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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, escape human immunity 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, but dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. Transmission bottlenecks in this system appear narrow, with new infections being founded by fewer than ten viruses. We identify a notable variant at amino acid position 655 in Spike (H655Y) which arises rapidly in index cats and becomes fixed following transmission in two of three pairs, suggesting this site may be under positive selection in feline hosts. We speculate that narrow transmission bottlenecks and the lack of pervasive positive selection combine to constrain the pace of ongoing SARS-CoV-2 adaptive evolution in mammalian hosts.

SUBMITTER: Braun KM

PROVIDER: S-EPMC7685321 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Braun Katarina M KM Moreno Gage K GK Halfmann Peter J PJ Hodcroft Emma B EB Baker David A DA Boehm Emma C EC Weiler Andrea M AM Haj Amelia K AK Hatta Masato M Chiba Shiho S Maemura Tadashi T Kawaoka Yoshihiro Y Koelle Katia K O'Connor David H DH Friedrich Thomas C TC

bioRxiv : the preprint server for biology 20210104

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 amin ...[more]

PMID: 33236011

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Project description:SARS-CoV-2 (SARS2) infection of a novel permissive host species can result in rapid viral evolution. Data suggest that felids are highly susceptible to SARS2 infection, and species-specific adaptation following human-to-felid transmission may occur. We employed experimental infection and analysis of publicly available SARS2 sequences to observe variant emergence and selection in domestic cats. Three cohorts of cats (N = 23) were inoculated with SARS-CoV-2 USA-WA1/2020 or infected via cat-to-cat contact transmission. Full viral genomes were recovered from RNA obtained from nasal washes 1-3 days post-infection and analyzed for within-host viral variants. We detected 118 unique variants at ≥3 per cent allele frequency in two technical replicates. Seventy of these (59 per cent) were nonsynonymous single nucleotide variants (SNVs); the remainder were synonymous SNVs or structural variants. On average, we observed twelve variants per cat, nearly 10-fold higher than what is commonly reported in human patients. We observed signatures of positive selection in the spike protein and the emergence of eleven within-host variants located at the same genomic positions as mutations in SARS2 variant lineages that have emerged during the pandemic. Fewer variants were noted in cats infected from contact with other cats and in cats exposed to lower doses of cultured inoculum. An analysis of ninety-three publicly available SARS2 consensus genomes recovered from naturally infected domestic cats reflected variant lineages circulating in the local human population at the time of sampling, illustrating that cats are susceptible to SARS2 variants that have emerged in humans, and suggesting human-to-felid transmission occurring in domestic settings is typically unidirectional. These experimental results underscore the rapidity of SARS2 adaptation in felid hosts, representing a theoretical potential origin for variant lineages in human populations. Further, cats should be considered susceptible hosts capable of shedding virus during infections occurring within households.

Dataset Information

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

Publications

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

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