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bioRxiv2020

Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations

Statistical and epidemiological data imply temperature sensitivity of the SARS-CoV-2 coronavirus. However, the molecular level understanding of the virus structure at different temperature is still not clear. Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the solvent exposed domain of Spike protein, namely S1, is more mobile than the transmembrane domain, S2. Structural studies implied the presence of several charged residues on the surface of N-terminal Domain of S1 which are optimally oriented at 10-30 {degrees}C. Bioinformatics analyses indicated that it is capable of binding to other human receptors and should not be disregarded. Additionally, we found that receptor binding motif (RBM), present on the receptor binding domain (RBD) of S1, begins to close around temperature of 40 {degrees}C and attains a completely closed conformation at 50 {degrees}C. The closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues. Our results clearly show that there are active and inactive states of the protein at different temperatures. This would not only prove beneficial for understanding the fundamental nature of the virus, but would be also useful in the development of vaccines and therapeutics. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/145086v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1e631eeorg.highwire.dtl.DTLVardef@1d83278org.highwire.dtl.DTLVardef@d98d3borg.highwire.dtl.DTLVardef@c75b7f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIStatistical and epidemiological evidence show that external climatic conditions influence the SARS-CoV infectivity, but we still lack a molecular level understanding of the same. C_LIO_LIHere, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2. C_LIO_LIResults show that the Spikes S1 domain is very sensitive to external atmospheric conditions compared to the S2 transmembrane domain. C_LIO_LIThe N-terminal domain comprises of several solvent exposed charged residues that are capable of binding to human proteins. The region is specifically stable at temperatures ranging around 10-30{degrees} C. C_LIO_LIThe Receptor Binding Motif adopts a closed conformation at 40{degrees}C and completely closes at higher temperatures making it unsuitable of binding to human receptors C_LI

biophysics↗

bioRxiv2020

Characterization of the evolutionary dynamics of influenza A H3N2 hemagglutinin

Virus evolution drives the annual influenza epidemics in human population worldwide. However, it has been challenging to evaluate the mutation effect of the influenza virus on evading the population immunity. In this study, we introduce a novel statistical and computational approach to measure the dynamic molecular determinants underlying epidemics by the effective mutations (EMs), and account for the time of waning mutation advantage against herd immunity by the effective mutation periods (EMPs). Extensive analysis is performed on the genome and epidemiology data of 13-year worldwide H3N2 epidemics involving nine regions in four continents. We showed that the identified EM processed similar profile in geographically adjacent regions, while only 40% are common to Europe, North America, Asia and Oceania, indicating that the regional specific mutations also contributed significantly to the global H3N2 epidemics. The mutation dynamics calibrated that around 90% of the common EMs underlying global epidemics were originated from South East Asia, led by Thailand and India, and the rest were originated from North America. New Zealand was found to be the dominate sink region of H3N2 circulation, followed by UK. All regions might act as the intersection in the H3N2 transmission network. The proposed methodology provided a way to characterize key amino acids from the genetic epidemiology point of view. This approach is not restricted by the genomic region or type of the virus, and will find broad applications in identifying therapeutic targets for combating infectious diseases.

evolutionary biology↗

bioRxiv2020

What happens after a blood meal? A transcriptome response from the main tissues involved in egg production in Rhodnius prolixus, an insect vector of Chagas disease

The blood-sucking hemipteran Rhodnius prolixus is a vector of Chagas disease, one of the most neglected tropical diseases affecting several million people, mostly in Latin America. The blood meal is an event with a high epidemiological impact since in adult mated females it initiates the production of hundreds of eggs. By means of RNA-Sequencing (RNA-Seq) we have examined how a blood meal influences mRNA expression in the central nervous system (CNS), fat body and ovaries in order to promote egg production, focusing on tissue-specific responses under controlled nutritional conditions. We illustrate the cross talk between reproduction and a) lipids, proteins and trehalose metabolism, b) neuropeptide and neurohormonal signaling, and c) the immune system. Overall, our molecular evaluation confirms and supports previous studies and provides an invaluable molecular resource for future investigations on different tissues involved in successful reproductive events. Analyses like this can be used to increase the chances of developing novel strategies of vector population control by translational research, with less impact on the environment and more specificity for a particular organism.Author summary The blood-sucking hemipteran Rhodnius prolixus is one of the main vectors of Chagas disease. The blood meal is an event with a high epidemiological impact since in adult mated females, blood-gorging leads to the production of hundreds of eggs. This work describes an in-depth central nervous system (CNS), ovary and fat body transcriptome analysis, focusing on transcripts related to blood intake which may be relevant in promoting egg production. To date, the principle focus in Chagas disease prevention is on the elimination of triatomine vectors and their progeny. This work will serve as a starting point for initiating novel investigations on targets identified with a potential for use in vector control; for example using specific genes to generated symbiont-mediated RNAi, a powerful technology which provides a novel means in biocontrol against tropical disease vectors.View Full Text

