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

Détection et impact potentiel des tobamovirus chez l’homme

A current paradigm in virology is that plant viruses cannot affect vertebrates and are not pathogenic for humans. However, several recent findings challenge this paradigm.Thus, plant viruses can be present in invertebrates, but also in vertebrates, and that this presence may be non neutral. First, sorne plant and animal viroses belong to same viral families, and can harbor almost identical gene repertoires. Second, there are many examples of plant viroses that circulate and multiply in insects. Third, plant viroses have been detected in vertebrates, including humans. Indeed, recent metagenomic studies showed that plant viruses were predominant RNA viruses in human stools. Fourth, immune responses against plant viroses have been detected in animals and humans. Finally, the presence of plant viroses in animais and humans may be non neutral, and some works have suggested their pathogenicity for insects and humans. The aim of this thesis was to investigate whether tobamoviruses may be pathogenic in humans. The first part of my work is a review of the literature of the reasons why plant viruses may cross the border from plants to vertebrates and on the presence and possible impact of these viruses in animals including humans. The second part focuses on exposure to tobamoviros and possible effects of these viroses for humans. In the Marseille geographical area, we showed the presence of Pepper mild mottle virus (PMMoV) in 7.2% of stools from patients tested and in 57% of food products containing hot peppers. In addition, PMMoV from food items was still infectious for plants and the presence of PMMoV in the stools of patients could be significantly associated with a specific immune response and clinical symptoms including fever, abdominal pain and pruritus. Then, we showed that TMV was present in the tobacco of all cigarettes tested and was infectious from half of the cigarettes. In addition, TMV RNA was detected in 45% of smokers' saliva that we tested. The third part of this manuscript focuses on the study of a possible pathogenic role of tobamoviroses, in particular TMV, for vertebrate animais through the use of mouse and cellular experimental models. We inoculated TMV by the intra-tracheal way to mice to mimic exposure to TMV-infected tobacco and TMV was also inoculated to murine macrophages. The results showed the persistence until 14 days of viroses in the lung tissue and in lung alveolar macrophages of mice. In addition, we detected TMV in the cytoplasm of murine macrophages up to 15 days after inoculation. In summary, our results suggest that the boundary between plant viroses and animal viroses is not as strict as it is commonly accepted and prompt to reassess the potential pathogenicity of these plant viroses for humans, especially in prospect of the use of vaccines with recombinant plant viroses.Un paradigme actuel en virologie est que les virus de plantes ne peuvent pas affecter les animaux vertébrés et ne sont pas pathogènes pour 1'homme, qui est pourtant exposé quotidiennement à ces virus. Cependant, plusieurs éléments remettent en question ce paradigme. Ainsi, les virus de plantes peuvent être présents chez les invertébrés, mais aussi chez des vertébrés, et cette présence pourrait ne pas être neutre. Premièrement, certains virus végétaux et animaux appartiennent à de mêmes familles et peuvent posséder des répertoires de gènes quasi-identiques. Deuxièmement, il existe de nombreux exemples de phytovirus qui circulent et se multiplient chez les insectes. Troisièmement, des virus de plantes ont été détectés chez les animaux vertébrés, y compris chez l'homme. En particulier, des études récentes de métagénomique portant sur le virome intestinal humain ont mis en évidence que des virus de plantes étaient très majoritaires dans les selles. Quatrièmement, des réponses immunitaires contre des virus de plantes ont été détectées chez des animaux et chez l'homme. De plus, la présence des virus de plantes chez les animaux et l'homme pourraient ne pas être neutre, et des travaux ont suggéré leur pathogénicité chez les insectes et l'homme. L'objectif de cette Thèse a été d'étudier si les tobamovirus peuvent être pathogènes chez l'homme. La première partie de mon travail correspond à une revue de la littérature portant sur la présence et l'impact potentiel des virus de plantes chez les animaux dont l'homme. La seconde partie porte sur l'exposition aux tobamovirus et les effets possibles de ces virus des tobamovirus chez l'homme. Dans la région de Marseille, nous avons montré la présence du Pepper mild mottle virus (PMMoV) dans 7.2% des selles de patients et dans 57% des produits alimentaires à base de piment. De plus, le PMMoV peut rester infectieux dans les aliments et la présence du PMMoV dans les selles de patients a pu être associée de façon significative à une réponse immunitaire spécifique et des signes cliniques (fièvres, douleurs abdominales ou prurit). De plus, nous avons montré que le Tobacco mosaic virus (TMV) était présent dans le tabac de toutes les cigarettes testées et restait infectieux dans une cigarette sur 2. Par ailleurs, nous avons montré que ce virus était retrouvé dans 45% des salives de fumeurs testées. La troisième partie de ce travail porte sur l'étude d'un éventuel rôle pathogène des tobamovirus, notamment le TMV, pour les animaux vertébrés, via l'utilisation de modèles expérimentaux murin et cellulaire. Nous avons inoculé des particules virales de TMV à des souris par voie intra-trachéale afm de mimer l'exposition au TMV via le tabac de cigarette, et avons également inoculé du TMV à des macrophages murins. Les résultats ont montré chez la souris une persistance du virus jusqu'à 14 jours dans le tissu pulmonaire et les macrophages pulmonaires. De plus, nous avons détecté du TMV dans le cytoplasme des macrophages murins jusqu'à 15 jours après inoculation. En résumé, nos résultats suggèrent que la frontière entre virus de plantes et virus d'animaux n'est pas aussi stricte qu'il est communément admis et incitent à ré-évaluer l'éventuel pathogénicité des phytovirus pour l'homme, particulièrement dans la perspective d'une utilisation vaccinale de virus de plantes recombinants

