From one to many: The within-host rise of viral variants

Over the course of a viral infection, a tremendous number of virions are produced: up to 10—more than there are stars in the Milky Way [1]. These viruses do not exist as a genetically identical population. Genetic changes are constantly occurring, especially for RNA viruses, creating a cloud of genetically related variants [2]. Viral evolution within the infected host is shaped by host and viral factors. Repeatedly, in the history of viral diseases, new strains have emerged with selective advantages, such as drug resistance or enhanced transmissibility. For example, a few months after the Severe Acute Respiratory Syndrome Coronavirus 2 (SAU : Pleasenotethat}SARS CoV 2}hasbeendefinedas}SevereAcuteRespiratorySyndromeCoronavirus2}inthesentence}Forexample; afewmonthsafterthe:::}:Pleasecheckandcorrectifnecessary: RS-CoV-2) emergence, variants with enhanced infectivity have spread worldwide [3]. At the origin of each of these emergences, at least one infected host has been the scene of a competition between the newly arisen variant and its progenitors. Viral populations face bottlenecks (events reducing the population size, and, therefore, its genetic diversity) that can be divided into 2 categories: transmission bottlenecks and withinhost bottlenecks, which we will discuss here [4]. We propose that, in order to emerge, a variant has to overcome the within-host bottlenecks by winning the competition against its progenitors, allowing it to be transmitted and selected.