molecular biology↗

bioRxiv2020

Accounting for imperfect detection reveals role of host traits in structuring viral diversity of a wild bat community

Understanding how multi-scale host heterogeneity affects viral community assembly can illuminate ecological drivers of infection and host-switching. Yet, such studies are hindered by imperfect viral detection. To address this issue, we used a community occupancy model – refashioned for the hierarchical nature of molecular-detection methods – to account for failed detection when examining how individual-level host traits affect herpesvirus richness in eight species of wild bats. We then used model predictions to examine the role of host sex and species identity on viral diversity at the levels of host individual, population, and community. Results demonstrate that cPCR and viral sequencing failed to perfectly detect viral presence. Nevertheless, model estimates correcting for imperfect detection show that reproductively active bats, especially reproductively active females, have significantly higher viral richness, and host sex and species identity interact to affect viral richness. Further, host sex significantly affects viral turnover across host populations, as females host more heterogeneous viral communities than do males. Results suggest models of viral ecology benefit from integration of multi-scale host factors, with implications for bat conservation and epidemiology. Furthermore, by accounting for imperfect detection in laboratory assays, we demonstrate how statistical models developed for other purposes hold promising possibilities for molecular and epidemiological applications.Competing Interest StatementThe authors have declared no competing interest.View Full Text

ecology↗

bioRxiv2020

How do sex biases in demography and disease characteristics affect the spread of sexually transmitted infections?

The epidemiology of sexually transmitted infections (STIs) is inherently linked to host mating dynamics. Studies across many taxa show that adult sex ratio, a major determinant of host mating dynamics, is often skewed - sometimes strongly - toward males or females. However, few predictions exist for the effects of skewed sex ratio on STI epidemiology, and none when coupled with sex biased disease characteristics. Here we use mathematical modelling to examine how interactions between sex ratio and disease characteristics affect STI prevalence in males and females. Notably, we find that while overall disease prevalence peaks at equal sex ratios, prevalence per sex peaks at skewed sex ratios. Furthermore, disease characteristics, sex-biased or not, drive predictable differences in male and female STI prevalence as sex ratio varies, with higher transmission and lower virulence generally increasing differences between the sexes for a given sex ratio. These findings may be due to a balance between increased per-capita mating in the less common sex, and a reduction in mating rate - hence disease prevalence - at the population level. Our work reveals new insights into how STI prevalence in males and females depends on a complex interaction between host population sex ratio and disease characteristics.

animal behavior and cognition↗

bioRxiv2020

A global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at Pathogenwatch

BackgroundMicrobial whole-genome sequencing (WGS) is now increasingly used to inform public health investigations of infectious disease. This approach has transformed our understanding of the global population structure of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever. WGS has been particularly informative for understanding the global spread of multi-drug resistant (MDR) typhoid. As WGS capacity becomes more decentralised, there is a growing opportunity for collaboration and sharing of surveillance data within and between countries to inform disease control policies. This requires freely available, community driven tools that reduce the barriers to access genomic data for public health surveillance and that deliver genomic data on a global scale. MethodsHere we present the Pathogenwatch (https://pathogen.watch/styphi) scheme for S. Typhi, a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data to identify high-risk clones at a population level. Data are delivered in single genome reports or in collections of genomes combined with geographic and other data using trees, maps and tables. ResultsWe show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are largely concordant with phenotypic drug susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from over 4,300 public genomes available in the application. ConclusionsPathogenwatch democratises genomic epidemiology of S. Typhi by providing an intuitive entry point for the analysis of WGS and linked epidemiological data, enabling international public health monitoring of the emergence and spread of high risk clones.

