Evolutionary Dynamics of Giant Viruses and their Virophages

Giant viruses contain large genomes, encode many proteins atypical for viruses, replicate in large viral factories, and tend to infect protists. The giant virus replication factories can in turn be infected by so called virophages, which are smaller viruses that negatively impact giant virus replication. An example are Mimiviruses that infect the protist Acanthamoeba and that are themselves infected by the virophage Sputnik. This paper examines the evolutionary dynamics of this system, using mathematical models. While the models suggest that the virophage population will evolve to increasing degrees of giant virus inhibition, it further suggests that this renders the virophage population prone to extinction due to dynamic instabilities over wide parameter ranges. Implications and conditions required to avoid extinction are discussed. Another interesting result is that virophage presence can fundamentally alter the evolutionary course of the giant virus. While the giant virus is predicted to evolve towards increasing its basic reproductive ratio in the absence of the virophage, the opposite is true its presence. Therefore, virophages can not only benefit the host population directly by inhibiting the giant viruses, but also indirectly by causing giant viruses to evolve towards weaker phenotypes. Experimental tests for this model are suggested

Computational tools for viral metagenomics and their application in clinical research

AbstractThere are 100 times more virions than eukaryotic cells in a healthy human body. The characterization of human-associated viral communities in a non-pathological state and the detection of viral pathogens in cases of infection are essential for medical care and epidemic surveillance. Viral metagenomics, the sequenced-based analysis of the complete collection of viral genomes directly isolated from an organism or an ecosystem, bypasses the “single-organism-level” point of view of clinical diagnostics and thus the need to isolate and culture the targeted organism. The first part of this review is dedicated to a presentation of past research in viral metagenomics with an emphasis on human-associated viral communities (eukaryotic viruses and bacteriophages). In the second part, we review more precisely the computational challenges posed by the analysis of viral metagenomes, and we illustrate the problem of sequences that do not have homologs in public databases and the possible approaches to characterize them

Vimentin: from a cytoskeletal protein to a critical modulator of immune response and a target for infection

Vimentin is an intermediate filament protein that plays a role in cell processes, including cell migration, cell shape and plasticity, or organelle anchorage. However, studies from over the last quarter-century revealed that vimentin can be expressed at the cell surface and even secreted and that its implications in cell physiology largely exceed structural and cytoskeletal functions. Consequently, vimentin contributes to several pathophysiological conditions such as cancer, autoimmune and inflammatory diseases, or infection. In this review, we aimed at covering these various roles and highlighting vimentin implications in the immune response. We also provide an overview of how some microbes including bacteria and viruses have acquired the ability to circumvent vimentin functions in order to interfere with host responses and promote their uptake, persistence, and egress from host cells. Lastly, we discuss the therapeutic approaches associated with vimentin targeting, leading to several beneficial effects such as preventing infection, limiting inflammatory responses, or the progression of cancerous events

Hybrid Capture-Based Next Generation Sequencing and Its Application to Human Infectious Diseases

This review describes target-enrichment approaches followed by next generation sequencing and their recent application to the research and diagnostic field of modern and past infectious human diseases caused by viruses, bacteria, parasites and fungi

Diazotroph community succession during the VAHINE mesocosm experiment (New Caledonia lagoon)

The VAHINE mesocosm experiment, conducted in the low-nutrient low-chlorophyll waters of the Noumea lagoon (coastal New Caledonia) was designed to trace the incorporation of nitrogen (N) fixed by diazotrophs into the food web, using large volume (50 m(3)) mesocosms. This experiment provided a unique opportunity to study the succession of different N-2-fixing microorganisms (diazotrophs) and calculate in situ net growth and mortality rates in response to fertilization with dissolved inorganic phosphate (DIP) over a 23-day period, using quantitative polymerase chain reaction (qPCR) assays targeting widely distributed marine diazotroph lineages. Inside the mesocosms, the most abundant diazotroph was the heterocyst-forming Richelia associated with Rhizosolenia (Het-1) in the first half of the experiment, while unicellular cyanobacterial Group C (UCYN-C) became abundant during the second half of the experiment. Decreasing DIP concentrations following the fertilization event and increasing temperatures were significantly correlated with increasing abundances of UCYN-C. Maximum net growth rates for UCYN-C were calculated to range between 1.23 +/- 0.07 and 2.16 +/- 0.07 d(-1) in the mesocosms, which are among the highest growth rates reported for diazotrophs. Outside the mesocosms in the New Caledonia lagoon, UCYN-C abundances remained low, despite increasing temperatures, suggesting that the microbial community response to the DIP fertilization created conditions favorable for UCYN-C growth inside the mesocosms. Diazotroph community composition analysis using PCR targeting a component of the nitrogenase gene (nifH) verified that diazotrophs targeted in qPCR assays were collectively among the major lineages in the lagoon and mesocosm samples, with the exception of Crocosphaera-like phylotypes, where sequence types not typically seen in the oligotrophic ocean grew in the mesocosms. Maximum net growth and mortality rates for nine diazotroph phylotypes throughout the 23-day experiment were variable between mesocosms, and repeated fluctuations between periods of net growth and mortality were commonly observed. The field population of diazotrophs in the New Caledonian lagoon waters appeared to be dominated by Het-1 over the course of the study period. However, results from both qPCR and PCR analysis indicated a diverse field population of diazotrophs was present in the lagoon at the time of sampling. Two ecotypes of the Braarudosphaera bigelowii symbiont unicellular group A (UCYN-A) were present simultaneously in the lagoon, with the recently described B. bigelowii/UCYN-A2 association present at higher abundances than the B. bigelowii/UCYN-A1 association

