Archival influenza virus genomes from Europe reveal genomic variability during the 1918 pandemic

The 1918 influenza pandemic was the deadliest respiratory pandemic of the 20th century and determined the genomic make-up of subsequent human influenza A viruses (IAV). Here, we analyze both the first 1918 IAV genomes from Europe and the first from samples prior to the autumn peak. 1918 IAV genomic diversity is consistent with a combination of local transmission and long-distance dispersal events. Comparison of genomes before and during the pandemic peak shows variation at two sites in the nucleoprotein gene associated with resistance to host antiviral response, pointing at a possible adaptation of 1918 IAV to humans. Finally, local molecular clock modeling suggests a pure pandemic descent of seasonal H1N1 IAV as an alternative to the hypothesis of origination through an intrasubtype reassortment

Host ecology determines the dispersal patterns of a plant virus

Since its isolation in 1966 in Kenya, rice yellow mottle virus (RYMV) has been reported throughout Africa resulting in one of the economically most important tropical plant emerging diseases. A thorough understanding of RYMV evolution and dispersal is critical to manage viral spread in tropical areas that heavily rely on agriculture for subsistence. Phylogenetic analyses have suggested a relatively recent expansion, perhaps driven by the intensification of agricultural practices, but this has not yet been examined in a coherent statistical framework. To gain insight into the historical spread of RYMV within Africa rice cultivations, we analyse a dataset of 300 coat protein gene sequences, sampled from East to West Africa over a 46-year period, using Bayesian evolutionary inference. Spatiotemporal reconstructions date the origin of RMYV back to 1852 (1791-1903) and confirm Tanzania as the most likely geographic origin. Following a single long-distance transmission event from East to West Africa, separate viral populations have been maintained for about a century. To identify the factors that shaped the RYMV distribution, we apply a generalised linear model (GLM) extension of discrete phylogenetic diffusion and provide strong support for distances measured on a rice connectivity landscape as the major determinant of RYMV spread. Phylogeographic estimates in continuous space further complement this by demonstrating more pronounced expansion dynamics in West Africa that are consistent with agricultural intensification and extensification. Taken together, our principled phylogeographic inference approach shows for the first time that host ecology dynamics have shaped the historical spread of a plant virus.status: publishe

Limited evolution of the yellow fever virus 17d in a mouse infection model.

By infecting mice with the yellow fever virus vaccine strain 17D (YFV-17D; Stamaril®), the dose dependence and evolutionary consequences of neurotropic yellow fever infection was assessed. Highly susceptible AG129 mice were used to allow for a maximal/unlimited expansion of the viral populations. Infected mice uniformly developed neurotropic disease; the virus was isolated from their brains, plaque purified and sequenced. Viral RNA populations were overall rather homogenous [Shannon entropies 0-0.15]. The remaining, yet limited intra-host population diversity (0-11 nucleotide exchanges per genome) appeared to be a consequence of pre-existing clonal heterogeneities (quasispecies) of Stamaril®. In parallel, mice were infected with a molecular clone of YFV-17D which was in vivo launched from a plasmid. Such plasmid-launched YFV-17D had a further reduced and almost clonal evolution. The limited intra-host evolution during unrestricted expansion in a highly susceptible host is relevant for vaccine and drug development against flaviviruses in general. Firstly, a propensity for limited evolution even upon infection with a (very) low inoculum suggests that fractional dosing as implemented in current YF-outbreak control may pose only a limited risk of reversion to pathogenic vaccine-derived virus variants. Secondly, it also largely lowers the chance of antigenic drift and development of resistance to antivirals

Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption

Background: Validated biomarkers to evaluate HIV-1 cure strategies are currently lacking, therefore requiring analytical treatment interruption (ATI) in study participants. Little is known about the safety of ATI and its long-term impact on patient health. Objectives: ATI safety was assessed and potential biomarkers predicting viral rebound were evaluated. Methods: PBMCs, plasma and CSF were collected from 11 HIV-1-positive individuals at four different timepoints during ATI (NCT02641756). Total and integrated HIV-1 DNA, cell-associated (CA) HIV-1 RNA transcripts and restriction factor (RF) expression were measured by PCR-based assays. Markers of neuroinflammation and neuronal injury [neurofilament light chain (NFL) and YKL-40 protein] were measured in CSF. Additionally, neopterin, tryptophan and kynurenine were measured, both in plasma and CSF, as markers of immune activation. Results: Total HIV-1 DNA, integrated HIV-1 DNA and CA viral RNA transcripts did not differ pre- and post-ATI. Similarly, no significant NFL or YKL-40 increases in CSF were observed between baseline and viral rebound. Furthermore, markers of immune activation did not increase during ATI. Interestingly, the RFs SLFN11 and APOBEC3G increased after ATI before viral rebound. Similarly, Tat-Rev transcripts were increased preceding viral rebound after interruption. Conclusions: ATI did not increase viral reservoir size and it did not reveal signs of increased neuronal injury or inflammation, suggesting that these well-monitored ATIs are safe. Elevation of Tat-Rev transcription and induced expression of the RFs SLFN11 and APOBEC3G after ATI, prior to viral rebound, indicates that these factors could be used as potential biomarkers predicting viral rebound

Reconstruction of the origin and dispersal of the worldwide dominant Hepatitis B Virus subgenotype D1

