Tracking Mechanisms of Viral Dissemination In Vivo

Abstract

Dissemination and replication of viruses into hosts is a multistep process where viral particles infect, navigate, and indoctrinate various cell types. Viruses can reach tissues that are distant from their infection site by subverting subcellular mechanisms in ways that are, sometimes, disruptive. Modeling these steps, at appropriate resolution and within animal models, is cumbersome. Yet, mimicking these strategies in vitro fails to recapitulate the complexity of the cellular ecosystem. Here, we will discuss relevant in vivo platforms to dissect the cellular and molecular programs governing viral dissemination and briefly discuss organoid and ex vivo alternatives. We will focus on the zebrafish model and will describe how it provides a transparent window to unravel new cellular mechanisms of viral dissemination in vivo.

Keywords: animal models; intravital imaging; virus; zebrafish.

Figure 1

Strategies to Track Viral Dissemination In Vivo. Viruses employ several strategies to disseminate and reach adjacent tissues (central scheme). They can freely diffuse through the vascular wall when its integrity is altered; they may infect endothelial cells and are released in the extravascular space; and they can be transported across the vascular wall without infection or they can be transported upon infection of circulating immune cells that can stop and cross the endothelium layer. Animal models such as the zebrafish embryo, the mouse model, and the versatile organoids provide very useful imaging and analysis platforms for tracking, at high spatio-temporal resolution, the dynamics and cellular strategies of viral dissemination. For example, intravascular behavior of Zika virus-infected monocytes can be tracked in real time in zebrafish embryos [13]. Budding of HIV-1 from a T cell can be tracked with electron tomography in mice [55]. The inset shows a profile emanating from the surface of a little cytoplasm between the nuclear envelope (NE) and the budding plasma membrane (PM). Dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be tracked in enterocytes of intestinal organoids [45]. Abbreviation: NP, nuclear pore.