Whipple's Disease: a Macrophage Disease

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Tropheryma whipplei, the Whipple's disease bacillus, induces macrophage apoptosis through the extrinsic pathway

Tropheryma whipplei, the etiological agent of Whipple's disease, is an intracellular bacterium that infects macrophages. We previously showed that infection of macrophages results in M2 polarization associated with induction of apoptosis and interleukin (IL)-16 secretion. In patients with Whipple's disease, circulating levels of apoptotic markers and IL-16 are increased and correlate with the activity of the disease. To gain insight into the understanding of the pathophysiology of this rare disease, we examined the molecular pathways involved in T. whipplei-induced apoptosis of human macrophages. Our data showed that apoptosis induction depended on bacterial viability and inhibition of bacterial protein synthesis reduced the apoptotic program elicited by T. whipplei. Induction of apoptosis was also associated with a massive degradation of both pro- and anti-apoptotic mediators. Caspase-specific inhibition experiments revealed that initiator caspases 8 and 10 were required for apoptosis, in contrast to caspases 2 and 9, in spite of cytochrome-c release from mitochondria. Finally, the effector caspases 3 and 6 were mandatory for apoptosis induction. Collectively, these data suggest that T. whipplei induces apoptosis through the extrinsic pathway and that, beside M2 polarization of macrophages, apoptosis induction contributes to bacterial replication and represents a virulence trait of this intracellular pathogen

Pepper Mild Mottle Virus, a Plant Virus Associated with Specific Immune Responses, Fever, Abdominal Pains, and Pruritus in Humans

Background: Recently, metagenomic studies have identified viable Pepper mild mottle virus (PMMoV), a plant virus, in the stool of healthy subjects. However, its source and role as pathogen have not been determined. Methods and Findings: 21 commercialized food products containing peppers, 357 stool samples from 304 adults and 208 stool samples from 137 children were tested for PMMoV using real-time PCR, sequencing, and electron microscopy. Anti-PMMoV IgM antibody testing was concurrently performed. A case-control study tested the association of biological and clinical symptoms with the presence of PMMoV in the stool. Twelve (57%) food products were positive for PMMoV RNA sequencing. Stool samples from twenty-two (7.2%) adults and one child (0.7%) were positive for PMMoV by real-time PCR. Positive cases were significantly more likely to have been sampled in Dermatology Units (p<10−6), to be seropositive for anti-PMMoV IgM antibodies (p = 0.026) and to be patients who exhibited fever, abdominal pains, and pruritus (p = 0.045, 0.038 and 0.046, respectively). Conclusions: Our study identified a local source of PMMoV and linked the presence of PMMoV RNA in stool with a specific immune response and clinical symptoms. Although clinical symptoms may be imputable to another cofactor, including spicy food, our data suggest the possibility of a direct or indirect pathogenic role of plant viruses in humans

Metagenomic Analysis Indicates that Stressors Induce Production of Herpes-Like Viruses in Coral \u3cem\u3ePorites compressa\u3c/em\u3e

During the last several decades corals have been in decline and at least one-third of all coral species are now threatened by extinction. Coral disease has been a major contributor to this threat, but little is known about the responsible pathogens. To date most research has focused on bacterial and fungal diseases; however, viruses may also be important for coral health. Using a combination of empirical viral metagenomics and real-time PCR, we show that Porites compressa corals contain a suite of eukaryotic viruses, many related to the Herpesviridae. This coral-associated viral consortium was found to shift in response to abiotic stressors. In particular, when exposed to reduced pH, elevated nutrients, and thermal stress, the abundance of herpes-like viral sequences rapidly increased in 2 separate experiments. Herpes-like viral sequences were rarely detected in apparently healthy corals, but were abundant in a majority of stressed samples. In addition, surveys of the Nematostella and Hydra genomic projects demonstrate that even distantly related Cnidarians contain numerous herpes-like viral genes, likely as a result of latent or endogenous viral infection. These data support the hypotheses that corals experience viral infections, which are exacerbated by stress, and that herpes-like viruses are common in Cnidarians

Expanding networks of RNA virus evolution

In a recent BMC Evolutionary Biology article, Huiquan Liu and colleagues report two new genomes of double-stranded RNA (dsRNA) viruses from fungi and use these as a springboard to perform an extensive phylogenomic analysis of dsRNA viruses. The results support the old scenario of polyphyletic origin of dsRNA viruses from different groups of positive-strand RNA viruses and additionally reveal extensive horizontal gene transfer between diverse viruses consistent with the network-like rather than tree-like mode of viral evolution. Together with the unexpected discoveries of the first putative archaeal RNA virus and a RNA-DNA virus hybrid, this work shows that RNA viral genomics has major surprises to deliver