genomics↗

bioRxiv2020

Novel algorithms for PFGE bacterial typing: Number of co-migrated DNA fragments, linking PFGE to WGS results and computer simulations for evaluation of PulseNet international typing protocols

BackgroundStandard protocols for Pulsed-field gel electrophoresis (PFGE) were adopted and being used in a global scale for surveillance of many bacterial food-borne diseases. Matched PFGE bands are considered regardless of co-migration of different DNA fragments. Molecular epidemiology is turning toward whole genome sequencing (WGS). Although, WGS results can be digested In-silico, PFGE and WGS data are being compared separately. We describe a new image analysis algorithm that enables identification of how many DNA fragments co-migrate during PFGE. We built a database that compare described PFGE results to in-silico obtained digestion models (from WGS). Reliability of the method was assessed in-silico using novel computer simulation approach. From WGS, 1,816 digestion model (DMs) were obtained as recommended by PulseNet international. Simulation codes were designed to predict PFGE profiles when DMs are separated at 5% PFGE resolution in addition to expected co-migration levels. ResultsPFGE simulation has shown that about 35% of DNA fragments co-migrate at 5% PFGE resolution. Similar result was obtained when wet-lab PFGE profiles were analyzed using image analysis algorithm mentioned earlier. When image analysis results were compared to DMs, results returned by geltowgs.uofk.edu database revealed reasonable relatedness to DMs. In terms of number of PFGE typable DNA fragments, 45,517 were typable (representing 46.54% out of 97,801). Previously mentioned typable fragments (in terms of typable sizes) comprised 91.24% of the sum of nucleotides of all chromosomes tested (7.24 billion bp). However, significant variations were shown within and between different digestion protocols. ConclusionsIdentification of co-migration levels will reveal the third dimension of PFGE profiles. This will provide a better way for evaluating isolate relationships. Linking old PFGE results to WGS by means of simulation demonstrated here will provide a chance to link millions of PFGE epidemiological data accumulated during the last 24 years to the new WGS era. Evaluation of population dynamics of pathogenic bacteria will be deeper through space and time. Selection of restriction enzymes for PFGE typing will have a powerful in-silico evaluation tool.

microbiology↗

bioRxiv2020

Haplotype Explorer: an infection cluster visualization tool for spatiotemporal dissection of the COVID-19 pandemic

The worldwide eruption of COVID-19 that began in Wuhan, China in late 2019 reached 10 million cases by late June 2020. In order to understand the epidemiological landscape of the COVID-19 pandemic, many studies have attempted to elucidate phylogenetic relationships between collected viral genome sequences using haplotype networks. However, currently available applications for network visualization are not suited to understand the COVID-19 epidemic spatiotemporally, due to functional limitations That motivated us to develop Haplotype Explorer, an intuitive tool for visualizing and exploring haplotype networks. Haplotype Explorer enables people to dissect epidemiological consequences via interactive node filters to provide spatiotemporal perspectives on multimodal spectra of infectious diseases, including introduction, outbreak, expansion, and containment, for given regions and time spans. Here, we demonstrate the effectiveness of Haplotype Explorer by showing an example of its visualization and features. The demo using SARS-CoV-2 genome sequences is available at https://github.com/TKSjp/HaplotypeExplorer SummaryA lot of software for network visualization are available, but existing software have not been optimized to infection cluster visualization against the current worldwide invasion of COVID-19 started since 2019. To reach the spatiotemporal understanding of its epidemics, we developed Haplotype Explorer. It is superior to other applications in the point of generating HTML distribution files with metadata searches which interactively reflects GISAID IDs, locations, and collection dates. Here, we introduce the features and products of Haplotype Explorer, demonstrating the time-dependent snapshots of haplotype networks inferred from total of 4,282 SARS-CoV-2 genomes.

