Zoonotic pathogens, those transmitted from animals to humans, constitute a major public health risk with high associated global economic costs. Diseases associated with these pathogens represent more than 60% of emerging infectious diseases and predominantly originate in wildlife (1). Over the last decades, the emergence and re-emergence of zoonotic pathogens have led to an increasing number of epidemics, as illustrated by the current Covid-19 pandemic. There is ample evidence that human impact on native ecosystems such as deforestation, agricultural development, and urbanization, is linked to spillover of pathogens from animals to humans (2). However, research and calls to action have mainly focused on the importance of surveillance and prevention of zoonotic emergences along landscape interfaces, with special emphasis on tropical forests and agroecosystems, and studies and reviews pointing out the zoonotic risk associated with cities are scarce.  Additionally, cities are sometimes wrongly seen as one homogeneous ecosystem, almost exclusively human, with a Northern hemisphere-biased perception of what a city is, which fails to take into account the ecological and socio-economic diversities that can constitute an urban area.

Here, Dobigny and Morand (3) aim to draw attention to the importance of urban ecosystems in zoonotic risk and advocate that further attention should be paid to urban, peri-urban and suburban areas. In this well-organized and well-documented review, the authors show, using updated literature, that cities are places where massive contacts occur between wildlife, domestic animals, and human inhabitants (thus constituting spillover opportunities), and that it is even likely that human and wildlife contact in urban centers is more prevalent than in wild areas, perhaps contrary to intuition. Indeed, cities currently constitute the most important environment of human life and are places for millions of close interactions between humans and animals, including pets and domestic animals, wild animals through the intrusion of wild urban-adapted species (e.g., some bat, rodent, or bird species among others), manipulation and consumption of wildlife meat, and the existence of wildlife meat markets, which all constitute a major risk for zoonotic spillover. In cities, lab escapees of zoonotic pathogens also exist, and trends of adaptation to urban ecological conditions of many vectors of primary health importance is also a concern. The authors further argue that cities are predominant places for both epidemic amplification of human-human transmitted pathogens, because they are places with high human densities and population growth, and for dissemination of reservoirs, vectors and pathogens, as they are transport hubs. Dobigny & Morand further predict, likely correctly, that cities may be important places for pathogen evolution.  Finally, they propose actions and recommendations to limit the risk of zoonotic spillover events from urban ecosystems and future directions for research aiming at assessing this risk. 

The reviewers found the manuscript well-organized and presented, timely, and bringing novel contributions to the field of zoonotic emergence. I strongly recommend this article, which should benefit a large audience, particularly in the context of the current Covid-19 pandemics and the ongoing One Health initiatives aiming at preventing future zoonotic disease emergence (4). 

References

(1) Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman JL, Daszak P (2008) Global trends in emerging infectious diseases. Nature, 451, 990–993. https://doi.org/10.1038/nature06536

(2) White RJ, Razgour O (2020) Emerging zoonotic diseases originating in mammals: a systematic review of effects of anthropogenic land-use change. Mammal Review, 50, 336–352. https://doi.org/10.1111/mam.12201

(3) Dobigny G, Morand S (2022) Zoonotic emergence at the animal-environment-human interface: the forgotten urban socio-ecosystems. Zenodo, 6444776, ver. 3 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.5281/zenodo.6444776

(4) Morand S, Lajaunie C (2021) Biodiversity and COVID-19: A report and a long road ahead to avoid another pandemic. One Earth, 4, 920–923. https://doi.org/10.1016/j.oneear.2021.06.007

The impact of virus infection of a plant on an aphid’s behaviour has been observed in many studies [1]. Indeed, virus infection can alter plant biochemistry through the emission of volatile organic compounds and plant tissue content modification. These alterations can further impact the interactions between plants and aphids. However, although it is a well-known phenomenon, very few studies have explored the consequences of plant virus infection on the gene expression of aphids to understand better the aphid’s manipulation by the plant virus. In this context, the recommended study [2] reports a comprehensive transcriptomic analysis of the genes expressed by one aphid species, Myzus persicae, a vector of several plant viruses, when feeding on plants. Michelle Heck underlined how significant this study is for comprehending the molecular bases of aphid-vector manipulation by plant viruses (see below).

