Virus Evolution最新文献

{"title":"Combined use of pritelivir with acyclovir or foscarnet suppresses evolution of HSV-1 drug resistance.","authors":"Hanna Helena Schalkwijk, Graciela Andrei, Robert Snoeck","doi":"10.1093/ve/veae101","DOIUrl":"10.1093/ve/veae101","url":null,"abstract":"<p><p>The widespread use of antivirals in immunocompromised individuals has led to frequent occurrences of drug-resistant herpes simplex virus 1 (HSV-1) infections. Current antivirals target the viral DNA polymerase (DP), resulting in cross-resistance patterns that emphasize the need for novel treatment strategies. In this study, we assessed whether combining antivirals with different targets affects drug resistance emergence by passaging wild-type HSV-1 under increasing concentrations of acyclovir (ACV), foscarnet (phosphonoformic acid, PFA), or the helicase-primase inhibitor pritelivir (PTV), individually or in combination (ACV + PTV or PFA + PTV). The resistance selection procedure was initiated from two different drug concentrations for each condition. Deep sequencing and subsequent phenotyping showed the rapid acquisition of resistance mutations under monotherapy pressure, whereas combination therapy resulted in either no mutations or mutations conferring ACV and/or PFA resistance. Notably, mutations associated with PTV resistance were not detected after five passages under combination pressure. Strains resistant to both ACV and PTV were eventually obtained upon further passaging under ACV + PTV pressure initiated from lower drug concentrations. PFA + PTV dual treatment induced PFA resistance mutations in the DP, but PTV resistance mutations were not acquired, even after 15 passages. Our data suggest that combining the helicase-primase inhibitor PTV with a DP inhibitor may be an effective strategy to prevent drug resistance evolution in HSV-1.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae101"},"PeriodicalIF":5.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of Omicron FN.1 a descendent of BQ.1.1 in Botswana.","authors":"Wonderful T Choga, Emanuele Gustani-Buss, Houriiyah Tegally, Dorcas Maruapula, Xiaoyu Yu, Monika Moir, Boitumelo J L Zuze, San Emmanuel James, Nokuthula S Ndlovu, Kedumetse Seru, Patience Motshosi, Alexandra Blenkinsop, Irene Gobe, Cheryl Baxter, Justen Manasa, Shahin Lockman, Roger Shapiro, Joseph Makhema, Eduan Wilkinson, Jason T Blackard, Phillipe Lemey, Richard J Lessells, Darren P Martin, Tulio de Oliveira, Simani Gaseitsiwe, Sikhulile Moyo","doi":"10.1093/ve/veae095","DOIUrl":"10.1093/ve/veae095","url":null,"abstract":"<p><p>Botswana, like the rest of the world, has been significantly impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In December 2022, we detected a monophyletic cluster of genomes comprising a sublineage of the Omicron variant of concern (VOC) designated as B.1.1.529.5.3.1.1.1.1.1.1.74.1 (alias FN.1, clade 22E). These genomes were sourced from both epidemiologically linked and unlinked samples collected in three close locations within the district of Greater Gaborone. In this study, we assessed the worldwide prevalence of the FN.1 lineage, evaluated its mutational profile, and conducted a phylogeographic analysis to reveal its global dispersal dynamics. Among approximately 16 million publicly available SARS-CoV-2 sequences generated by 30 September 2023, only 87 were of the FN.1 lineage, including 22 from Botswana, 6 from South Africa, and 59 from the UK. The estimated time to the most recent common ancestor of the 87 FN.1 sequences was 22 October 2022 [95% highest posterior density: 2 September 2022-24 November 2022], with the earliest of the 22 Botswana sequences having been sampled on 7 December 2022. Discrete trait reconstruction of FN.1 identified Botswana as the most probable place of origin. The FN.1 lineage is derived from the BQ.1.1 lineage and carries two missense variants in the spike protein, S:K182E in NTD and S:T478R in RDB. Among the over 90 SARS-CoV-2 lineages circulating in Botswana between September 2020 and July 2023, FN.1 was most closely related to BQ.1.1.74 based on maximum likelihood phylogenetic inference, differing only by the S:K182E mutation found in FN.1. Given the early detection of numerous novel variants from Botswana and its neighbouring countries, our study underscores the necessity of continuous surveillance to monitor the emergence of potential VOCs, integrating molecular and spatial data to identify dissemination patterns enhancing preparedness efforts.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae095"},"PeriodicalIF":5.