Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck

Abstract

The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems.

The Spike of Concern—The Novel Variants of SARS-CoV-2

“…This increases transmission of the virus especially at low viral loads [25]. Any gain in hAce2 binding is of high significance for viral spread, as only a small number of viruses (≤10) are passed on between people or test animals (i.e., SARS-CoV-2 has a small bottleneck of infection) [26,27]. Furthermore, the D614G mutation reduces furin cleavage, thereby lowering the risk of premature S1 shedding, and it enhances thermal stability of spike.…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…Nonetheless, in most SARS-CoV-2 infections, there is one dominant variant throughout the course of the disease and upon onward transmission [279]. Animal experiments on viral evolution and transmission suggest that within-host SARS-CoV-2 variation is predominantly influenced by genetic drift and purifying selection [282]. Due to the low diversity evolving per patient during the comparably short course of infection, the majority of studies focuses on population-wide mutation and evolution analyses (Figures 4 & 6).…”

SARS-CoV-2 Portrayed against HIV: Contrary Viral Strategies in Similar Disguise

“…Nonetheless, in most SARS-CoV-2 infections, there is one dominant variant throughout the course of the disease and upon onward transmission [ 324 ]. Animal experiments on viral evolution and transmission suggest that within-host SARS-CoV-2 variation is predominantly influenced by genetic drift and purifying selection [ 328 ]. Due to the low diversity evolving per patient during the comparably short course of infection, the majority of studies focus on population-wide mutation and evolution analyses ( Figure 4 and Figure 6 ).…”