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Lewis NS, Russell CA, Langat P, et al., 2016, The global antigenic diversity of swine influenza A viruses, eLife, Vol: 5, ISSN: 2050-084X
Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds complexity to the risk profiles for the movement of swine and the potential for swine-derived infections in humans.
Munnink BBO, My VTP, Kellam P, et al., 2016, Complete genome characterization of two wild-type measles viruses from Vietnamese infants during the 2014 outbreak, Microbiology Resource Announcements, Vol: 4, ISSN: 2576-098X
A large measles virus outbreak occurred across Vietnam in 2014. We identified and obtained complete measles virus genomes in stool samples collected from two diarrheal pediatric patients in Dong Thap Province. These are the first complete genome sequences of circulating measles viruses in Vietnam during the 2014 measles outbreak.
Mee ET, Preston MD, Participant CSSS, et al., 2016, Development of a candidate reference material for adventitious virus detection in vaccine and biologicals manufacturing by deep sequencing, Vaccine, Vol: 34, Pages: 2035-2043, ISSN: 0264-410X
BackgroundUnbiased deep sequencing offers the potential for improved adventitious virus screening in vaccines and biotherapeutics. Successful implementation of such assays will require appropriate control materials to confirm assay performance and sensitivity.MethodsA common reference material containing 25 target viruses was produced and 16 laboratories were invited to process it using their preferred adventitious virus detection assay.ResultsFifteen laboratories returned results, obtained using a wide range of wet-lab and informatics methods. Six of 25 target viruses were detected by all laboratories, with the remaining viruses detected by 4–14 laboratories. Six non-target viruses were detected by three or more laboratories.ConclusionThe study demonstrated that a wide range of methods are currently used for adventitious virus detection screening in biological products by deep sequencing and that they can yield significantly different results. This underscores the need for common reference materials to ensure satisfactory assay performance and enable comparisons between laboratories.
Dialdestoro K, Sibbesen JA, Maretty L, et al., 2016, Coalescent Inference Using Serially Sampled, High-Throughput Sequencing Data from Intrahost HIV Infection, GENETICS, Vol: 202, Pages: 1449-+, ISSN: 0016-6731
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- Citations: 6
Munnink BBO, Cotten M, Canuti M, et al., 2016, A novel astrovirus-like RNA virus detected in human stool, Virus Evolution, Vol: 2, ISSN: 2057-1577
Several novel clades of astroviruses have recently been identified in human faecal samples. Here, we describe a novel astrovirus-like RNA virus detected in human stools, which we have tentatively named bastrovirus. The genome of this novel virus consists of 6,300 nucleotides organized in three open reading frames. Several sequence divergent strains were detected sharing 67–93 per cent nucleotide identity. Bastrovirus encodes a putative structural protein that is homologous to the capsid protein found in members of the Astroviridae family (45% amino acid identity). The virus also encodes a putative non-structural protein that is genetically distant from astroviruses but shares some homology to the non-structural protein encoded by members of the Hepeviridae family (28% amino acid identity). This novel bastrovirus is present in 8.7 per cent (35/400) of faecal samples collected from 300 HIV-1-positive and 100 HIV-1-negative individuals suggesting common occurrence of the virus. However, whether the source of the virus is infected human cells or other, for example, dietary, remains to be determined.
Arias A, Watson SJ, Asogun D, et al., 2016, Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases, Virus Evolution, Vol: 2, ISSN: 2057-1577
To end the largest known outbreak of Ebola virus disease (EVD) in West Africa and to prevent new transmissions, rapid epidemiological tracing of cases and contacts was required. The ability to quickly identify unknown sources and chains of transmission is key to ending the EVD epidemic and of even greater importance in the context of recent reports of Ebola virus (EBOV) persistence in survivors. Phylogenetic analysis of complete EBOV genomes can provide important information on the source of any new infection. A local deep sequencing facility was established at the Mateneh Ebola Treatment Centre in central Sierra Leone. The facility included all wetlab and computational resources to rapidly process EBOV diagnostic samples into full genome sequences. We produced 554 EBOV genomes from EVD cases across Sierra Leone. These genomes provided a detailed description of EBOV evolution and facilitated phylogenetic tracking of new EVD cases. Importantly, we show that linked genomic and epidemiological data can not only support contact tracing but also identify unconventional transmission chains involving body fluids, including semen. Rapid EBOV genome sequencing, when linked to epidemiological information and a comprehensive database of virus sequences across the outbreak, provided a powerful tool for public health epidemic control efforts.