genomics↗

bioRxiv2020

Ancestry Influences on the Molecular Presentation of Tumours

Epidemiological studies have identified innumerable ways in which cancer presentation and behaviour is associated with patient ancestry. The molecular bases for these relationships remain largely unknown. We analyzed ancestry associations in the somatic mutational landscape of 12,774 tumours across 33 tumour-types, including 2,562 with whole-genome sequencing. Ancestry influences both the number of mutations in a tumour and the evolutionary timing of when they occur. Specific mutational signatures are associated with ancestry, reflecting potential differences in exogenous and endogenous oncogenic processes. A subset of known cancer driver genes was mutated in ancestry-associated patterns, with transcriptomic consequences. Cancer genome sequencing data is not well-balanced in epidemiologic factors; these data suggest ancestry strongly shapes the somatic mutational landscape of cancer, with potential functional implications.

cancer biology↗

bioRxiv2020

A computational model of homeostatic cerebellarcompensation of ageing in vestibulo-ocular reflex adaptation

The vestibulo-ocular reflex (VOR) stabilizes vision during head motion. Age-related changes of vestibular neuroanatomical properties predict a linear decay of VOR function. Nonetheless, human epidemiological data show a stable VOR function across the life span. In this study, we model cerebellum-dependent VOR adaptation to relate structural and functional changes throughout aging. We consider three neurosynaptic factors that may codetermine VOR adaptation during aging: the electrical coupling of inferior olive neurons, the intrinsic plasticity of Purkinje cell (PC) synapses, and long-term spike timing-dependent plasticity at parallel fiber - PC synapses and mossy fiber - medial vestibular nuclei synapses. Our cross-sectional aging analyses suggest that long-term plasticity acts as a global homeostatic mechanism that underpins the stable temporal profile of VOR function. The results also suggest that the intrinsic plasticity of PC synapses operates as a local homeostatic mechanism that further sustains the VOR at older ages. Importantly, the computational epidemiology approach presented in this study allows discrepancies among human cross-sectional studies to be understood in terms of interindividual variability in older individuals. Finally, our longitudinal aging simulations show that the amount of residual fibers coding for the peak and trough of the VOR cycle constitutes a predictive hallmark of VOR trajectories over a lifetime.

neuroscience↗

bioRxiv2020

Transmission and genetic adaptation of Achromobacter in cystic fibrosis

Achromobacter species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen is associated with antibiotic resistance and more severe disease outcomes. Nonetheless, little is known about the extent of transmission and antibiotic resistance development in Achromobacter infections. We sequenced the genomes of 101 clinical isolates of Achromobacter (A. xylosoxidans based on MALDI-TOF/API N20 typing) collected from 51 patients with CF--the largest longitudinal dataset to-date. We performed phylogenetic analysis on the genomes and combined this with epidemiological and antibiotic resistance data to identify patient-to-patient transmission and development of antibiotic resistance. We found that MALDI-TOF/API N20 was not sufficient for Achromobacter species-level typing, and that the population of Achromobacter isolates was composed of five different species where A. xylosoxidans accounted for 52% of infections. Most patients were infected by unique Achromobacter clone types; nonetheless, suspected patient-to-patient transmission cases identified by shared clone types were observed in 35% (N=18) of patients. In 15 of 16 cases the suspected transmissions were further supported by genome- or clinic visit-based epidemiological analysis. Finally, we found that resistance developed over time. We show that whole-genome sequencing (WGS) is essential for Achromobacter species typing and patient-to-patient transmission identification which was identified in A. ruhlandii, A. xylosoxidans and, for the first time, A. insuavis. Furthermore, we show that the development of antibiotic resistance is associated with chronic Achromobacter infections. Our findings emphasize that transmission and antibiotic resistance should be considered in future treatment strategies.

genomics↗

bioRxiv2020

When does parasitism maintain sex in the absence of Red Queen Dynamics?

