{"doi":"10.1128/jvi.01950-24","title":"Genome evolution of Kaposi sarcoma-associated herpesvirus (KSHV)","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:sec>\n            <jats:title/>\n            <jats:p>\n              Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH), particularly in sub-Saharan Africa (SSA), where Kaposi sarcoma herpesvirus (KSHV or human herpesvirus 8 [HHV-8]) is endemic. In KSHV endemic areas, the overall survival of KS patients has changed little over the past 20 years. A phylogenetic analysis of available full-length viral genomes (\n              <jats:italic toggle=\"yes\">n</jats:italic>\n              = 164) identified two different virus lineages that co-circulate in KSHV endemic regions today. Their sequences differ from the GenBank reference sequence and those of common laboratory strains, which originated in the 1990s in the US and Europe. Targeted short-read sequencing accuracy was validated by PacBio-based long-read sequencing to resolve repeats. This analysis identified over 1,000 single nucleotide variants (SNV) in a new 14-member sequence collection from tumor biopsies and blood in Malawi with 127 ± 32 (median ± SD) SNV per genome. Most were private, i.e., specific to one individual’s virus. Within each of the two lineages, KSHV continues to evolve over time and across national borders by genetic drift and recombination. Analyses of shared SNVs by AlphaFold2 predicted some changes in the conformation of key viral proteins. These findings may help our understanding of herpesvirus evolution.\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE</jats:title>\n            <jats:p>To understand viruses, the field needs to know their genetic makeup. To develop mechanistic models, targeted therapies, and vaccines, we need comprehensive and up-to-date sequence information on the viral strains that circulate where the diseases appear today. Our knowledge of Kaposi sarcoma herpesvirus (KSHV) sequence distribution and evolution is behind that of other human herpesviruses and RNA viruses. Here, we add to community knowledge using new technologies and artificial intelligence.</jats:p>\n          </jats:sec>","journal":"Journal of Virology","year":2025,"id":612588,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1048823,"name":"Alice Peng","orcid":"0000-0003-1877-2001","position":1,"is_corresponding":false},{"id":1577386,"name":"Justin Landis","orcid":null,"position":2,"is_corresponding":false},{"id":1577387,"name":"Linda J. Pluta","orcid":null,"position":3,"is_corresponding":false},{"id":880891,"name":"Patricio Cano","orcid":"0000-0003-2948-3475","position":4,"is_corresponding":false},{"id":334458,"name":"Angelica Juarez","orcid":"0000-0003-2342-0078","position":5,"is_corresponding":false},{"id":295812,"name":"Dirk P. Dittmer","orcid":"0000-0003-4968-5656","position":6,"is_corresponding":false},{"id":334450,"name":"Razia Moorad","orcid":"0000-0001-5688-5766","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Genome evolution of Kaposi sarcoma-associated herpesvirus (KSHV)","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:sec>\n            <jats:title/>\n            <jats:p>\n              Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH), particularly in sub-Saharan Africa (SSA), where Kaposi sarcoma herpesvirus (KSHV or human herpesvirus 8 [HHV-8]) is endemic. In KSHV endemic areas, the overall survival of KS patients has changed little over the past 20 years. A phylogenetic analysis of available full-length viral genomes (\n              <jats:italic toggle=\"yes\">n</jats:italic>\n              = 164) identified two different virus lineages that co-circulate in KSHV endemic regions today. Their sequences differ from the GenBank reference sequence and those of common laboratory strains, which originated in the 1990s in the US and Europe. Targeted short-read sequencing accuracy was validated by PacBio-based long-read sequencing to resolve repeats. This analysis identified over 1,000 single nucleotide variants (SNV) in a new 14-member sequence collection from tumor biopsies and blood in Malawi with 127 ± 32 (median ± SD) SNV per genome. Most were private, i.e., specific to one individual’s virus. Within each of the two lineages, KSHV continues to evolve over time and across national borders by genetic drift and recombination. Analyses of shared SNVs by AlphaFold2 predicted some changes in the conformation of key viral proteins. These findings may help our understanding of herpesvirus evolution.\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE</jats:title>\n            <jats:p>To understand viruses, the field needs to know their genetic makeup. To develop mechanistic models, targeted therapies, and vaccines, we need comprehensive and up-to-date sequence information on the viral strains that circulate where the diseases appear today. Our knowledge of Kaposi sarcoma herpesvirus (KSHV) sequence distribution and evolution is behind that of other human herpesviruses and RNA viruses. Here, we add to community knowledge using new technologies and artificial intelligence.</jats:p>\n          </jats:sec>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40237497","pmcid":"PMC12090769","openalex_id":"https://openalex.org/W4409484602","authors":[],"funders":[{"funder_name":"National Institute of Dental and Craniofacial Research","grant_id":"DE018304","title":null},{"funder_name":"National Cancer Institute","grant_id":"CA16086","title":null},{"funder_name":"National Cancer Institute","grant_id":"CA121947","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P01 CA019014","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA016086","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA239583","title":null},{"funder_name":"NCI NIH HHS","grant_id":"UM1 CA121947","title":null},{"funder_name":"NIDCR NIH HHS","grant_id":"R01 DE018304","title":null},{"funder_name":"NCI NIH HHS","grant_id":"U01 CA121947","title":null},{"funder_name":"NCI NIH HHS","grant_id":"U54 CA254564","title":null}],"total_grants":10,"fwci":1.4731,"citation_percentile":0.8228808,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1128/jvi.01950-24","host_type":"journal"},{"url":"https://doi.org/10.1128/jvi.01950-24","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/jvi.01950-24","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40237497","host_type":"repository"},{"url":"https://doi.org/10.17615/apmt-hk82","host_type":"repository"},{"url":"https://doaj.org/article/ea6a89dd8e4e4c5885fe195514529d6c","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12090769","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12090769","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12090769?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Viral-associated cancers and disorders","Biological Research and Disease Studies","Herpesvirus Infections and Treatments","Herpesvirus 8, Human","Humans","Genome, Viral","Phylogeny","Sarcoma, Kaposi","Evolution, Molecular","Malawi","Viral Proteins"],"mesh_terms":["Humans","Malawi","Phylogeny","Sarcoma, Kaposi","Viral Proteins","Genome, Viral","Evolution, Molecular","Herpesvirus 8, Human"],"keywords":["Biology","GenBank","Kaposi's sarcoma-associated herpesvirus","Virology","Genome","Phylogenetic tree","Viral evolution","Genetics","Virus","Sarcoma","Sequence (biology)","Whole genome sequencing","Virus classification","DNA sequencing","Gene","Viral disease","Herpesviridae","Evolution","Human herpesvirus 8","Kaposi's sarcoma","Kshv","Kaposi Sarcoma-associated Herpesvirus","Pacbio","Kaposi Sarcoma Herpesvirus","Human Herpesviruses","Alphafold"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"bioproject"},{"name":"gen"},{"name":"refseq"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T04:09:25.130678Z","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":[]}