Simon G, Larsen LE, Dürrwald R, et al., 2015, European surveillance network for influenza in pigs: surveillance programs, diagnostic tools and Swine influenza virus subtypes identified in 14 European countries from 2010 to 2013, PLoS ONE, Vol: 9, ISSN: 1932-6203
Swine influenza causes concern for global veterinary and public health officials. In continuing two previous networks that initiated the surveillance of swine influenza viruses (SIVs) circulating in European pigs between 2001 and 2008, a third European Surveillance Network for Influenza in Pigs (ESNIP3, 2010-2013) aimed to expand widely the knowledge of the epidemiology of European SIVs. ESNIP3 stimulated programs of harmonized SIV surveillance in European countries and supported the coordination of appropriate diagnostic tools and subtyping methods. Thus, an extensive virological monitoring, mainly conducted through passive surveillance programs, resulted in the examination of more than 9 000 herds in 17 countries. Influenza A viruses were detected in 31% of herds examined from which 1887 viruses were preliminary characterized. The dominating subtypes were the three European enzootic SIVs: avian-like swine H1N1 (53.6%), human-like reassortant swine H1N2 (13%) and human-like reassortant swine H3N2 (9.1%), as well as pandemic A/H1N1 2009 (H1N1pdm) virus (10.3%). Viruses from these four lineages co-circulated in several countries but with very different relative levels of incidence. For instance, the H3N2 subtype was not detected at all in some geographic areas whereas it was still prevalent in other parts of Europe. Interestingly, H3N2-free areas were those that exhibited highest frequencies of circulating H1N2 viruses. H1N1pdm viruses were isolated at an increasing incidence in some countries from 2010 to 2013, indicating that this subtype has become established in the European pig population. Finally, 13.9% of the viruses represented reassortants between these four lineages, especially between previous enzootic SIVs and H1N1pdm. These novel viruses were detected at the same time in several countries, with increasing prevalence. Some of them might become established in pig herds, causing implications for zoonotic infections.
Gallo Cassarino T, Frampton D, Sugar R, et al., 2015, High-throughput pipeline for the <i>de novo</i> viral genome assembly and the identification ofminority variants from Next-Generation Sequencing of residual diagnostic samples
<jats:title>Abstract</jats:title><jats:sec><jats:title>Motivation</jats:title><jats:p>The underlying genomic variation of a large number of pathogenic viruses can give rise to drug resistant mutations resulting in treatment failure. Next generation sequencing (NGS) enables the identification of viral quasi-species and the quantification of minority variants in clinical samples; therefore, it can be of direct benefit by detecting drug resistant mutations and devising optimal treatment strategies for individual patients.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The ICONIC (InfeCtion respONse through vIrus genomiCs) project has developed an automated, portable and customisable high-throughput computational pipeline to assemble <jats:italic>de novo</jats:italic> whole viral genomes, either segmented or non-segmented, and quantify minority variants using residual diagnostic samples. The pipeline has been benchmarked on a dedicated High-Performance Computing cluster using paired-end reads from RSV and Influenza clinical samples. The median length of generated genomes was 96% for the RSV dataset and 100% for each Influenza segment. The analysis of each set lasted less than 12 hours; each sample took around 3 hours and required a maximum memory of 10 GB. The pipeline can be easily ported to a dedicated server or cluster through either an installation script or a docker image. As it enables the subtyping of viral samples and the detection of relevant drug resistance mutations within three days of sample collection, our pipeline could operate within existing clinical reporting time frames and potentially be used as a decision support tool towards more effective personalised patient treatments.</jats:p></jats:sec><jats:sec><jats:title>Availability</jats:title><jats:p>The software and its documentation are available from <jats:ex