Interestingly, the study design has integrated several factors that might influence the gene expression of M. persicae when feeding on the plant. Indeed, the authors investigated the effect of two plant species (Arabidopsis thaliana and Camelia sativa) and two virus species [turnip yellows virus (TuYV) and cauliflower mosaic virus (CaMV)]. Noteworthy, the transmission mode of TuYV is circulative and persistent, while CaMV is transmitted by a semi-persistent non-circulative mode. As Juan José Lopez Moya mentioned, multiple comparisons allowed the identification of the different responses of aphids in front of different host plants infected or not by different viruses (see below). This publication is complementary to a previous publication from the same team focusing on plant transcriptome analysis [3].

Thanks to their experimental design, the authors identified genes commonly deregulated by both viruses and/or both plant species and deregulated genes by a single virus or a single plant. Figure 4 nicely summarizes the number of deregulated genes. A thorough discussion on the putative role of deregulated genes in different conditions gave a comprehensive follow-up of the results and their impact on the current knowledge of plant-virus-vector interactions.

This study has now opened the gate to promising research focusing on the functional validation of the identified genes while also narrowing the study from the body to the tissue level.

References:

1. Carr JP, Tungadi T, Donnelly R, Bravo-Cazar A, Rhee S-J, Watt LG, Mutuku JM, Wamonje FO, Murphy AM, Arinaitwe W, Pate AE, Cunniffe NJ, Gilligan CA (2020) Modelling and manipulation of aphid-mediated spread of non-persistently transmitted viruses. Virus Research, 277, 197845. https://doi.org/10.1016/j.virusres.2019.197845

2. Chesnais Q, Golyaev V, Velt A, Rustenholz C, Verdier M, Brault V, Pooggin MM, Drucker M (2022) Transcriptome responses of the aphid vector Myzus persicae are shaped by identities of the host plant and the virus. bioRxiv , 2022.07.18.500449, ver. 5 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2022.07.18.500449

3. Chesnais Q, Golyaev V, Velt A, Rustenholz C, Brault V, Pooggin MM, Drucker M (2022) Comparative Plant Transcriptome Profiling of Arabidopsis thaliana Col-0 and Camelina sativa var. Celine Infested with Myzus persicae Aphids Acquiring Circulative and Noncirculative Viruses Reveals Virus- and Plant-Specific Alterations Relevant to Aphid Feeding Behavior and Transmission. Microbiology Spectrum, 10, e00136-22. https://doi.org/10.1128/spectrum.00136-22

Structural variations (SVs) play a key role in viral evolution, and therefore they are also important for infection dynamics. However, the contribution of structural variations to the evolution of double-stranded viruses is limited. This knowledge can help to understand the population dynamics and might be crucial for the future development of viral attenuated vaccines.

In this study, Fuandila et al (1) use the Cyprinid herpesvirus 3 (CyHV-3), commonly known as koi herpesvirus (KHV), to investigate the variability and contribution of structural variations (SV) for viral evolution after 99 passages in vitro. This virus, with the largest genome among herperviruses, causes a lethal infection in common carp and koi associated with mortalities up to 95% (2). Interestingly, KHV infections are caused by haplotype mixtures, which possibly are a source of genome diversification, but make genomic comparisons more difficult.

The authors have used ultra-deep long-read sequencing of two passages, P78 and P99, which were previously described to have differences in virulence. They have found a surprisingly high and wide distribution of SVs along the genome, which were enriched in inversion and deletion events and that often led to defective viral genomes. Although it is known that these defective viral genomes negatively impact viral replication, their implications for virus persistence are still unclear.

