cells

Primary cilia are antenna-like sensory microtubule structures that extend from basal bodies, plasma membrane–docked mother centrioles. Cellular quiescence potentiates ciliogenesis, but the regulation of basal body formation is not fully understood. We used reverse genetics to test the role of the small calcium-binding protein, centrin2, in ciliogenesis. Primary cilia arise in most cell types but have not been described in lymphocytes. We show here that serum starvation of transformed, cultured B and T cells caused primary ciliogenesis. Efficient ciliogenesis in chicken DT40 B lymphocytes required centrin2. We disrupted CETN2 in human retinal pigmented epithelial cells, and despite having intact centrioles, they were unable to make cilia upon serum starvation, showing abnormal localization of distal appendage proteins and failing to remove the ciliation inhibitor CP110. Knockdown of CP110 rescued ciliation in CETN2-deficient cells. Thus, centrin2 regulates primary ciliogenesis through controlling CP110 levels.

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