Rabaa MA, Ngo TT, Tran MP, et al., 2015, The Vietnam Initiative on Zoonotic Infections (VIZIONS): A strategic approach to studying emerging zoonotic infectious diseases, EcoHealth, Vol: 12, Pages: 726-735, ISSN: 1076-2825
The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to
Stacey MA, Clare S, Marsden M, et al., 2015, IFITM3 restricts virus-induced pathogenesis by regulating myeloid cell production of interleukin-6, 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society (ICIS), Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, Pages: 96-96, ISSN: 1043-4666
Watson SJ, Langat P, Reid SM, et al., 2015, Molecular epidemiology and evolution of influenza viruses circulating within European swine between 2009 and 2013, Journal of Virology, Vol: 89, Pages: 9920-9931, ISSN: 1098-5514
The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. To date, large-scale surveillance studies have been reported for southern China and North America, but such data have not yet been described for Europe. We report the first large-scale genomic characterization of 290 swine influenza viruses collected from 14 European countries between 2009 and 2013. A total of 23 distinct genotypes were identified, with the 7 most common comprising 82% of the incidence. Contrasting epidemiological dynamics were observed for two of these genotypes, H1huN2 and H3N2, with the former showing multiple long-lived geographically isolated lineages, while the latter had short-lived geographically diffuse lineages. At least 32 human-swine transmission events have resulted in A(H1N1)pdm09 becoming established at a mean frequency of 8% across European countries. Notably, swine in the United Kingdom have largely had a replacement of the endemic Eurasian avian virus-like (“avian-like”) genotypes with A(H1N1)pdm09-derived genotypes. The high number of reassortant genotypes observed in European swine, combined with the identification of a genotype similar to the A(H3N2)v genotype in North America, underlines the importance of continued swine surveillance in Europe for the purposes of maintaining public health. This report further reveals that the emergences and drivers of virus evolution in swine differ at the global level.
Munnink BBO, Cotten M, Deijs M, et al., 2015, A novel genus in the order <i>Picornavirales</i> detected in human stool, JOURNAL OF GENERAL VIROLOGY, Vol: 96, Pages: 3440-3443, ISSN: 0022-1317
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- Citations: 21
Woolhouse MEJ, Rambaut A, Kellam P, 2015, Lessons from Ebola: Improving infectious disease surveillance to inform outbreak management, SCIENCE TRANSLATIONAL MEDICINE, Vol: 7, ISSN: 1946-6234
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- Citations: 65
Hoehn KB, Gall A, Bashford-Rogers R, et al., 2015, Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436
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- Citations: 19
Mbisa JL, Fearnhill E, Dunn DT, et al., 2015, Evidence of Self-Sustaining Drug Resistant HIV-1 Lineages Among Untreated Patients in the United Kingdom, CLINICAL INFECTIOUS DISEASES, Vol: 61, Pages: 829-836, ISSN: 1058-4838
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- Citations: 31
Jose S, Quinn K, Dunn D, et al., 2015, Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation, HIV Medicine, Vol: 17, Pages: 368-372, ISSN: 1464-2662
ObjectivesNo randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development.MethodsIn a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART.ResultsOf 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL.ConclusionsWe found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL.