Funding Information: N.S.T. and P.L. were supported by the European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement number 278433-PREDEMICS. The research leading to these results has received funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422 - ReservoirDOCS). MT is a PhD fellow at the Research Foundation Flanders (FWO, Belgium, grant number 1S47118N). A.-C.P.-P. was supported by European Funds through grant 'Bio-Molecular and Epidemiological Surveillance of HIV Transmitted Drug Resistance, Hepatitis Co- Infections and Ongoing Transmission Patterns in Europe' (BEST HOPE) (project funded through HIVERA: Harmonizing Integrating Vitalizing European Research on HIV/Aids, grant 249697); by Fundação para a Cieñcia e Tecnologia for funds to GHTMUID/ Multi/04413/2013; by the Migrant HIV project (financed by FCT: PTDC/DTP-EPI/7066/2014; and by Gilead Ǵenese HIVLatePresenters. B.V. was supported by a postdoctoral grant (12U7121N) of the FWO (Fonds Wetenschappelijk Onderzoek - Vlaanderen). G.B. acknowledges support from the Interne Fondsen KU Leuven/ Internal Funds KU Leuven under grant agreement C14/18/094 and the Research Foundation - Flanders ('Fonds voor Wetenschappelijk Onderzoek - Vlaanderen', G0E1420N, G098321N). This work was supported by the Bijzonder Onderzoeksfonds KU Leuven (BOF) No. OT/14/115. This work was supported by public grants. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022 The Author(s).Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV-D1 is the dominant subgenotype in the Mediterranean basin, Eastern Europe, and Asia. However, little is currently known about its evolutionary history and spatio-temporal dynamics. We use Bayesian phylodynamic inference to investigate the temporal history of HBV-D1, for which we calibrate the molecular clock using ancient sequences, and reconstruct the viral global spatial dynamics based, for the first time, on full-length publicly available HBV-D1 genomes from a wide range of sampling dates. We pinpoint the origin of HBV subgenotype D1 before the current era (BCE) in Turkey/Anatolia. The spatial reconstructions reveal global viral transmission with a high degree of mixing. By combining modern-day and ancient sequences, we ensure sufficient temporal signal in HBV-D1 data to enable Bayesian phylodynamic inference using a molecular clock for time calibration. Our results shed light on the worldwide HBV-D1 epidemics and suggest that this originally Middle Eastern virus significantly affects more distant countries, such as those in mainland Europe.publishersversionpublishe

the Portuguese case

BACKGROUND: Portugal has one of the most severe HIV-1 epidemics in Western Europe. Two subtypes circulate in parallel since the beginning of the epidemic. Comparing their transmission patterns and its association with transmitted drug resistance (TDR) is important to pinpoint transmission hotspots and to develop evidence-based treatment guidelines. METHODS: Demographic, clinical and genomic data were collected from 3599 HIV-1 naive patients between 2001 and 2014. Sequences obtained from drug resistance testing were used for subtyping, TDR determination and transmission clusters (TC) analyses. RESULTS: In Portugal, transmission of subtype B was significantly associated with young males, while transmission of subtype G was associated with older heterosexuals. In Portuguese originated people, there was a decreasing trend both for prevalence of subtype G and for number of TCs in this subtype. The active TCs that were identified (i.e. clusters originated after 2008) were associated with subtype B-infected males residing in Lisbon. TDR was significantly different when comparing subtypes B (10.8% [9.5-12.2]) and G (7.6% [6.4-9.0]) (p = 0.001). DISCUSSION: TC analyses shows that, in Portugal, the subtype B epidemic is active and fueled by young male patients residing in Lisbon, while transmission of subtype G is decreasing. Despite similar treatment rates for both subtypes in Portugal, TDR is significantly different between subtypes.publishersversionpublishe

Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy

Background: In-depth phylogeographic analysis can reveal migration patterns relevant for public health planning. Here, as a model, we focused on the provenance, in the current Italian HCV subtype 1a epidemic, of the NS3 resistance-associated variant (RAV) Q80K, known to interfere with the action of NS3/4A protease inhibitor simeprevir. HCV1a migration patterns were analysed using Bayesian phylodynamic tools, capitalising on newly generated and publicly available time and geo-referenced NS3 encoding virus genetic sequence data. Results: Our results showed that both immigration and local circulation fuel the current Italian HCV1a epidemic. The United States and European continental lineages dominate import into Italy, with the latter taking the lead from the 1970s onwards. Since similar migration patterns were found for Q80K and other lineages, no clear differentiation of the risk for failing simeprevir can be made between patients based on their migration and travel history. Importantly, since HCV only occasionally recombines, these results are readily transferable to the genetic sequencing policy concerning NS5A RAVs. Conclusions: The patient migration and travel history cannot be used to target only part of the HCV1a infected population for drug resistance testing before start of antiviral therapy. Consequently, it may be cost-effective to expand genotyping efforts to all HCV1a infected patients eligible for simeprevir-based therapies. © 2017 The Author(s)

Archival influenza virus genomes from Europe reveal genomic variability during the 1918 pandemic

The 1918 influenza pandemic was the deadliest respiratory pandemic of the 20th century and determined the genomic make-up of subsequent human influenza A viruses (IAV). Here, we analyze both the first 1918 IAV genomes from Europe and the first from samples prior to the autumn peak. 1918 IAV genomic diversity is consistent with a combination of local transmission and long-distance dispersal events. Comparison of genomes before and during the pandemic peak shows variation at two sites in the nucleoprotein gene associated with resistance to host antiviral response, pointing at a possible adaptation of 1918 IAV to humans. Finally, local molecular clock modeling suggests a pure pandemic descent of seasonal H1N1 IAV as an alternative to the hypothesis of origination through an intrasubtype reassortment.Peer Reviewe