Welcome to the IUMS 2022 Interactive Program

Abstract Body

Advances in sequencing technologies have allowed the scientific exploration of museum specimens, opening vast arrays of applications grounded in the evolutionary analyses of these genomes. The origin of infectious diseases, including viral diseases, also profit from such efforts. In this presentation, I will present how museomics, coupled with a robust phylodynamic inference framework, triggered a re-analysis of the origin of measles [Düx, Lequime, et al. 2020 Science]. We used a virus genome from a fatal measles case from 1912 in Berlin (Germany), and a molecular clock model that accounts for various sources of rate heterogeneity and long-term purifying selection implemented in a Bayesian phylogenetic framework (BEAST). Our analyses push back the emergence of the measles lineage to Antiquity, around the 6th century BC. Interestingly, this overlaps with the upsurge in population size of human communities both in the Western and Far-Eastern world, which may have reached the critical level needed to maintain the virus during this period.

More recently, we used a similar approach to explore the dynamics of the 1918 influenza virus pandemic [Patrono, Vranken, Budt, et al. 2022 Nature Communications]. These results highlight the importance of medical collections in genomic research and plead for dedicating resources to preserving these valuable specimens and associated written sources.

Background and Aims

Yam (Dioscorea spp) is an important staple crop for hundreds of millions of people in the tropics and subtropics. Its production is increasingly threatened by pests and pathogens, including viruses whose prevalence, epidemiology and routes of invasion remain largely unknown, precluding the implementation of efficient control strategies.

Methods

Targeting Guadeloupe, a Caribbean island and yam diversification hotspot, we undertook the first large-scale epidemiological study of 13 yam viruses and addressed key issues such as their molecular diversity and entry pathways in Guadeloupe, and the recontamination dynamics of sanitised yam plants under field conditions.

Results

Our results showed that most yam plants are co-infected by up to 5 distinct viruses and that the structuration of the molecular diversity of the viruses targeted by this study differs between viruses. These results also provide insights into the role of weeds as reservoirs of yam viruses and the potential of weed management to better control these viruses. We showed that import of yam tubers for human consumption promotes the introduction of viruses in Guadeloupe, and potentially in other tropical islands with fragile agro-ecosystems. Finally, we showed that plots of fully sanitized yam plants were almost entirely infected after only two consecutive years, and that infection rates differed widely among viruses.

Conclusions

Overall, our results open the way to the implementation of a comprehensive strategy for controlling yam viruses in Guadeloupe and in other similar tropical island agroecosystems.

Background and Aims

Polyomavirus JC (JCPyV) is ubiquitous and is the causative agent for Progessive Multifocal Leucoencephalopathy (PML), a rare disease that occurs in immunocompromised hosts (mostly in HIV patients). There are described eight genotypes which are strongly related to geographical areas: 1 and 4 (Europe), 2 and 7 (Asia), 3 and 6 (Africa) and 8 P.N.Guinea and Pacific Islands. The first population to settle in the Americas, brought with them type 2A from northeast Asia. The aim of this study was to describe the characteristics of JCPyV positive patients and the genotypes of the strains detected between 2006 and 2021.

Methods

A Nested-PCR in cerebrospinal fluid was carried out for diagnosis, then sequence analysis was performed using JCPyV-specific primers designed against VP1 (Torres2016). Samples from 1267 patients with presumptive LMP were processed.

Results

Eleven percent (n=137) tested positive for JCPyV. Ninety-nine percent were HIV+ and the age was 19-67 years old (media 39).The time from onset of symptoms was higher than 4 weeks in 71% of the cases, 68% were under HAART, CD4+ count was 114 cel/mm³ and HIV viral load 5,9 log₁₀ copies/ml in average, respectively. VP1 gene sequences were obtained from 32 samples that were selected to cover all the period. Phylogenetic analyses indicated that they belonged to genotypes 2 A (n=23), 1 (n=7), 3 (n=1) and 4 (n=1).

Conclusions

Positive cases were related to VIH advanced disease and long time of convalescence. The genotypes that we found seem to be more related to the geographical area than to the pathogenesis of the virus.

Background and Aims

Majority of chronic hepatitis C virus (HCV) infections in Europe are caused by genotype 1 which has disseminated globally during the 20th century. High prevalence of subtype 1a is observed in Croatian patients, especially among intravenous drug users (IDU). The aim of this study was to investigate epidemic history of the HCV subtype 1a in Croatian population.

Methods

The study included 109 patients at the University Hospital for Infectious Diseases Zagreb infected with HCV subtype 1a from 2016 to 2019. Time-stamped NS3, NS5A and NS5B sequences of each patient were concatenated and phylodynamic analysis was performed using Bayesian Markov Chain Monte Carlo approach implemented in BEAST v.2.6. Models of population growth and molecular clock were selected based on Bayes factor analysis.

Results

Bayes factor analysis favored the relaxed lognormal molecular clock and the Bayesian skyline demographic model. The mean estimated substitution rate of the subtype 1a was 1.48 × 10^-3 (HPD95%, 0.52 – 2.40 × 10^-3), while the mean estimate for the time to most recent common ancestor was 59 years (HPD95%, 25 – 108) (Table 1). The Bayesian skyline analysis revealed an exponential increase in HCV subtype 1a infections from 1990s onwards (Figure 1).

Conclusions

The increase of HCV subtype 1a in the 1990s and its continued growth throughout the first decade of the 2000s is in accordance with a huge increase in the number of IDU registered in this period in Croatia. Establishment of harm reduction programs could have contributed to stabilization of HCV subtype 1a incidence in the last decade.

Background and Aims

A full understanding of the genomic and phenotypic changes of RNA viruses across epidemics has become critically important. Two important questions are: (1) under what epidemiological conditions are virus variants preferentially selected to increase epidemic severity at later time periods in epidemics or pandemics; and (2) what are the impacts of different public health prevention and control strategies on viral changes?

Methods

DENV-2-specific cDNA flanking the E gene were deep sequenced to compare quasispecies. Antibody responses to H1N1(H1N1/pdm09)-HA1-E374K mutants and replication efficiency of the two duck influenza viruses with amino acid variations in both chicken DF1 and MDCK cells were evaluated. Recently, we used the viral sequence analysis tools that we had developed in-house to integrate epidemiological characteristics with the SARS-CoV-2 sequences from the Alpha variant, which caused a 2021 outbreak in northern Taiwan.

Results

Different virus variants did appear through a series of human-to-human transmission chains with various spatio-temporal population dynamics. The over-wintering DENV-2 variants with lower genetic diversity, transmission rate, and intra-host variant numbers might play an important role in over-wintering, maintaining viral variants, and causing more severe epidemics. The H1N1/pdm09)-HA1-E374K mutant ultimately emerged as the dominant strain in high population-dense areas, and then persisted regardless of all intervention measures. The dominant SARS-CoV-2 Alpha variant did emerge from high population-density districts in Taipei and New Taipei Cities, but showed a declining trend after the implementation of a rigorous Level 3 Alert Control Policy.

Conclusions

The integration of phylodynamic and deep sequencing analysis can be very useful for public health surveillance.