Subsequently, the authors concentrated on the virulence-relevant region ORF150, which was found to be different in P78 (deletion in 100% of the reads) and P99 (reference-like haplotype). To understand this loss and gain of full ORF150, they searched for SV turn-over in 10 intermediate passages. This analysis revealed that by passage 10 deleted and inverted (attenuated) haplotypes had already appeared, steadily increased frequency until P78, and then completely disappeared between P78 and P99. This is a striking result that raises new questions as to how this clearance occurs, which is really important as these reversions may result in undesirable increases in virulence of live-attenuated vaccines.

We recommend this preprint because its use of ultra-deep long-read sequencing has permitted to better understand the role of SV diversity and dynamics in viral evolution. This study shows an unexpectedly high number of structural variations, revealing a novel source of virus diversification and confirming the different mixtures of haplotypes in different passages, including the gain of function. This research provides basic knowledge for the future design of live-attenuated vaccines, to prevent the reversion to virulent viruses. 

References

(1)  Fuandila NN, Gosselin-Grenet A-S, Tilak M-K, Bergmann SM, Escoubas J-M, Klafack S, Lusiastuti AM, Yuhana M, Fiston-Lavier A-S, Avarre J-C, Cherif E (2022) Structural variation turnovers and defective genomes: key drivers for the in vitro evolution of the large double-stranded DNA koi herpesvirus (KHV). bioRxiv, 2022.03.10.483410, ver. 4 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2022.03.10.483410

(2)  Sunarto A, McColl KA, Crane MStJ, Sumiati T, Hyatt AD, Barnes AC, Walker PJ. Isolation and characterization of koi herpesvirus (KHV) from Indonesia: identification of a new genetic lineage. Journal of Fish Diseases, 34, 87-101. https://doi.org/10.1111/j.1365-2761.2010.01216.x 

Various species of Ebolavirus have caused, and are still causing, zoonotic outbreaks and public health crises in Africa. Bats have long been hypothesized to be important reservoir populations for a series of viruses such as Hendra or Marburg viruses, the severe acute respiratory syndrome coronavirus (SARS-CoV, SARS-CoV-2) as well as Ebolaviruses [2, 3]. However the ecology of disease dynamics, disease transmission, and coevolution with their natural hosts of these viruses is still poorly understood, despite their importance for predicting novel outbreaks in human or livestock populations. The evidence that bats function as sylvatic reservoirs for Ebola viruses is yet only partial. Indeed, only few serological studies demonstrated the presence of Ebolavirus antibodies in young bats [4], albeit without providing positive controls of viral detection or identifying the viral species (via PCR). There is thus an unexplained discrepancy between serological data and viral detection [2, 4]. 

In this article, Pleydell et al. [1] use a modeling approach as well as published serological and age-structure (of the bat population) data to calibrate the model simulations. The study starts with the development of an age-structured epidemiological model which includes seasonal birth pulses and waning immunity, both generating pulses of Ebolavirus transmission within a colony of African straw-coloured fruit bats (Eidolon helvum). The epidemiological dynamics of such system of ordinary differential equations can generate annual outbreaks, skipped years or multi-annual cycles up to chaotic dynamics. Therefore, the calibration of the parameters, and the definition of biologically relevant priors, are key. To this aim, the serological data are obtained from a previous study in Cameroon [5], and the age structured of the bat population (birth and mortality) from a population study in Ghana [6]. These data are integrated into the Bayesian analysis and statistical framework to fit the model and generate predictions. In a nutshell, the authors show an overlap between the data and credibility intervals generated by the calibrated model, which thus explains well the seasonality of age-structure, namely changes in pup presence, number of lactating females, or proportion of juveniles in May. The authors can estimate that 76% of adults and 39% of young bats do survive each year, and infections are expected to last one and a half weeks. The epidemiological model predicts that annual birth pulses likely generate annual disease outbreaks, so that weeks 30 to 31 of each year, are predicted to be the best period to isolate the circulating Ebolavirus in this bat population. From the model predictions, the authors estimate the probability to have missed an infectious bat among all the samples tested by PCR being approximately of one per two thousands. The disease dynamics pattern observed in the serology data, and replicated by the model, is likely driven by seasonal pulses of young susceptible bats entering the population. This seasonal birth event increases the viral transmission, resulting in the observed peak of viral prevalence. With the inclusion of immunity waning and antibody persistence, the model results illuminate therefore why previous studies have detected only few positive cases by PCR tests, in contrast to the evidence from serological data. 