Detection and potential impact of Tobamovirus in humans

Un paradigme actuel en virologie est que les virus de plantes ne peuvent pas affecter les animaux vertébrés et ne sont pas pathogènes pour l'homme. Cependant, plusieurs éléments remettent en question ce paradigme. L'objectif de cette Thèse a été d'étudier si les tobamovirus peuvent être pathogènes chez l'homme. Ce manuscrit comprend :1) une revue de la littérature portant sur la présence et l'impact potentiel des virus de plantes chez les animaux dont l'homme. 2) une étude sur l'exposition humaine aux tobamovirus et les effets possibles Dans la région de Marseille, nous avons montré la présence du PMMoV dans 7.2% des selles de patients et dans 57 % des produits alimentaires à base de piment. De plus, la présence du PMMoV dans les selles de patients a pu être corrélée des signes cliniques. De plus, nous avons montré que le TMV infectieux était présent dans le tabac de toutes les cigarettes testées mais aussi dans 45 % des salives de fumeurs testées. 3) une étude in vivo. Suite à une inoculation intra-trachéal des souris avec du TMV, nous avons constaté que le virus persiste jusqu'à 14 jours dans le tissu pulmonaire et les macrophages pulmonaires. De plus, nous avons détecté du TMV dans le cytoplasme des macrophages murins jusqu'à 15 jours après inoculation. 4) une étude sur le mode de transmission du TMV à l'homme. Le TMV détecté dans la salive des fumeurs ne serait pas véhiculé par la fumée de cigarette, mais par contact avec du tabac infecté. Nos résultats suggèrent que la frontière entre virus de plantes et virus d'animaux n'est pas aussi stricte qu'il est communément admis et incitent à réévaluer l'éventuelle pathogénicité des phytovirus pour l'homme.A current paradigm in virology is that plant viruses cannot affect vertebrates and are not pathogenic for humans. However, several recent findings challenge this paradigm. The aim of this thesis was to investigate whether tobamoviruses may be pathogenic in humans. This manuscript contains: 1) A review of the literature of the reasons why plant viruses may cross the border from plants to vertebrates and the possible impact of plant viruses in animals including humans. 2) A study on exposure to tobamovirus and possible effects of these viruses for humans. In the Marseille geographical area, we showed the presence PMMoV in 7.2% of stools from patients tested and in 57% of food products containing hot peppers. In addition, the presence of PMMoV in the stools of patients could be significantly correlated with clinical symptoms. Then, we showed that infectious TMV was present in the tobacco of all cigarettes tested and TMV RNA was detected in 45% of smokers' saliva tested. 3) In vivo study: mice intra-tracheal inoculation with TMV. The results showed the persistence until 14 days of viruses in the lung tissue and in lung alveolar macrophages of mice. In addition, we detected TMV in the cytoplasm of murine macrophages up to 15 days after inoculation. 4) A study of TMV transmission to humans through cigarette smoking. TMV does not seem to be vehicled by cigarette smoke to smoker's saliva but by direct contact with infected tobacco. Our results suggest that the boundary between plant viruses and animal viruses is not as strict as it is commonly accepted and prompt to reassess the potential pathogenicity of these plant viruses for humans

