Deciphering the virome (the set or assemblage of viruses) of the Earth, from individual organisms to entire ecosystems, has become a key priority. The first step to better understanding the impact of viruses on the ecology and functions of ecosystems is to describe their diversity. Such knowledge opens the gates to a better assessment of global nutrient cycling or of the threat that viruses represent to individual health. This explains the increasing number of pioneering studies that are currently sequencing the complete or partial genome of thousands of new viruses [1].

In their exciting study, Fritz and collaborators [2], authors sampled 209 army ants (Genus Dorylus) to investigate the virus diversity in dense forests that researchers cannot easily access. Indeed, these ants live in colonies (21 were sampled) that can move 1 km per day, covering a significant area and attacking many invertebrate and vertebrate preys.  Each sample was sequenced by a protocol called VANA sequencing and allowing the enrichment of the sample in viral sequences [3], so improving the detection of viruses present at low abundance in the ant (and more specifically in its gut for viruses infecting preys). 

Around 45,000 contigs presented homologies with bacterial, plant, invertebrate, and vertebrate infecting viruses. Half could be assigned to 56 families and 157 genera of the International Committee on Taxonomy of Viruses. Beyond this amazing harvest of new and known virus sequences using an original methodology, the results significantly improve the current frontiers of known viral taxonomy and diversity and raise exciting research tracks to expand them. 

As a preprint, several blogs or news of leading scientists and journals have already highlighted this study. For example, in the news section of Science magazine, Jon Cohen underlined the originality of the approach for virus hunting on Earth with the title “Armed with air samplers, rope tricks, and—yes—ants, virus hunters spot threats in new ways”[4]. Another example is the mention of the publication by Elisabeth Bik in her Microbiome Digest: she wrote, “An amazing read is a fresh preprint from Fritz and collaborator describing an exciting method of sampling in difficult-to-reach environments“ [5].

The paper from Fritz et al [2] thus represents a significant advance in virus ecology, as already recognized by early readers, and this is why I strongly recommend its publication in PCI Infections.

REFERENCES

1. Edgar RC, Taylor J, Lin V, Altman T, Barbera P, Meleshko D, Lohr D, Novakovsky G, Buchfink B, Al-Shayeb B, Banfield JF, de la Peña M, Korobeynikov A, Chikhi R, Babaian A (2022) Petabase-scale sequence alignment catalyses viral discovery. Nature, 602, 142–147. https://doi.org/10.1038/s41586-021-04332-2

2. Fritz M, Reggiardo B, Filloux D, Claude L, Fernandez E, Mahé F, Kraberger S, Custer JM, Becquart P, Mebaley TN, Kombila LB, Lenguiya LH, Boundenga L, Mombo IM, Maganga GD, Niama FR, Koumba J-S, Ogliastro M, Yvon M, Martin DP, Blanc S, Varsani A, Leroy E, Roumagnac P (2023) African army ants at the forefront of virome surveillance in a remote tropical forest. bioRxiv, 2022.12.13.520061, ver. 4 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2022.12.13.520061

3. François S, Filloux D, Fernandez E, Ogliastro M, Roumagnac P (2018) Viral Metagenomics Approaches for High-Resolution Screening of Multiplexed Arthropod and Plant Viral Communities. In: Viral Metagenomics: Methods and Protocols Methods in Molecular Biology. (eds Pantaleo V, Chiumenti M), pp. 77–95. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7683-6_7

4. Cohen J (2023) Virus hunters test new surveillance tools. Science, 379, 16–17. https://doi.org/10.1126/science.adg5292

5. Ponsero A (2023) February 18th, 2023. Microbiome Digest - Bik’s Picks. https://microbiomedigest.com/2023/02/18/february-18th-2023/

African trypanosomiasis is caused by to the infection of a protozoan parasite of the Trypanosoma genus. It is transmitted by the tsetse fly, and is largely affecting cattle in the sub-humid areas of Africa, causing a high economic impact. However, not all the bovine strains are equally susceptible to the infection (1). 

In order to dissect the mechanisms underlying susceptibility to African trypanosoma infection, Peylhard et al (2) performed blood transcriptional profiles of trypanotolerant, trypanosensitive and mixed cattle breeds, before and after experimental infection with T. congolense. 

First of all, the authors have characterized the basal transcriptional profiles in the blood of the different breeds under study, which could be classified in a wide array of functional pathways. Of note, after infection some pathways were consistently enriched in all the group tested. Among them, the immune system-related ones were again on the top functions reported. The search for specific canonical pathways pointed to a prominent role of lipid and cholesterol-related pathways, as well as mitochondrial function and B and T lymphocyte activation.

However, the analysis of infected animals demonstrated that trypanosusceptible animals showed a stronger transcriptomic reprogramming, highly enriched in specific metabolic and immunological pathways. It is worthy to highlight striking differences in genes involved in immune signal transduction, cytokines and markers of different leukocyte subpopulations.

This work represents undoubtedly a significant momentum in the field, since the authors explore in deep a wide panel of cattle breeds representing the majority of West-African taurine and zebu in a systematic way. Since the animals were studied at different timepoints after infection, future longitudinal analyses of these datasets will be providing a precious insight on the kinetics of immune and metabolic reprogramming associated with susceptibility and tolerance to African trypanosoma infection, widening the application of this interesting study into new therapeutic interventions.

References

1. Berthier D, Peylhard M, Dayo G-K, Flori L, Sylla S, Bolly S, Sakande H, Chantal I, Thevenon S (2015) A Comparison of Phenotypic Traits Related to Trypanotolerance in Five West African Cattle Breeds Highlights the Value of Shorthorn Taurine Breeds. PLOS ONE, 10, e0126498. https://doi.org/10.1371/journal.pone.0126498

2. Peylhard M, Berthier D, Dayo G-K, Chantal I, Sylla S, Nidelet S, Dubois E, Martin G, Sempéré G, Flori L, Thévenon S (2022) Whole blood transcriptome profiles of trypanotolerant and trypanosusceptible cattle highlight a differential modulation of metabolism and immune response during infection by Trypanosoma congolense. bioRxiv, 2022.06.10.495622, ver. 2 peer-reviewed and recommended by Peer Community Infections. https://doi.org/10.1101/2022.06.10.495622.

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

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

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