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A critique of the use of species and below-species taxonomic terms for viruses-time for change?","authors":"Peter Simmonds","doi":"10.1093/ve/veae096","DOIUrl":"10.1093/ve/veae096","url":null,"abstract":"<p><p>The International Committee for the Taxonomy of Viruses (ICTV) regulates assignment and names of virus species and higher taxa through its taxonomy proposal and ratification process. Despite using similar taxonomic ranks to those used elsewhere in biology, the ICTV has maintained the principle that species and other taxa are strictly categories with a formal nomenclature, whereas the viruses as objects are referenced through a parallel inventory of community-assigned virus names. This is strikingly different from common and scientific name synonyms for species used elsewhere in biology. The recent introduction of binomial names for virus species resembling biological scientific names has intensified this confusion in terms within the virology community and beyond. The ICTV taxonomy furthermore does not engage with or regulate classification below species and consequently lacks taxonomic terms or descriptions for important viral pathogens such as polioviruses, severe acute respiratory syndrome coronavirus type 2, HIV-1, and avian influenza as examples. The consequent reliance on community-adopted virus names, genotypes, and other categories often lacks clarity for clinical, biocontainment, and other regulatory purposes. This article proposes a revision of rules and procedures for species and below-species level classification. It recasts virus and virus species names as 'common' and 'scientific' names that are used in other biology nomenclature codes, each with expanded reference to both object and taxon. It further advocates the creation of a formal below-species taxonomic rank to define a new inventory of approved taxa and specified nomenclature below species. Adoption of the proposed changes will realign virus taxonomy with other biological nomenclatural codes and provide greater transparency and clarity in virology, medical, and regulatory fields.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae096"},"PeriodicalIF":5.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mathematical comparison of protocols for adapting a bacteriophage to a new host.","authors":"James J Bull, Stephen M Krone","doi":"10.1093/ve/veae100","DOIUrl":"10.1093/ve/veae100","url":null,"abstract":"<p><p>Interest in phage therapy-the use of bacterial viruses to treat infections-has increased recently because of the rise of infections with antibiotic-resistant bacteria and the failure to develop new antibiotics to treat those infections. Phages have shown therapeutic promise in recent work, and successful treatment minimally requires giving the patient a phage that will grow on their infecting bacterium. Although nature offers a bountiful and diverse supply of phages, there have been a surprising number of patient infections that could not be treated with phages because no suitable phage was found to kill the patient's bacterium. Here, we develop computational models to analyze an alternative approach to obtaining phages with new host ranges-directed evolution via laboratory propagation of phages to select mutants that can grow on a new host. The models separately explore alternative directed evolution protocols for phage variants that overcome three types of bacterial blocks to phage growth: a block in adsorption, temperate phage immunity to superinfection, and abortive infection. Protocols assume serial transfer to amplify pre-existing, small-effect mutants that are initially rare. Best protocols are sensitive to the nature of the block, and the models provide several insights for enhancing success specific to each case. A common result is that low dilution rates between transfers are beneficial in reducing the mutant growth rate needed to ascend. Selection to overcome an adsorption block is insensitive to many protocol variations but benefits from long selection times between transfers. A temperate phage selected to grow on its lysogens can evolve in any of three phenotypes, but a common protocol favors the desired changes in all three. Abortive infection appears to be the least amenable to evolving phage growth because it is prone to select phages that avoid infection.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae100"},"PeriodicalIF":5.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the genomic landscape of piscine myocarditis virus: mutation frequencies, viral diversity and evolutionary dynamics in Atlantic salmon.","authors":"Racheal Amono, Turhan Markussen, Vikash K Singh, Morten Lund, Farah Manji, Sunil K Mor, Øystein Evensen, Aase B Mikalsen","doi":"10.1093/ve/veae097","DOIUrl":"10.1093/ve/veae097","url":null,"abstract":"<p><p>Over a decade since its discovery, piscine myocarditis virus (PMCV) remains a significant pathogen in Atlantic salmon aquaculture. Despite this significant impact, the genomic landscape, evolutionary dynamics, and virulence factors of PMCV are poorly understood. This study enhances the existing PMCV sequence dataset by adding 34 genome sequences and 202 new ORF3 sequences from clinical cardiomyopathy syndrome (CMS) cases in Norwegian aquaculture. Phylogenetic analyses, also including