  Citation: Piot, N.; Smagghe, G. Critical View on the Importance of Host Defense Strategies on Virus Distribution of Bee Viruses: What Can We Learn from SARS-CoV-2 Variants? Viruses 2022, 14, 503. https://doi.org/10.3390/v14030503 Academic Editor: Michelle Flenniken Received: 19 January 2022 Accepted: 26 February 2022 Published: 28 February 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). viruses Opinion Critical View on the Importance of Host Defense Strategies on Virus Distribution of Bee Viruses: What Can We Learn from SARS-CoV-2 Variants? Niels Piot * and Guy Smagghe * Laboratory of Agrozoology, Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium * Correspondence: niels.piot@ugent.be (N.P.); guy.smagghe@ugent.be (G.S.); Tel.: +32-92-646150 (G.S.) Abstract: Bees, both wild and domesticated ones, are hosts to a plethora of viruses, with most of them infecting a wide range of bee species and genera. Although viral discovery and research on bee viruses date back over 50 years, the last decade is marked by a surge of new studies, new virus discoveries, and reports on viral transmission in and between bee species. This steep increase in research on bee viruses was mainly initiated by the global reports on honeybee colony losses and the worldwide wild bee decline, where viruses are regarded as one of the main drivers. While the knowledge gained on bee viruses has significantly progressed in a short amount of time, we believe that integration of host defense strategies and their effect on viral dynamics in the multi-host viral landscape are important aspects that are currently still missing. With the large epidemiological dataset generated over the last two years on the SARS-CoV-2 pandemic, the role of these defense mechanisms in shaping viral dynamics has become eminent. Integration of these dynamics in a multi-host system would not only greatly aid the understanding of viral dynamics as a driver of wild bee decline, but we believe bee pollinators and their viruses provide an ideal system to study the multi-host viruses and their epidemiology. Keywords: virus tolerance; virus resistance; host; distribution; bee virus variants 1. Viral Defense Strategies of the Host and Their Implications on Viral Dynamics While viral infections may sometimes wreak havoc on host populations, often trig- gered by a host switch, they are indispensable components of a well-functioning ecosys- tem [1,2]. Here, hosts and viruses have co-evolved and live in a dynamic equilibrium, where viruses act as a top-down force controlling host populations. While viruses have evolved a diverse range of host infection routes, the host’s defenses can generally be cate- gorized into two main defense strategies to combat viral infections. Either the hosts can prevent, eliminate, or significantly reduce a viral infection which is generally referred to as viral resistance. A second defense strategy is called viral tolerance. Here, the host can ‘tolerate’ the viral infection and replication without any major detrimental effects on its health [3]. Viral resistance has been investigated for a long time in animal studies, while viral tolerance has only seeped in during the last decade mainly fueled by research from plant pathogens, where tolerance research has a longer history. Both defense strategies benefit the host’s fitness but have different outcomes for viral fitness. Resistant hosts generally reduce the viral prevalence in the population, whereas tolerant hosts mostly have a positive impact on viral prevalence [4,5]. The latter can be induced by so called super-spreaders. These super-spreaders are tolerant hosts, experiencing no or only mild health effects of an infection, and they infect a disproportional number of new hosts, far exceeding the general reproduction number of the virus or pathogen at hand. Here, one could refer to the classic textbook example of Mary Mallon, dubbed “Typhoid Mary”, an asymptomatic carrier of Viruses 2022, 14, 503. https://doi.org/10.3390/v14030503 https://www.mdpi.com/journal/viruses