Abstract

Viruses from the third domain of life, Archaea, exhibit unusual features including extreme stability that allow their survival in harsh environments. In addition, these species have never been reported to integrate into human or any other eukaryotic genomes, and could thus serve for exploration of novel medical nanoplatforms. Here, we selected two archaeal viruses Sulfolobus monocaudavirus 1 (SMV1) and Sulfolobus spindle shaped virus 2 (SSV2) owing to their unique spindle shape, hyperthermostable and acid-resistant nature and studied their interaction with mammalian cells. Accordingly, we followed viral uptake, intracellular trafficking and cell viability in human endothelial cells of brain (hCMEC/D3 cells) and umbilical vein (HUVEC) origin. Whereas SMV1 is efficiently internalized into both types of human cells, SSV2 differentiates between HUVECs and hCMEC/D3 cells, thus opening a path for selective cell targeting. On internalization, both viruses localize to the lysosomal compartments. Neither SMV1, nor SSV2 induced any detrimental effect on cell morphology, plasma membrane and mitochondrial functionality. This is the first study demonstrating recognition of archaeal viruses by eukaryotic cells which provides good basis for future exploration of archaeal viruses in bioengineering and development of multifunctional vectors.

Highlights

  • Archaeal viruses offer an ideal search pool for novel nanoplatforms as they have several attractive features

  • We have investigated the uptake, intracellular fate, and safety of fluorescently labelled Sulfolobus monocaudavirus 1 (SMV1) and spindle shaped virus 2 (SSV2) in two different endothelial cell types of human origin: hCMEC/D3 and Human umbilical vein endothelial cells (HUVECs), providing the first insights into the interaction between archaeal viruses and eukaryotic cells

  • SMV1 appears both individually and in a rosette-like arrangement, where virus-virus interaction appears to be mediated through the tail regions

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Summary

Introduction

Archaeal viruses offer an ideal search pool for novel nanoplatforms as they have several attractive features They are non-pathogenic, offer unique morphologies, and have specializations to survive in extreme environments[6]. Archaeal viruses show distinct morphologies not found in bacteriophages or plant viruses These include spindle-, bottle-, and droplet-shape[6]. We studied two archaeal viruses; Sulfolobus monocaudavirus 1 (SMV1) and Sulfolobus spindle shaped virus 2 (SSV2) as candidate nanoplatforms. Both viruses infect hosts from the archaeal genus Sulfolobus which are found in volcanic hot springs, and are considered hyperthermophilic acidophiles with optimal growth at 80 °C and pH 2–313. SMV1 and SSV2 were selected owing to their unique spindle-shape, hyperthermostable and acid-resistant nature Both species are well-established laboratory strains with the potential for up scaling. We have investigated the uptake, intracellular fate, and safety of fluorescently labelled SMV1 and SSV2 in two different endothelial cell types of human origin: hCMEC/D3 and HUVEC, providing the first insights into the interaction between archaeal viruses and eukaryotic cells

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