sequences from the Faroe Islands and Ireland revealed that PMCV sequences are highly conserved with distinct clustering by country of origin. Still, single CMS outbreaks display multiple PMCV variants, and although some clustering was seen by case origin, occasional grouping of sequences from different cases was also apparent. Temporal data from selected cases indicated increased sequence diversity in the population. We hypothesize that multiple bottlenecks and changing infection dynamics in the host population, with transfer to naïve individuals over time, represent a continuous selection pressure on the virus populations. No clear relation was found between PMCV variants and the severity of heart pathology. However, specific non-synonymous and synonymous mutations that might impact protein function and gene expression efficiency were identified. An additional factor that may impact PMCV replication is the presence of defective viral genomes, a novel finding for viruses of the order <i>Ghabrivirales</i>. This study provides new insights into PMCV genomic characteristics and evolutionary dynamics, highlighting the complex interplay of genetic diversity, virulence markers, and host-pathogen interactions, underscoring the epidemiological complexity of the virus. Keywords: piscine myocarditis virus; evolutionary dynamics; diversity; phylogeny; genomic sequencing; defective viral genomes.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae097"},"PeriodicalIF":5.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of a novel engineered tripartite viral genome of a torradovirus.","authors":"Massimo Turina, Luca Nerva, Marta Vallino, Niccolò Miotti, Marco Forgia, Marina Ciuffo, Bryce W Falk, Inmaculada Ferriol","doi":"10.1093/ve/veae098","DOIUrl":"10.1093/ve/veae098","url":null,"abstract":"<p><p>Viruses in the <i>Secoviridae</i> include monopartite and bipartite genomes, suggesting the possibility to study members of this family to experimentally address evolutionary transitions resulting in multipartitism. Torradoviruses are bipartite members of the family <i>Secoviridae</i> characterized by a genus-specific 5' open reading frame, named P21, encoded by RNA2. Here, in a study originally intended to verify if P21 can function <i>in trans</i>, we attempted to provide P21 from a third P21-expressing construct under control of the 35S promoter and containing the 5'- and 3'-untranslated regions (UTRs) of wild-type (WT) RNA2. When this construct was combined with an RNA2 with a complete deletion of the P21 coding region we verified that the P21 provided <i>in trans</i> cannot immediately complement the mutant, but occasional systemic infections in a limited number of the inoculated plants display the presence of a tripartite virus with an actively replicating P21-expressing RNA3. Furthermore, in all the systemically infected plants investigated in six distinct experiments, this replicating RNA3 accumulates deletions in a small region inside the original 3'-UTR provided by the cDNA clone. Such tripartite virus, which we obtained through deconstructing the coding potential of the RNA2 in two distinct RNAs, can be transmitted mechanically and by whiteflies, is competent for virion formation, and its RNA3 is encapsidated. It can be mechanically transferred for 11 serial passages without losing its infectivity or showing major genomic rearrangements. Furthermore, mixing equal amounts of WT and tripartite virus inocula in the same leaf resulted in plants systemically infected only with the WT virus, showing that the tripartite virus has lower fitness than the WT. To our knowledge, this is the first example of an engineered tripartite viral genome becoming stable through artificial evolution <i>in vivo</i>, in plants. This tripartite system was also used to derive a stable viral vector to express green fluorescence protein (GFP) systemically in the context of viral infection.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"0"},"PeriodicalIF":5.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CovTransformer: A transformer model for SARS-CoV-2 lineage frequency forecasting.","authors":"Yinan Feng, Emma E Goldberg, Michael Kupperman, Xitong Zhang, Youzuo Lin, Ruian Ke","doi":"10.1093/ve/veae086","DOIUrl":"10.1093/ve/veae086","url":null,"abstract":"<p><p>With hundreds of SARS-CoV-2 lineages circulating in the global population, there is an ongoing need for predicting and forecasting lineage frequencies and thus identifying rapidly expanding lineages. Accurate prediction would allow for more focused experimental efforts to understand pathogenicity of future dominating lineages and characterize the extent of their immune escape. Here, we first show that the inherent noise and biases in lineage frequency data make a commonly-used regression-based approach unreliable. To address this weakness, we constructed a machine learning model for SARS-CoV-2 lineage frequency forecasting, called CovTransformer, based