{"doi":"10.1101/2020.02.24.962506","title":"Coevolution of retroviruses with <i>SERINC</i> s following whole-genome duplication divergence","abstract":"Abstract The SERINC gene family comprises of five paralogs in humans of which SERINC3 and SERINC5 inhibit HIV-1 infectivity and are counteracted by Nef. The origin of this anti-retroviral activity, its prevalence among the remaining paralogs, and its ability to target retroviruses remain largely unknown. Here we show that despite their early divergence, the anti-retroviral activity is functionally conserved among four human SERINC paralogs with SERINC 2 being an exception. The lack of activity in human SERINC 2 is associated with its post-whole genome duplication (WGD) divergence, as evidenced by the ability of pre-WGD orthologs from yeast, fly, and a post-WGD-proximate SERINC 2 from coelacanth to inhibit nef-defective HIV-1. Intriguingly, potent retroviral factors from HIV-1 and MLV are not able to relieve the SERINC 2-mediated particle infectivity inhibition, indicating that such activity was directed towards other retroviruses that are found in coelacanth (like foamy viruses). However, foamy-derived vectors are intrinsically resistant to the action of SERINC 2, and we show that a foamy virus envelope confers this resistance. Despite the presence of weak arms-race signatures, the functional reciprocal adaptation among SERINC 2 and SERINC 5 and, in response, the emergence of antagonizing ability in foamy virus appears to have resulted from a long-term conflict with the host.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":128959,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":316633,"name":"Vipin Bhardwaj","orcid":"0000-0003-2076-6794","position":1,"is_corresponding":false},{"id":579699,"name":"Aman Singh","orcid":"0000-0001-8946-4247","position":2,"is_corresponding":false},{"id":579700,"name":"Nagarjun Vijay","orcid":"0000-0002-8703-6991","position":3,"is_corresponding":false},{"id":316635,"name":"Ajit Chande","orcid":"0000-0003-2210-5180","position":4,"is_corresponding":false},{"id":580186,"name":"Pavitra Ramdas","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T23:15:42.522809Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}