AO_SCPLOWBSTRACTC_SCPLOWParasites can select for sexual reproduction in host populations, preventing replacement by faster growing asexual lineages. This is usually attributed to so-called "Red Queen Dynamics" (RQD), where antagonistic coevolution causes fluctuating selection in allele frequencies, which provides sex with an advantage over asex. However, parasitism may also maintain sex in the absence of RQD when sexual populations are more genetically diverse - and hence more resistant, on average - than clonal populations, allowing sex and asex to stably coexist. While the maintenance of sex due to RQD has been studied extensively, the conditions that allow sex and asex to stably coexist have yet to be explored in detail. In particular, we lack an understanding of how host demography and parasite epidemiology affect the maintenance of sex in the absence of RQD. Here, I use an eco-evolutionary model to show that both population density and the type and strength of virulence are important for maintaining sex, which can be understood in terms of their effects on disease prevalence and severity. In addition, I show that even in the absence of heterozygote advantage, asexual heterozygosity affects coexistence with sex due to variation in niche overlap. These results reveal which host and parasite characteristics are most important for the maintenance of sex in the absence of RQD, and provide empirically testable predictions for how demography and epidemiology mediate competition between sex and asex.

evolutionary biology↗

bioRxiv2020

Experimental parasite community perturbation reveals associations between Sin Nombre virus and gastrointestinal nematodes in a rodent reservoir host

Individuals are often co-infected with several parasite species, yet measuring within-host interactions remains difficult in the wild. Consequently, such interactions impacts on host fitness and epidemiology are often unknown. We used anthelmintic drugs to experimentally reduce nematode infection and measured the effects on both nematodes and the important zoonosis Sin Nombre virus (SNV) in its primary wild reservoir (Peromyscus spp.). Treatment significantly reduced nematode infection, but increased SNV seroprevalence. Furthermore, mice that were co-infected with both nematodes and SNV were in better condition and survived as much as four times longer than mice infected with either parasite alone. These results highlight the importance of investigating multiple parasites for understanding interindividual variation and epidemiological dynamics in reservoir populations with zoonotic transmission potential.

ecology↗

bioRxiv2020

Population Genomics of Plasmodium vivax in Panama to Assess the Risk of Case Importation on Malaria Elimination

Malaria incidence in Panama has plateaued in recent years in spite of elimination efforts, with almost all cases caused by Plasmodium vivax. Notwithstanding, overall malaria prevalence remains low (fewer than 1 case per 1000 persons). We used selective whole genome amplification to sequence 96 P. vivax samples from Panama collected between 2007 and 2019 to study the population structure and transmission dynamics of the parasite. Imported cases resulting from increased levels of human migration could threaten malaria elimination prospects, and four of the samples evaluated came from individuals with travel history. We explored patterns of recent common ancestry among the samples and observed that a single highly genetically related lineage was dominant among the samples (47 out of 59 samples with good sequencing coverage), spanning the entire period of the collection (2007-2019) and all regions of the country. We also found a second, smaller clonal lineage of four parasites collected between 2017 and 2019. To explore the regional context of Panamanian P. vivax we conducted principal components analysis and constructed a neighbor-joining tree using these samples and samples collected worldwide from a previous study. Three of the four samples with travel history clustered with samples collected from their suspected country of origin (consistent with importation), while one appears to have been a result of local transmission. The small number of genetically unique Panamanian P. vivax samples clustered with samples collected from Colombia, suggesting they represent the genetically similar ancestral P. vivax population in Panama or were recently imported from Colombia. The low diversity we observe in Panama indicates that this parasite population has been previously subject to a severe bottleneck and may be eligible for elimination. Additionally, while we confirmed that P. vivax is imported to Panama from diverse geographic locations, the lack of impact from imported cases on the overall parasite population genomic profile suggests that onward transmission from such cases is limited and that imported cases may not presently pose a major barrier to elimination. Author SummaryPanama has greatly reduced P. vivax incidence, however, this progress has plateaued. Understanding parasite transmission patterns and identifying imported cases is critical to help Panama and other countries succeed in their elimination efforts. Genomic epidemiology and population genomics can help provide information needed to inform malaria control policy. In this study, we collected 100 Panamanian P. vivax samples from two collection periods (2007-2009 and 2017-2019), of which 59 yielded usable sequencing data. 4 samples had patient travel history data associated with them. We found that the majority of samples belong to a single highly related lineage, termed CL1. This lineage has persisted since at least 2007. We also highlight how genomic epidemiology can be used to spotlight parasites that may be imported as a result of human migration, as well as corroborate or refute the country of origin as suggested by patient travel history. We observe no evidence of outcrossing between these potentially imported parasites and the local Panamanian parasite population, suggesting that imported parasites are not driving ongoing malaria transmission in Panama. The low diversity we observe in Panama indicates that this parasite population has been previously subject to a severe bottleneck and may be eligible for elimination.

