Nanotechnology seeks to mimic what nature has achieved: self-assembly at the nanometer scale. Viral nanoparticles (VNPs) provide natural examples of self-assembled architectures with unique structural and chemical properties. Here, the utilization of an archaeal virus, Sulfolobus islandicus rod-shaped virus 2 (SIRV2), as a template for site-selective and spatially controlled bioconjugation is described. SIRV2 is a virus of a hyperthermophilic and acidophilic host, the archaeon S. islandicus growing optimally at 80 °C and pH 3, and is thus, by its nature, an extremely stable VNP. The stability of SIRV2 in different solvent/water mixtures is monitored, and it is found that in other, non-natural harsh conditions the VNPs also remained intact. Further, the question of whether the particles offer attachment sites allowing for selective chemical modification and decoration with functional ligands using biotin as a probe is addressed. It is found that carboxylate-, carbohydrate- and amine-selective chemistries are applicable and various biotinylated SIRV2 formulations can be fabricated. Depending on the chemistry and hence attachment site used, the display of the biotin labels can be spatially controlled at the virus body and at the ends. Labeling studies also provide novel insights into the structural properties of SIRV2, indicating that the major coat protein (CP) forms the virus body while the minor CP is located in the tail fibers at the end of the particles. Overall, SIRV2 represents an extremely stable and structurally interesting VNP with the potential for novel nanobiotechnological applications.