on the transformer architecture. We designed our model to navigate challenges such as a limited amount of data with high levels of noise and bias. We first trained and tested the model using data from the UK and the USA, and then tested the generalization ability of the model to many other countries and US states. Remarkably, the trained model makes accurate predictions two months into the future with high levels of accuracy both globally (in 31 countries with high levels of sequencing effort) and at the US-state level. Our model performed substantially better than a widely used forecasting tool, the multinomial regression model implemented in Nextstrain, demonstrating its utility in SARS-CoV-2 monitoring. Assuming a newly emerged lineage is identified and assigned, our test using retrospective data shows that our model is able to identify the dominating lineages 7 weeks in advance on average before they became dominant. Overall, our work demonstrates that transformer models represent a promising approach for SARS-CoV-2 forecasting and pandemic monitoring.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae086"},"PeriodicalIF":5.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimensionality reduction distills complex evolutionary relationships in seasonal influenza and SARS-CoV-2.","authors":"Sravani Nanduri, Allison Black, Trevor Bedford, John Huddleston","doi":"10.1093/ve/veae087","DOIUrl":"10.1093/ve/veae087","url":null,"abstract":"<p><p>Public health researchers and practitioners commonly infer phylogenies from viral genome sequences to understand transmission dynamics and identify clusters of genetically-related samples. However, viruses that reassort or recombine violate phylogenetic assumptions and require more sophisticated methods. Even when phylogenies are appropriate, they can be unnecessary or difficult to interpret without specialty knowledge. For example, pairwise distances between sequences can be enough to identify clusters of related samples or assign new samples to existing phylogenetic clusters. In this work, we tested whether dimensionality reduction methods could capture known genetic groups within two human pathogenic viruses that cause substantial human morbidity and mortality and frequently reassort or recombine, respectively: seasonal influenza A/H3N2 and SARS-CoV-2. We applied principal component analysis, multidimensional scaling (MDS), t-distributed stochastic neighbor embedding (t-SNE), and uniform manifold approximation and projection to sequences with well-defined phylogenetic clades and either reassortment (H3N2) or recombination (SARS-CoV-2). For each low-dimensional embedding of sequences, we calculated the correlation between pairwise genetic and Euclidean distances in the embedding and applied a hierarchical clustering method to identify clusters in the embedding. We measured the accuracy of clusters compared to previously defined phylogenetic clades, reassortment clusters, or recombinant lineages. We found that MDS embeddings accurately represented pairwise genetic distances including the intermediate placement of recombinant SARS-CoV-2 lineages between parental lineages. Clusters from t-SNE embeddings accurately recapitulated known phylogenetic clades, H3N2 reassortment groups, and SARS-CoV-2 recombinant lineages. We show that simple statistical methods without a biological model can accurately represent known genetic relationships for relevant human pathogenic viruses. Our open source implementation of these methods for analysis of viral genome sequences can be easily applied when phylogenetic methods are either unnecessary or inappropriate.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae087"},"PeriodicalIF":5.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple phylogenetic approach to analyze hypermutated HIV proviruses reveals insights into their dynamics and persistence during antiretroviral therapy.","authors":"Aniqa Shahid, Bradley R Jones, Maggie C Duncan, Signe MacLennan, Michael J Dapp, Mark H Kuniholm, Bradley Aouizerat, Nancie M Archin, Stephen Gange, Igho Ofotokun, Margaret A Fischl, Seble Kassaye, Harris Goldstein, Kathryn Anastos, Jeffrey B Joy, Zabrina L Brumme","doi":"10.1093/ve/veae094","DOIUrl":"10.1093/ve/veae094","url":null,"abstract":"<p><p>Hypermutated proviruses, which arise in a single Human Immunodeficiency Virus (HIV) replication cycle when host antiviral APOBEC3 proteins introduce extensive guanine to adenine mutations throughout the viral genome, persist in all people living with HIV receiving antiretroviral therapy (ART). However, hypermutated sequences are routinely excluded from phylogenetic trees because their extensive mutations complicate phylogenetic inference, and as a result, we know relatively little about their within-host evolutionary origins and dynamics. Using >1400 longitudinal single-genome-amplified HIV <i>env-gp120</i> sequences isolated from six women over a median of 18 years