 This study provides a first proof of principle that epidemiological modeling, despite its many simplifying assumptions, can be applied to wild species reservoirs of zoonotic diseases in order to optimize the design of field studies to detect viruses. Furthermore, such models can contribute to assess the probability and timing of zoonotic outbreaks in human or livestock populations. This article illustrates one of the manifold applications of mathematical theory of disease epidemiology to optimize sampling of pathogens/parasites or vaccine development and release [7, 8]. The further coupling of such models with population genetics theory and statistical inference methods (using parasite genome data) increasingly provide insights into the adaptation and evolution of parasites to human, crops and livestock populations [9, 10].

References

[1] Pleydell D.R.J., Ndong Bass I., Mba Djondzo F.A., Djomsi D.M., Kouanfack C., Peeters M., and J. Cappelle. 2023. A Bayesian analysis of birth pulse effects on the probability of detecting Ebola virus in fruit bats. bioRxiv, ver. 3 peer reviewed and recommended by Peer Community In Infections. https://doi.org/10.1101/2023.08.10.552777

[2] Caron A., Bourgarel M., Cappelle J., Liégeois F., De Nys H.M., and F. Roger. 2018. Ebola virus maintenance: if not (only) bats, what else? Viruses 10, 549. https://doi.org/10.3390/v10100549

[3] Letko M., Seifert S.N., Olival K.J., Plowright R.K., and V.J. Munster. 2020. Bat-borne virus diversity, spillover and emergence. Nature Reviews Microbiology 18, 461–471. https://doi.org/10.1038/s41579-020-0394-z

[4] Leroy E.M., Kumulungui B., Pourrut X., Rouquet P., Hassanin A., Yaba P., Délicat A., Paweska J.T., Gonzalez J.P., and R. Swanepoel. 2005. Fruit bats as reservoirs of Ebola virus. Nature 438, 575–576. https://doi.org/10.1038/438575a

[5] Djomsi D.M. et al. 2022. Dynamics of antibodies to Ebolaviruses in an Eidolon helvum bat colony in Cameroon. Viruses 14, 560. https://doi.org/10.3390/v14030560

[6] Peel A.J. et al. 2016. Bat trait, genetic and pathogen data from large-scale investigations of African fruit bats Eidolon helvum. Scientific data 3, 1–11. https://doi.org/10.1038/sdata.2016.49

[7] Nyandjo Bamen H.L., Ntaganda J.M., Tellier A. and O. Menoukeu Pamen. 2023. Impact of imperfect vaccine, vaccine trade-off and population turnover on infectious disease dynamics. Mathematics, 11(5), p.1240. https://doi.org/10.3390/math11051240

[8] Saadi N., Chi Y.L., Ghosh S., Eggo R.M., McCarthy C.V., Quaife M., Dawa J., Jit M. and A. Vassall. 2021. Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review. BMC medicine, 19, pp.1-11. https://doi.org/10.1186/s12916-021-02190-3

[9] Maerkle, H., John S., Metzger, L., STOP-HCV Consortium, Ansari, M.A., Pedergnana, V. and Tellier, A., 2023. Inference of host-pathogen interaction matrices from genome-wide polymorphism data. bioRxiv, https://doi.org/10.1101/2023.07.06.547816.

