Biology subjects

Muehlemann, B.

Publications and source records attributed to Muehlemann, B..

5 recordsLinked to original sources

bioRxiv2023

Direct comparison of SARS-CoV-2 variant specific neutralizing antibodies in human and hamster sera

Antigenic characterization of newly emerging SARS-CoV-2 variants is important to assess their immune escape and judge the need for future vaccine updates. As exposure histories for human sera become more and more complex, animal sera may provide an alternative for antigenic characterization of new variants. To bridge data obtained from animal sera with human sera, we here analyzed neutralizing antibody titers in human and hamster first infection sera in a highly controlled setting using the same live-virus neutralization assay performed in one laboratory. Using a Bayesian framework, we found that titer fold changes in hamster sera corresponded well to human sera and that hamster sera generally exhibited higher reactivity. Our results indicate that sera from infected hamsters are a good surrogate for the antigenic characterization of new variants.

immunology↗

bioRxiv2023

The landscape of ancient human pathogens in Eurasia from the Stone Age to historical times

Infectious diseases have had devastating impacts on human populations throughout history, but important questions about their origins and past dynamics remain1. To create the first archaeogenetic-based spatiotemporal map of human pathogens, we screened shotgun sequencing data from 1,313 ancient humans covering 37,000 years of Eurasian history. We demonstrate the widespread presence of ancient bacterial, viral and parasite DNA, identifying 5,486 individual hits against 492 species from 136 genera. Among those hits, 3,384 involve known human pathogens2, many of which were detected for the first time in ancient human remains. Grouping the ancient microbial species according to their likely reservoir and type of transmission, we find that most groups are identified throughout the entire sampling period. Intriguingly, zoonotic pathogens are only detected [~]6,500 years ago, peaking [~]5,000 years ago, coinciding with the widespread domestication of livestock3. Our findings provide the first direct evidence that this lifestyle change resulted in an increased infectious disease burden. Importantly, they also suggest that the spread of these pathogens increased substantially during subsequent millenia, coinciding with the pastoralist migrations from the Eurasian Steppe4,5.

evolutionary biology↗

bioRxiv2022

Genetic variability, including gene duplication and deletion, in early sequences from the 2022 European monkeypox outbreak

Genome sequences from 47 monkeypox virus infections detected in a German university virology laboratory were analyzed in context of other sequences from the 2022 outbreak and earlier monkeypox genomes. Identical non-synonymous amino acid changes in six genes and the signature of APOBEC editing match other sequences from the European outbreak. Non-synonymous changes that were present in one to three sequences were found in 34 other genes. In sequences from two lesions of one patient, an 856 nucleotide translocation between genome termini resulted in the duplication of an initial 5 gene, and the disruption or complete deletion of four genes near the 3 genome end. Orthopoxvirus genome rearrangements of this nature are known to confer fitness advantages in the face of selection pressure. This change may therefore represent an early virus adaptation in the novel widespread and sustained human-to-human context of the current monkeypox outbreak.

bioinformatics↗

bioRxiv2020

Whole-Genome Sequences of the Severe Acute Respiratory Syndrome Coronavirus-2 obtained from Romanian patients between March and June of 2020

Impact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019.Competing Interest StatementTim Durfee is an employee of DNASTAR, Inc.View Full Text

bioinformatics↗

bioRxiv2017

Complete assembly of a dengue virus type 3 genome from a recent genotype III clade by metagenomic sequencing of serum

BackgroundMosquito-borne flaviviruses causing diseases such as dengue and Japanese encephalitis are devastating, particularly in the tropics. Although, multiple flaviviruses are known to co-circulate in India, when a patient presents with febrile illness, testing is usually limited to specific pathogens. Unbiased metagenomic sequencing of febrile cases can reveal the presence of multiple pathogens and provide complete genome information. Sequence information, a cornerstone for tracing virus evolution, is relevant for the design of vaccines and therapeutics. In order to assess the usefulness of unbiased metagenomic sequencing for the identification of viruses associated with febrile illness, we sequenced serum from four individuals and plasma from one individual, all hospitalized at a tertiary care centre in South India with severe or prolonged febrile illnesses, together with one healthy control in 2014.\n\nResultsWe identified and assembled a complete dengue virus type 3 (DENV3) sequence from the serum of a case classified as severe dengue. We also found a small number of Japanese encephalitis virus (JEV) sequences in the serum of two adults with febrile illness, including the one who had dengue. Phylogenetic analysis of the dengue sequence indicates that it belongs to a predominantly Asian, DENV3, genotype III clade. It had an estimated divergence time of 13.86 years (95% Highest Posterior Densities 12.94 - 14.83 years) with the closest Indian strain. Amino acid substitutions were present throughout the sequenced genome, including 11 substitutions in the antigenic envelope protein compared to the strain used for the development of the first commercial dengue vaccine. Of these one substitution (E361D) was unique and six were in critical antigenic sites.\n\nConclusionsWe demonstrate that both genome assembly and detection of a low number of viral sequences are possible by unbiased sequencing of clinical material. Complete dengue virus sequence analysis places the sequenced genome in a recent, predominantly Asian clade within genotype III of DENV3. The detection of JEV, an agent not routinely tested in febrile illness in India, warrants further analysis and highlights the need to study co-circulating flaviviruses in parallel.

microbiology↗