microbiology↗

bioRxiv2020

SARS-CoV-2 lineage B.6 is the major contributor to transmission in Malaysia

BackgroundAs of June 30, 2020, Malaysia had confirmed 8,639 cases of COVID-19. About 39% of these were associated with a religious mass gathering event held in Kuala Lumpur between February 27 and March 1, 2020, which drove community transmission during Malaysias main wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to understand the molecular epidemiology. MethodsWe obtained whole genome sequences of SARS-CoV-2 from 58 COVID-19 patients in Kuala Lumpur, Malaysia, and performed phylogenetic analyses on these and a further 50 Malaysian sequences available in the GISAID database. Malaysian lineage B.6 sequences were further analysed with all available worldwide lineage B.6 sequences. ResultsNine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the mass gathering and became predominant (63%) despite being relatively rare (1.4%) among available global sequences. Increases in reported cases and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly associated with travel and showed limited onward transmission. There were also temporally-correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. We also report the presence of a nsp3-C6310A substitution found in 40.5% of global B.6 sequences which has associated with reduced sensitivity in a commercial assay. ConclusionLineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the region. Author SummaryThe COVID-19 pandemic in Malaysia was driven mainly by transmission following a religious mass gathering held in Kuala Lumpur at the end of February. To study the genetic epidemiology of SARS-CoV-2 in Malaysia, we analysed 50 available and 58 newly-generated Malaysian whole genome virus sequences. We found that lineage B.6, rare (1.4%) globally, first appeared after the mass gathering and became the most predominant (62.9%) in Malaysia. Increases in COVID-19 cases and locally-acquired B.6 strains were temporally linked. Non-B.6 viruses were mainly associated with travel and showed limited spread. Increases in B.6 viruses in Southeast Asian countries, India and Australia were linked to participants returning from this mass gathering. Altogether, 95.3% of global B.6 sequences originated in Asia or Australia. We also report a mutation in the virus nsP3 gene found in 40.5% of global B.6 sequences and associated with reduced detection by a commercial diagnostic test. In conclusion, the religious mass gathering in Kuala Lumpur was associated with the main wave of COVID-19 cases of predominantly B.6 lineage in Malaysia, and subsequent spread of B.6 viruses regionally. Genome sequence data provides valuable insight into virus spread and is important for monitoring continued accuracy of diagnostic kits.

microbiology↗

bioRxiv2020

Dengue Disease Dynamics are Modulated by the Combined Influence of Precipitation and Landscapes: A Machine Learning-based Approach

BackgroundDengue is an endemic vector-borne disease influenced by environmental factors such as landscape and climate. Previous studies separately assessed the effects of landscape and climate factors on mosquito occurrence and dengue incidence. However, both factors interact in time and space to affect mosquito development and dengue disease transmission. For example, eggs laid in a suitable environment can hatch after being submerged in rain or flood water. ObjectivesThis study aimed to investigate the combined influences of landscape and climate factors on mosquito occurrence and dengue incidence. MethodsEntomological, epidemiological, and landscape data from the rainy season (July-December) were obtained from respective government agencies in Metro Manila, Philippines, from 2012 to 2014. Temperature, precipitation, and vegetation data were obtained through remote sensing. A random forest algorithm was used to select the landscape and climate variables. Afterwards, using the identified key variables, a model-based (MOB) recursive partitioning was implemented to test the combinatory influences of landscape and climate factors on the ovitrap index and dengue incidence. ResultsThe MOB recursive partitioning for the ovitrap index indicated that mosquito occurrence was higher in high residential density areas, where industrial areas also exist and are well connected with roads. Precipitation was another key covariate modulating the effects of landscape factors, possibly by expanding breeding sites and activating mosquito reproduction. Moreover, the MOB recursive partitioning indicated that precipitation was the main predictor of dengue incidence, with a stronger effect in high residential density and commercial areas. DiscussionPrecipitation with floods has epidemiologically important implications by damaging shelters and causing population displacement, thus increasing exposure to dengue vectors. Our findings suggest that the intensification of vector control during the rainy season can be prioritized in residential and commercial areas to better control dengue disease dynamics.