Can Plant Viruses Cross the Kingdom Border and Be Pathogenic to Humans?

Phytoviruses are highly prevalent in plants worldwide, including vegetables and fruits. Humans, and more generally animals, are exposed daily to these viruses, among which several are extremely stable. It is currently accepted that a strict separation exists between plant and vertebrate viruses regarding their host range and pathogenicity, and plant viruses are believed to infect only plants. Accordingly, plant viruses are not considered to present potential pathogenicity to humans and other vertebrates. Notwithstanding these beliefs, there are many examples where phytoviruses circulate and propagate in insect vectors. Several issues are raised here that question if plant viruses might further cross the kingdom barrier to cause diseases in humans. Indeed, there is close relatedness between some plant and animal viruses, and almost identical gene repertoires. Moreover, plant viruses can be detected in non-human mammals and humans samples, and there are evidence of immune responses to plant viruses in invertebrates, non-human vertebrates and humans, and of the entry of plant viruses or their genomes into non-human mammal cells and bodies after experimental exposure. Overall, the question raised here is unresolved, and several data prompt the additional extensive study of the interactions between phytoviruses and non-human mammals and humans, and the potential of these viruses to cause diseases in humans

Tobacco mosaic virus in cigarettes and saliva of smokers

International audienceBackground:Tobacco mosaic virus (TMV) has been described as viable in cigarettes or cigar tobacco. It has been cultured about 50 years ago from sputa and thoracentesis fluids of cigarette smokers with a history of pulmonary disease and from lung cancerous matter. In addition, TMV RNA has been recovered recently from human stools while tobacco DNA was recovered from smokers’ bronchoalveolar lavages. Objectives:We assessed the prevalence, titers, and infectivity of TMV in tobacco cigarettes and in the saliva of smokers and non smokers. Study design:Tobacco cigarettes from 10 packs of different brands were purchased. Saliva was collected from 12 smokers and 15 non-smokers. Cigarettes and saliva samples were tested for the presence of TMV RNA using a home-made quantitative real-time RT-PCR assay. TMV RNA quantification was enabled by using dilutions of purified TMV. TMV viability was tested by inoculating leaves of Nicotiana tabacum Xanthi (NtX). Results: All 47 smoking cigarettes of six brands were TMV RNA-positive (mean titer, 9.5 log10 copies/cigarette); TMV was found viable in 53% of them. In addition, 20/44 (45%) saliva from 12 smokers compared to 0/16 saliva from 15 non-smokers tested positive for TMV RNA (mean titer, 3.8 log10 copies/ml) (p = 0.001). Conclusions: Our results indicate that the TMV genome may get access to the human body by direct exposure through smoking. Although plant viruses are considered not pathogenic for animals, these data prompt to study if TMV RNA is present and induces a modification of the transcriptional program in lung cells of cigarette smokers

Can plant viruses cross the kingdom border and be pathogenic to humans?