[10] Gandon S., Day T., Metcalf C.J.E. and B.T. Grenfell. 2016. Forecasting epidemiological and evolutionary dynamics of infectious diseases. Trends in ecology & evolution, 31(10), pp.776-788. https://doi.org/10.1016/j.tree.2016.07.010

Trypanosoma lewisi is an atypical trypanosome species. Transmitted by fleas, it has a high prevalence and worldwide distribution in small mammals, especially rats [1]. Although not typically thought to infect humans, there has been a number of reports of human infections by T. lewisi in Asia including a case of a fatal infection in an infant [2]. The fact that the parasite is resistant to lysis by normal human serum [3] suggests that many people, especially immunocompromised individuals, may be at risk from zoonotic infections by this pathogen, particularly in regions where there is close contact with T. lewisi-infected rat fleas. Indeed, it is also possible that cryptic T. lewisi infections exist but have hitherto gone undetected. Such asymptomatic infections have been detected for a number of parasitic infections including the related parasite T. b. gambiense [4]. 
 
Despite the fact that T. lewisi parasites pose a risk to human health, very little is known about their population structure, reproductive mode, population size or dispersal. In the article [5], Ségard et al. presented the first attempt at examining the population structure of the parasite. They developed microsatellite markers and used them to analyse a small set of samples from West Africa and Southeast Asia. Although the number of microsatellite markers is not very high and they encountered problems of PCR amplification especially of the southeast Asian samples, they did provide preliminary data that hints at a clonal population structure with rare recombination and suggests population subdivisions occurring at a scale that is equal, and probably smaller than a neighborhood of several houses with a short generation time. These are very interesting preliminary findings that will need to be validated using a larger cohort with more markers or by whole genome sequencing.
 

References

[1] Hoare CA (1972) The trypanosomes of mammals. A zoological monograph. The trypanosomes of mammals. A zoological monograph.

[2] Truc P, Büscher P, Cuny G, Gonzatti MI, Jannin J, Joshi P, Juyal P, Lun Z-R, Mattioli R, Pays E, Simarro PP, Teixeira MMG, Touratier L, Vincendeau P, Desquesnes M (2013) Atypical Human Infections by Animal Trypanosomes. PLOS Neglected Tropical Diseases, 7, e2256. https://doi.org/10.1371/journal.pntd.0002256

[3] Lun Z-R, Wen Y-Z, Uzureau P, Lecordier L, Lai D-H, Lan Y-G, Desquesnes M, Geng G-Q, Yang T-B, Zhou W-L, Jannin JG, Simarro PP, Truc P, Vincendeau P, Pays E (2015) Resistance to normal human serum reveals Trypanosoma lewisi as an underestimated human pathogen. Molecular and Biochemical Parasitology, 199, 58–61. https://doi.org/10.1016/j.molbiopara.2015.03.007

[4] Büscher P, Bart J-M, Boelaert M, Bucheton B, Cecchi G, Chitnis N, Courtin D, Figueiredo LM, Franco J-R, Grébaut P, Hasker E, Ilboudo H, Jamonneau V, Koffi M, Lejon V, MacLeod A, Masumu J, Matovu E, Mattioli R, Noyes H, Picado A, Rock KS, Rotureau B, Simo G, Thévenon S, Trindade S, Truc P, Reet NV (2018) Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination? Trends in Parasitology, 34, 197–207. https://doi.org/10.1016/j.pt.2017.11.008

[5] Ségard A, Roméro A, Ravel S, Truc P, Gauthier D, Gauthier P, Dossou H-J, Sylvestre B, Houéménou G, Morand S, Chaisiri K, Noûs C, De Meeûs T (2022) Development of nine microsatellite loci for Trypanosoma lewisi, a potential human pathogen in Western Africa and South-East Asia, and preliminary population genetics analyses. Zenodo, 6460010, ver. 3 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.5281/zenodo.6460010