Nomikou K, Hughes J, Wash R, et al., 2015, Widespread reassortment shapes the evolution and epidemiology of bluetongue virus following European invasion, PLoS Pathogens, Vol: 11, ISSN: 1553-7366
Genetic exchange by a process of genome-segment ‘reassortment’ represents an important mechanism for evolutionary change in all viruses with segmented genomes, yet in many cases a detailed understanding of its frequency and biological consequences is lacking. We provide a comprehensive assessment of reassortment in bluetongue virus (BTV), a globally important insect-borne pathogen of livestock, during recent outbreaks in Europe. Full-genome sequences were generated and analysed for over 150 isolates belonging to the different BTV serotypes that have emerged in the region over the last 5 decades. Based on this novel dataset we confirm that reassortment is a frequent process that plays an important and on-going role in evolution of the virus. We found evidence for reassortment in all ten segments without a significant bias towards any particular segment. However, we observed biases in the relative frequency at which particular segments were associated with each other during reassortment. This points to selective constraints possibly caused by functional relationships between individual proteins or genome segments and genome-wide epistatic interactions. Sites under positive selection were more likely to undergo amino acid changes in newly reassorted viruses, providing additional evidence for adaptive dynamics as a consequence of reassortment. We show that the live attenuated vaccines recently used in Europe have repeatedly reassorted with field strains, contributing to their genotypic, and potentially phenotypic, variability. The high degree of plasticity seen in the BTV genome in terms of segment origin suggests that current classification schemes that are based primarily on serotype, which is determined by only a single genome segment, are inadequate. Our work highlights the need for a better understanding of the mechanisms and epidemiological consequences of reassortment in BTV, as well as other segmented RNA viruses.
Hunt M, Gall A, Ong SH, et al., 2015, IVA: accurate de novo assembly of RNA virus genomes, Bioinformatics, Vol: 31, Pages: 2374-2376, ISSN: 1367-4803
Motivation: An accurate genome assembly from short read sequencing data is critical for downstream analysis, for example allowing investigation of variants within a sequenced population. However, assembling sequencing data from virus samples, especially RNA viruses, into a genome sequence is challenging due to the combination of viral population diversity and extremely uneven read depth caused by amplification bias in the inevitable reverse transcription and polymerase chain reaction amplification process of current methods.Results: We developed a new de novo assembler called IVA (Iterative Virus Assembler) designed specifically for read pairs sequenced at highly variable depth from RNA virus samples. We tested IVA on datasets from 140 sequenced samples from human immunodeficiency virus-1 or influenza-virus-infected people and demonstrated that IVA outperforms all other virus de novo assemblers.Availability and implementation: The software runs under Linux, has the GPLv3 licence and is freely available from http://sanger-pathogens.github.io/iva
Wilflingseder D, Schroll A, Hackl H, et al., 2015, Immediate T-Helper 17 Polarization Upon Triggering CD11b/c on HIV-Exposed Dendritic Cells, JOURNAL OF INFECTIOUS DISEASES, Vol: 212, Pages: 44-56, ISSN: 0022-1899
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- Citations: 14
Brener J, Gall A, Batorsky R, et al., 2015, Disease progression despite protective HLA expression in an HIV-infected transmission pair, Retrovirology, Vol: 12, ISSN: 1742-4690
BackgroundThe precise immune responses mediated by HLA class I molecules such as HLA-B*27:05 and HLA-B*57:01 that protect against HIV disease progression remain unclear. We studied a CRF01_AE clade HIV infected donor-recipient transmission pair in which the recipient expressed both HLA-B*27:05 and HLA-B*57:01.ResultsWithin 4.5 years of diagnosis, the recipient had progressed to meet criteria for antiretroviral therapy initiation. We employed ultra-deep sequencing of the full-length virus genome in both donor and recipient as an unbiased approach by which to identify specific viral mutations selected in association with progression. Using a heat map method to highlight differences in the viral sequences between donor and recipient, we demonstrated that the majority of the recipient’s mutations outside of Env were within epitopes restricted by HLA-B*27:05 and HLA-B*57:01, including the well-studied Gag epitopes. The donor, who also expressed HLA alleles associated with disease protection, HLA-A*32:01/B*13:02/B*14:01, showed selection of mutations in parallel with disease progression within epitopes restricted by these protective alleles.ConclusionsThese studies of full-length viral sequences in a transmission pair, both of whom expressed protective HLA alleles but nevertheless failed to control viremia, are consistent with previous reports pointing to the critical role of Gag-specific CD8+ T cell responses restricted by protective HLA molecules in maintaining immune control of HIV infection. The transmission of subtype CRF01_AE clade infection may have contributed to accelerated disease progression in this pair as a result of clade-specific sequence differences in immunodominant epitopes.
