Classification of small ruminant lentivirus subtype A2, subgroups 1 and 2 based on whole genome comparisons and complex recombination patterns

Authors

Aaron M. Dickey, USDA-ARS, MARCFollow
Timothy P.L. Smith, USDA-ARS, MARCFollow
Michael L. Clawson, USDA-ARS, MARCFollow
Michael P. Heaton, USDA-ARS, MARCFollow
Aspen M. Workman, USDA-ARS, MARCFollow

ORCID IDs

Aaron M. Dickey https://orcid.org/0000-0003-1250-1390

Timothy P. L. Smith https://orcid.org/0000-0003-1611-6828

Michael P. Heaton https://orcid.org/0000-0003-1386-1208

Date of this Version

12-11-2020

Document Type

Article

Citation

Dickey AM, Smith TPL, Clawson ML et al. Classification of small ruminant lentivirus subtype A2, subgroups 1 and 2 based on whole genome comparisons and complex recombination patterns [version 1; peer review: awaiting peer review] F1000Research 2020, 9:1449 https://doi.org/10.12688/f1000research.27898.1

Comments

Copyright: © 2020 Dickey AM et al. This is an open access article distributed under the terms of the Creative Commons Attribution License

Abstract

Background: Small ruminant lentiviruses (SRLVs) cause a multisystemic chronic wasting disease in sheep across much of the world. SRLV subtype A2 is prevalent in North America and further classified into multiple subgroups based on variation in the group antigens gene (gag) and envelope (env) genes. In sheep, the ovine transmembrane protein 154 (TMEM154) gene is associated with SRLV susceptibility. Ewes with at least one copy of TMEM154 encoding a fulllength protein with glutamate at position 35 (E35; haplotypes 2 and 3), are highly susceptible to SRLV infection while ewes with any combination of TMEM154 haplotypes which encodes lysine (K35; haplotype 1), or truncated proteins (haplotypes 4 and 6) are several times less so. A2 subgroups 1 and 2 are associated with host TMEM154 genotypes; subgroup 1 with the K35/K35 genotype and subgroup 2 with the E35/E35 genotype.

Methods: The goals of this study were to analyze sequence variation within and among SRLV subtype A2 subgroups 1 and 2 and to identify genome-scale recombination patterns. This was done using full-length assemblies of virus samples.

Results: Consensus viral genomes were assembled for 23 infected sheep, including animals of assorted TMEM154 genotypes comprised of haplotypes 1, 2, or 3. Viral genome analysis identified viral subgroups 1 and 2 among the samples, and revealed additional substructure within subgroup 2 based on models predicting complex patterns of recombination between the two subgroups in several genomes. Animals with evidence of dual subgroup infection also possessed the most diverse quasi-species and the most highly recombined genomes.

Conclusions: The viral subgroup framework developed to classify SRLV consensus genomes along a continuum of recombination suggests that animals with the TMEM154 E35/K35 genotype may represent a reservoir for producing viral genomes representing recombination between A2 subgroups 1 and 2.