Peek-A-Boo: “Hidden” Viruses in Protozoa Lead to Increased Illness Due to Evolutionary Advantages
As humans increase travel and connections around the world, so does concern about the spread of diseases, especially ones that are known to fail to respond to treatments. Scientists use genome sequencing to gain a better understanding of the Leishmania RNA virus, its host, Leishmania protozoa, and their relationship to the disease and failed treatment of Cutaneous leishmaniasis in humans.
Contact the author at izmeyers@davidson.edu
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Protozoa are microscopic organisms that have a wide range of roles in the environment. They can take the role of a parasite by living within other organisms, or they can become the host to viruses1. While not all protozoa are bad, there are some that contain viruses that cause serious disease in humans. One serious disease is cutaneous leishmaniasis, found mainly in the tropics, subtropics, and Southern Europe. Cutaneous leishmaniasis is caused by the Leishmania RNA virus that lives within Leishmania protozoa2 and is transmitted to humans through the bite of a female sandfly. Symptoms of this disease include skin lesions, open sores, irreversible scarring, and permanent disabilities3.
With no vaccine and around 2 million new cases per year3 affecting over 98 countries2, Cutaneous leishmaniasis remains an eminent threat to global health. One of the first steps to tackling a disease is to understand its hosts and how they evolve and spread around the globe. Recently, Heeren et al.2 investigated the ancestry and diversity of Leishmania protozoa and Leishmania RNA virus using genome sequencing data from Peru and Bolivia in hopes of understanding why certain patients with Cutaneous leishmaniasis do not respond to current treatments.
Heeren et al. first wanted to investigate the diversity among Leishmania populations. To do so, they sequenced the genomes (the complete set of genes in an organism) of samples collected from patients with Cutaneous leishmaniasis in health facilities in Peru and Bolivia. They found that there were different alleles (variations of a gene) among the Leishmania populations. Furthermore, the differences were seen among individuals in different geographical regions, suggesting that the environment may play a role in the genetic structure of the protozoa.
From these identified populations, Heeren et al. utilized grouping programs that divided the Leishmania populations into categories based on genome similarities. They found that, based on the similarities, the populations could be broadly grouped into two categories: ancestral populations and hybrid populations. Each ancestral population was a cluster with very little variation between each organism in the population. Hybrid populations were groups whose organisms were of mixed ancestry, meaning their genome contained genetic information from two different ancestral populations. Heeren et al. discovered that the ancestral populations were geographically isolated within the Amazonian Rainforest, while the hybrid populations were geographically distributed. This isolation of the ancestral populations suggests that Leishmania evolved from the Amazonian Rainforest. Hybrid populations were created as the ancestral populations adapted to changes in forestation of the rainforest and learned to interact with the wide variety of organisms that inhabit the area.
After looking at the host, Heeren et al. was interested in which populations were infected with Leishmania RNA virus. Leishmania RNA virus is a Totivirus, and this group of viruses is known for lying dormant in cells. This dormancy allows the virus to remain undetected and so permits long-term existence within its host. This virus has a mutualistic relationship with Leishmania, which means that both the virus and its host benefit from each other. The Totivirus cannot survive without a host, and its presence in Leishmania grants the protozoa enhanced virulence (severity or harmfulness of disease) and survival advantage2. They found that the majority of the sequenced Leishmania RNA virus genomes were from hybrid individuals. Furthermore, hybrid Leishmania were commonly infected with multiple strains of Leishmania RNA virus, while the ancestral populations were rarely infected with Leishmania RNA virus at all. If an ancestral population was infected, it was with only one Leishmania RNA virus strain.
Most concerningly, the majority of patients who had treatment failure for Cutaneous leishmaniasis were infected with hybrid Leishmania. This suggests that patients have a greater risk of treatment failure if they are infected with hybrid Leishmania parasites, although Heeren et al. does warn that they will need to investigate a larger sample size to statistically confirm these findings. It is best to include a wider diversity of samples, as this will help uncover more hybrid strains that may differ in their reaction to medical treatments. These findings indicate that environmental changes and migration of both humans and hosts have led to the spread of Leishmania and their viruses out of the Amazonian Rainforest. Since this disease mainly manifests in tropical regions, the individuals affected have been historically underrepresented in medical research. Therefore, it is vital to continue research in these areas to help increase medical equality around the world. Furthermore, as people continue to move about the world, it is important to keep in mind the global implications of such travel. It is especially important to monitor the spread of the hybrid strains, as they increase the risk of Cutaneous leishmaniasis treatment failure and remain a prevalent public health concern.
References
1. Solomon, R. et al. Protozoa populations are ecosystem engineers that shape prokaryotic community structure and function of the rumen microbial ecosystem. ISME J. 16, 1187–1197 (2022). Article
2. Heeren, S. et al. Diversity and dissemination of viruses in pathogenic protozoa. Nat. Commun. 14, 8343 (2023). Article
3. de Vries, H. J. C. & Schallig, H. D. Cutaneous Leishmaniasis: A 2022 Updated Narrative Review into Diagnosis and Management Developments. Am. J. Clin. Dermatol. 23, 823–840 (2022). Article
I liked how you summarized the study, Isabelle! Something really interesting about protozoa is that they are currently affecting so many countries as I’ve never heard about this virus before. I wonder how Leishmania evolved from the Amazonian rainforest, could it be because of the ecosystems surrounding it? For the results, there could be a possibility that ancestral populations were rarely infected with Leishmania RNA Virus due to past mutations or selective genes passed through generations. Additionally, I agree that it is vital to increase medical equality, Peru and Bolivia have a scarce amount of health resources that could hinder the ability of finding cures for such viruses.
This was such an interesting article! I had never heard of Leishmania, and upon looking it up, it seems like it would be very painful. Your paper reintroduced me to some topics that I had forgotten about, such as RNA viruses, protozoa, and hosts. Hopefully, these papers encourage more research into Leishmania, especially since it can affect so many people in underrepresented regions. Perhaps people will be made more aware about the impact of travel on disease, specifically the evolution of viruses, after reading your paper.
Hi Izzie, thanks for the great insights on Leishmana. It would be interesting to know more about the mechanism behind why the parasites of mixed ancestry are more virulent. Did the researchers identify any pathogenicity islands or virulence factors that are or are not present in two groups? Also, is there any gene transfer between the virus and the protozoan?
I agree with your comments on the relevance to public health. Leishmaniasis will likely be an increasingly prevalent illness, even in new populations, as climate change affects the geographic distribution of these protozoa. We definitely need to gain a better understanding of what’s going on in this study so that we can improve our treatments.
Again, nicely done, and great job writing in a layperson-accessible manner.