Dialdestoro K, Sibbesen JA, Maretty L, et al., 2015, Coalescent inference using serially sampled, high-throughput sequencing data from intra-host HIV infection
<jats:title>ABSTRACT</jats:title><jats:p>Human immunodeficiency virus (HIV) is a rapidly evolving pathogen that causes chronic infections, so genetic diversity within a single infection can be very high. High-throughput “deep” sequencing can now measure this diversity in unprecedented detail, particularly since it can be performed at different timepoints during an infection, and this offers a potentially powerful way to infer the evolutionary dynamics of the intra-host viral population. However, population genomic inference from HIV sequence data is challenging because of high rates of mutation and recombination, rapid demographic changes, and ongoing selective pressures. In this paper we develop a new method for inference using HIV deep sequencing data using an approach based on importance sampling of ancestral recombination graphs under a multi-locus coalescent model. The approach further extends recent progress in the approximation of so-called<jats:italic>conditional sampling distributions</jats:italic>, a quantity of key interest when approximating co-alescent likelihoods. The chief novelties of our method are that it is able to infer rates of recombination and mutation, as well as the effective population size, while handling sampling over different timepoints and missing data without extra computational difficulty. We apply our method to a dataset of HIV-1, in which several hundred sequences were obtained from an infected individual at seven timepoints over two years. We find mutation rate and effective population size estimates to be comparable to those produced by the software BEAST. Additionally, our method is able to produce local recombination rate estimates. The software underlying our method, Coalescenator, is freely available.</jats:p>
Hill SC, Murphy AA, Cotten M, et al., 2015, Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae, Journal of General Virology, Vol: 96, Pages: 1411-1422, ISSN: 0022-1317
Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups.
Benfield CTO, Smith SE, Wright E, et al., 2015, Bat and pig IFN-induced transmembrane protein 3 restrict cell entry by influenza virus and lyssaviruses, Journal of General Virology, Vol: 96, Pages: 991-1005, ISSN: 1465-2099
IFN-induced transmembrane protein 3 (IFITM3) is a restriction factor that blocks cytosolic entry of numerous viruses that utilize acidic endosomal entry pathways. In humans and mice, IFITM3 limits influenza-induced morbidity and mortality. Although many IFITM3-sensitive viruses are zoonotic, whether IFITMs function as antiviral restriction factors in mammalian species other than humans and mice is unknown. Here, IFITM3 orthologues in the microbat (Myotis myotis) and pig (Sus scrofa domesticus) were identified using rapid amplification of cDNA ends. Amino acid residues known to be important for IFITM3 function were conserved in the pig and microbat orthologues. Ectopically expressed pig and microbat IFITM3 co-localized with transferrin (early endosomes) and CD63 (late endosomes/multivesicular bodies). Pig and microbat IFITM3 restricted cell entry mediated by multiple influenza haemagglutinin subtypes and lyssavirus glycoproteins. Expression of pig or microbat IFITM3 in A549 cells reduced influenza virus yields and nucleoprotein expression. Conversely, small interfering RNA knockdown of IFITM3 in pig NPTr cells and primary microbat cells enhanced virus replication, demonstrating that these genes are functional in their species of origin at endogenous levels. In summary, we showed that IFITMs function as potent broad-spectrum antiviral effectors in two mammals – pigs and bats – identified as major reservoirs for emerging viruses.
Palser AL, Grayson NE, White RE, et al., 2015, Genome Diversity of Epstein-Barr Virus from Multiple Tumor Types and Normal Infection, Journal of Virology, Vol: 89, Pages: 5222-5237, ISSN: 1098-5514
Epstein-Barr virus (EBV) infects most of the world’s population and is causally associated with several human cancers, but littleis known about how EBV genetic variation might influence infection or EBV-associated disease. There are currently no publishedwild-type EBV genome sequences from a healthy individual and very few genomes from EBV-associated diseases. We havesequenced 71 geographically distinct EBV strains from cell lines, multiple types of primary tumor, and blood samples and thefirst EBV genome from the saliva of a healthy carrier. We show that the established genome map of EBV accurately represents allstrains sequenced, but novel deletions are present in a few isolates. We have increased the number of type 2 EBV genomes sequencedfrom one to 12 and establish that the type 1/type 2 classification is a major feature of EBV genome variation, definedalmost exclusively by variation of EBNA2 and EBNA3 genes, but geographic variation is also present. Single nucleotide polymorphism(SNP) density varies substantially across all known open reading frames and is highest in latency-associated genes. SomeT-cell epitope sequences in EBNA3 genes show extensive variation across strains, and we identify codons under positive selection,both important considerations for the development of vaccines and T-cell therapy. We also provide new evidence for recombinationbetween strains, which provides a further mechanism for the generation of diversity. Our results provide the firstglobal view of EBV sequence variation and demonstrate an effective method for sequencing large numbers of genomes to furtherunderstand the genetics of EBV infection.