of follow-up-including plasma HIV RNA sequences collected over a median of 9 years between seroconversion and ART initiation, and >500 proviruses isolated over a median of 9 years on ART-we evaluated three approaches for masking hypermutation in nucleotide alignments. Our goals were to (i) reconstruct phylogenies that can be used for molecular dating and (ii) phylogenetically infer the integration dates of hypermutated proviruses persisting during ART. Two of the approaches (stripping all positions containing putative APOBEC3 mutations from the alignment or replacing individual putative APOBEC3 mutations in hypermutated sequences with the ambiguous base R) consistently normalized tree topologies, eliminated erroneous clustering of hypermutated proviruses, and brought <i>env</i>-intact and hypermutated proviruses into comparable ranges with respect to multiple tree-based metrics. Importantly, these corrected trees produced integration date estimates for <i>env</i>-intact proviruses that were highly concordant with those from benchmark trees that excluded hypermutated sequences, supporting the use of these corrected trees for molecular dating. Subsequent molecular dating of hypermutated proviruses revealed that these sequences spanned a wide within-host age range, with the oldest ones dating to shortly after infection. This indicates that hypermutated proviruses, like other provirus types, begin to be seeded into the proviral pool immediately following infection and can persist for decades. In two of the six participants, hypermutated proviruses differed from <i>env</i>-intact ones in terms of their age distributions, suggesting that different provirus types decay at heterogeneous rates in some hosts. These simple approaches to reconstruct hypermutated provirus' evolutionary histories reveal insights into their <i>in vivo</i> origins and longevity toward a more comprehensive understanding of HIV persistence during ART.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veae094"},"PeriodicalIF":5.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phylogenetic assessment of HIV-1 transmission trends among people who inject drugs from Coastal and Nairobi, Kenya.","authors":"Hanley Kingston, George Nduva, Bhavna H Chohan, Loice Mbogo, Aliza Monroe-Wise, Betsy Sambai, Brandon L Guthrie, Eduan Wilkinson, Jennifer Giandhari, Sarah Masyuko, William Sinkele, Tulio de Oliveria, David Bukusi, John Scott, Carey Farquhar, Joshua T Herbeck","doi":"10.1093/ve/veae092","DOIUrl":"10.1093/ve/veae092","url":null,"abstract":"<p><p>Although recent modeling suggests that needle-syringe programs (NSPs) have reduced parenteral HIV transmission among people who inject drugs (PWID) in Kenya, the prevalence in this population remains high (∼14-20%, compared to ∼4% in the larger population). Reducing transmission or acquisition requires understanding historic and modern transmission trends, but the relationship between the PWID HIV-1 sub-epidemic and the general epidemic in Kenya is not well understood. We incorporated 303 new (2018-21) HIV-1 <i>pol</i> sequences from PWID and their sexual and injecting partners with 2666 previously published Kenyan HIV-1 sequences to quantify relative rates and direction of HIV-1 transmissions involving PWID from the coast and Nairobi regions of Kenya. We used genetic similarity cluster analysis (thresholds: patristic distance <0.045 and <0.015) and maximum likelihood and Bayesian ancestral state reconstruction to estimate transmission histories at the population group (female sex workers, men who have sex with men, PWID, or general population) and regional (coast or Nairobi) levels. Of 1081 participants living with HIV-1, 274 (25%) were not virally suppressed and 303 (28%) had sequences available. Of new sequences from PWID, 58% were in phylogenetic clusters at distance threshold <0.045. Only 21% of clusters containing sequences from PWID included a second PWID sequence. Sequences from PWID were similarly likely to cluster with sequences from female sex workers, men who have sex with men, and the general population. Ancestral state reconstruction suggested that transmission to PWID from other populations was more common than from PWID to other populations. This study expands our understanding of the HIV-1 sub-epidemic among PWID in Kenya by incorporating four times more HIV-1 sequences from this population than prior studies. Despite recruiting many PWID from local sexual and injecting networks, we found low levels of linked transmission in this population. This may suggest lower relative levels of parenteral transmission in recent years and supports maintaining NSPs among PWID, while also strengthening interventions to reduce HIV-1 sexual acquisition and transmission for this population.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae092"},"PeriodicalIF":5.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11640816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}