ecology↗

bioRxiv2020

Virome-wide serological profiling reveals association of herpesviruses with obesity

The relationship between viral infection and obesity has been known for several decades but epidemiological data related to obesity is limited to only a few viral pathogens. To identify associations between viral infections and obesity, a high-throughput virome-wide serological profiling tool, VirScan, was used to measure antibody responses to a wide range of viruses. Serum specimens from 457 Qatari adults (lean=184;obese=273) and 231 Qatari children (lean=111;obese=120) were assessed by VirScan. Pediatric specimens were simultaneously tested by conventional serology for several herpesviruses to validate VirScan results. Viral association with obesity was determined by calculation of odds ratio (OR) and p-values from Fisher test, and by multivariate regression analysis to adjust for age and gender, with Bonferroni correction for multiple testing. Comprehensive serological profiling of Qatari adult population with VirScan revealed positive and negative associations (p<0.05) of antibody responses to members of Herpesviridae and Picornaviridae families, respectively, with obesity. After adjusting p-values for multiple comparisons, only herpes simplex virus 1 (HSV-1) and Rhinovirus A were positively (OR=3.3; 95%CI 2.15-4.99; p=2.787E-08) and negatively (OR=0.4; 95%CI 0.26-0.65; p=1.175E-03) associated with obesity. At the peptide level, higher prevalence of antibodies against several peptide epitopes of HSV-1/2 was positively (OR=2.35-3.82; p[≤]3.981E-05) associated with obesity. No such associations were seen at the species or peptide levels in the pediatric population. By multivariate regression analysis, HSV-1 was independently associated with obesity irrespective of age and gender. These findings are in agreement with limited data on the adipogenic properties of HSV-1 observed in vitro. ImportanceThe state of Qatar has one of the highest rates of obesity and associated morbidities in the world. Although obesity is predominantly caused by the intake of high calorie diet and reduced physical activities, other factors including infections with certain viruses have been reported. Among these viruses, human adenoviruses were widely studied but epidemiological data for other viruses in relation to human obesity are limited. Here, we studied the association of obesity in Qatari adults and children with a wide range of viral pathogens using VirScan, a virome-wide serological profiling tool. Our results indicate significant association HSV-1 with obesity in the adult population only. Furthermore, we have identified a set of HSV peptides as candidate obesogenic factors for future studies.

microbiology↗

bioRxiv2020

A highly rifampicin resistant Mycobacterium tuberculosis strain emerging in Southern Brazil

Here we described phenotypical, molecular and epidemiological features of a highly rifampicin-resistant Mycobacterium tuberculosis strain emerging in Southern Brazil, that carries an uncommon insertion of 12 nucleotides at the codon 435 in the rpoB gene. Employing a whole-genome sequencing-based study on drug-resistant Mycobacterium tuberculosis strains, we identified this emergent strain in 16 (9.19%) from 174 rifampicin-resistant clinical strains included. Nine of these 16 strains were available to minimum inhibitory concentration determination and for all of them was found a high rifampicin-resistance level ([≥] to 32 mg/L). This high resistance level could be explained by structural changes into the RIF binding site of RNA polymerase caused by the insertions, and consequent low-affinity interaction with rifampicin complex confirmed through protein modeling and molecular docking simulations. Epidemiological investigation showed that most of the individuals (56.25%) infected by the studied strains were prison inmate individuals or that spent some time in prison. The phylogenomic approach revealed that all strains carrying on the 12 nucleotide insertion belonged to the same genomic cluster, evidencing a communal transmission chain involving inmate individuals and community. We stress the importance of tuberculosis genomic surveillance and the introduction of measures to interrupt the Mycobacterium tuberculosis transmission chain in this region.

genomics↗