Agoti CN, Otieno JR, Munywoki PK, et al., 2015, Local evolutionary patterns of human respiratory syncytial virus derived from whole-genome sequencing, Journal of Virology, Vol: 89, Pages: 3444-3454, ISSN: 1098-5514
Human respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies.
Houldcroft CJ, Kellam P, 2015, Host genetics of Epstein-Barr virus infection, latency and disease, Reviews in Medical Virology, Vol: 25, Pages: 71-84, ISSN: 1052-9276
Epstein–Barr virus (EBV) infects 95% of the adult population and is the cause of infectious mononucleosis. It is also associated with 1% of cancers worldwide, such as nasopharyngeal carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma. Human and cancer genetic studies are now major forces determining gene variants associated with many cancers, including nasopharyngeal carcinoma and Hodgkin's lymphoma. Host genetics is also important in infectious disease; however, there have been no large‐scale efforts towards understanding the contribution that human genetic variation plays in primary EBV infection and latency. This review covers 25 years of studies into host genetic susceptibility to EBV infection and disease, from candidate gene studies, to the first genome‐wide association study of EBV antibody response, and an EBV‐status stratified genome‐wide association study of Hodgkin's lymphoma. Although many genes are implicated in EBV‐related disease, studies are often small, not replicated or followed up in a different disease. Larger, appropriately powered genomic studies to understand the host response to EBV will be needed to move our understanding of the biology of EBV infection beyond the handful of genes currently identified. Fifty years since the discovery of EBV and its identification as a human oncogenic virus, a glimpse of the future is shown by the first whole‐genome and whole‐exome studies, revealing new human genes at the heart of the host–EBV interaction.
Pillay D, Herbeck J, Cohen MS, et al., 2015, PANGEA-HIV: phylogenetics for generalised epidemics in Africa, LANCET INFECTIOUS DISEASES, Vol: 15, Pages: 259-261, ISSN: 1473-3099
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- Citations: 40
Farsani SMJ, Munnink BBO, Canuti M, et al., 2015, Identification of a novel human rhinovirus C type by antibody capture VIDISCA-454, Viruses, Vol: 7, Pages: 239-251, ISSN: 1999-4915
Causative agents for more than 30 percent of respiratory infections remain unidentified, suggesting that unknown respiratory pathogens might be involved. In this study, antibody capture VIDISCA-454 (virus discovery cDNA-AFLP combined with Roche 454 high-throughput sequencing) resulted in the discovery of a novel type of rhinovirus C (RV-C). The virus has an RNA genome of at least 7054 nt and carries the characteristics of rhinovirus C species. The gene encoding viral protein 1, which is used for typing, has only 81% nucleotide sequence identity with the closest known RV-C type, and, therefore, the virus represents the first member of a novel type, named RV-C54.
Kwok H, Wu CW, Palser AL, et al., 2015, Genomic Diversity of Epstein-Barr Virus Genomes Isolated from Primary Nasopharyngeal Carcinoma Biopsy Samples (vol 88, pg 10662, 2014), JOURNAL OF VIROLOGY, Vol: 89, Pages: 886-886, ISSN: 0022-538X
McCoy LE, Rutten L, Frampton D, et al., 2014, Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1, PLoS Pathogens, Vol: 10, ISSN: 1553-7366
To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.
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