Phytoviruses are highly prevalent in plants worldwide, including vegetables and fruits. Humans, and more generally animals, are exposed daily to these viruses, among which several are extremely stable. It is currently accepted that a strict separation exists between plant and vertebrate viruses regarding their host range and pathogenicity, and plant viruses are believed to infect only plants. Accordingly, plant viruses are not considered to present potential pathogenicity to humans and other vertebrates. Notwithstanding these beliefs, there are many examples where phytoviruses circulate and propagate in insect vectors. Several issues are raised here that question if plant viruses might further cross the kingdom barrier to cause diseases in humans. Indeed, there is close relatedness between some plant and animal viruses, and almost identical gene repertoires. Moreover, plant viruses can be detected in non-human mammals and humans samples, and there are evidence of immune responses to plant viruses in invertebrates, non-human vertebrates and humans, and of the entry of plant viruses or their genomes into non-human mammal cells and bodies after experimental exposure. Overall, the question raised here is unresolved, and several data prompt the additional extensive study of the interactions between phytoviruses and non-human mammals and humans, and the potential of these viruses to cause diseases in humans

Le Pepper mild mottle virus (PMMoV) et le Tobacco mosaic virus (TMV) présentent-ils un risque pour la santé humaine?

National audienc

Can Plant Viruses Cross the Kingdom Border and Be Pathogenic to Humans?

Phytoviruses are highly prevalent in plants worldwide, including vegetables and fruits. Humans, and more generally animals, are exposed daily to these viruses, among which several are extremely stable. It is currently accepted that a strict separation exists between plant and vertebrate viruses regarding their host range and pathogenicity, and plant viruses are believed to infect only plants. Accordingly, plant viruses are not considered to present potential pathogenicity to humans and other vertebrates. Notwithstanding these beliefs, there are many examples where phytoviruses circulate and propagate in insect vectors. Several issues are raised here that question if plant viruses might further cross the kingdom barrier to cause diseases in humans. Indeed, there is close relatedness between some plant and animal viruses, and almost identical gene repertoires. Moreover, plant viruses can be detected in non-human mammals and humans samples, and there are evidence of immune responses to plant viruses in invertebrates, non-human vertebrates and humans, and of the entry of plant viruses or their genomes into non-human mammal cells and bodies after experimental exposure. Overall, the question raised here is unresolved, and several data prompt the additional extensive study of the interactions between phytoviruses and non-human mammals and humans, and the potential of these viruses to cause diseases in humans

Emergence of Wesselsbron virus among black rat and humans in Eastern Senegal in 2013

International audienceWesselsbron disease is a neglected mosquito transmitted Flavivirus infection that causes abortions and has tera-togenic effects on sheep and cattle in Africa. Human can also be infected. The detection of human or animal cases is complicated by the non-specific symptoms close to Rift Valley Fever (RVF) in domestic livestock species or Dengue like syndrome in humans. Then, these detections are usually made during RVF investigations in sheep. These domestic animals should take a role in the life cycle of the virus but some evidences of Wesselsbron virus (WSLV) presence in wild animals suggest that the latter may be involved in the virus maintenance in nature. However, the reservoir status of wild vertebrate in general and rodents particularly for WSLV is only based on an isolation from a Cape short-eared gerbil in southern Africa. Most of WSLV isolations are from southern parts of Africa even if it has been found in western and central Africa or Madagascar. In Senegal, there are serological evidences of WSLV circulation in human since the 1970s and some isolations, the last one of which dates back in 1992. Despite the detection of the virus on mosquitoes until the 2000s in different parts of the country, no new human case has been noted. In this paper, we report the WSLV re-emergence in eastern Senegal in 2013 with 2 human cases and its first isolation from a black rat Rattus rattus. Sequencing analyses show the circulation of the same strain between these humans and the commensal rodent. The putative impact on WSLV transmission to human populations could be more important if the reservoir status of the black rat is confirmed. Focused survey in human populations, specific entomological and mammalogical investigations would permit a better understanding of the life cycle of the virus and its impact on public health