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Marion Desdouits,
Olivier Cassar,
Thierry Maisonobe,
Alexandra Desrames,
Achille Aouba,
Olivier Hermine,
Jacqueline Mikol,
Marc Polivka,
Isabelle Penisson-Besnier,
Pascale Marcorelles, [......],
Eric Wattel,
Michel Huerre,
Marie-Christine Cumont,
Sandra Martin-Latil,
Gillian Butler-Browne,
Olivier Gout,
Graham Taylor, Antoine Gessain,
Simona Ozden,
Pierre-Emmanuel Ceccaldi
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ABSTRACT: BACKGROUND: The Human T-cell Leukemia Virus type 1 (HTLV-1) is the causative agent of several inflammatory diseases, including HTLV-1-associated inflammatory myopathies (HAIM). Little is known about the virological and immunological characteristics of this viral disease. OBJECTIVES: To characterize the histological and virological features of HAIM patients, in order to better understand the pathogenetic mechanisms and unravel new biological markers of this disease. STUDY DESIGN: We conducted a retrospective study on 13 patients with HAIM, based on blood and muscle samples. We included blood samples from HTLV-1-infected individuals without myopathy as controls. Muscle biopsies were used for a broad immunohistological evaluation of tissue damage and inflammation, as well as identification of infected cells through in situ hybridization. DNA extracted from patients' PBMC was used to identify the virus genotype by sequencing and to assess the proviral load by quantitative PCR. Anti-viral antibodies in plasma samples were titrated by indirect immunofluorescence. RESULTS: Patients originate from HTLV-1 endemic areas, the West Indies and West Africa. Histological alterations and inflammation in patients muscles were mostly moderate, with classical features of idiopathic myositis and rare HTLV-1-infected infiltrating cells. In all patients, HTLV-1 belonged to the A subtype, transcontinental subgroup. Anti-HTLV-1 antibodies titers were high, but the proviral load was not elevated compared to asymptomatic HTLV-1 carriers. CONCLUSION: We show here that muscle inflammation is moderate in HAIM, and accompanied by a low HTLV-1 proviral load, suggesting that the pathogenetic events do not exactly mirror those of other HTLV-1-associated inflammatory diseases.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 01/2013; · 3.12 Impact Factor
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ABSTRACT: Non-human primates are considered to be likely sources of viruses that can infect humans and thus pose a significant threat to human population. This is well illustrated by some retroviruses, as the simian immunodeficiency viruses and the simian T lymphotropic viruses, which have the ability to cross-species, adapt to a new host and sometimes spread. This leads to a pandemic situation for HIV-1 or an endemic one for HTLV-1. Here, we present the available data on the discovery, epidemiology, cross-species transmission and molecular virology of the recently discovered HTLV-3 and HTLV-4 deltaretroviruses, as well as the simian foamy retroviruses present in different human populations at risk, especially in central African hunters. We discuss also the natural history in humans of these retroviruses of zoonotic origin (magnitude and geographical distribution, possible inter-human transmission). In Central Africa, the increase of the bushmeat trade during the last decades has opened new possibilities for retroviral emergence in humans, especially in immuno-compromised persons.
Virology 01/2013; 435(1):187-199. · 3.35 Impact Factor
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Juliette Paireau,
Nguyen Hai Tuan,
Rémi Lefrançois,
Matthew R Buckwalter,
Ngu Duy Nghia,
Nguyen Tran Hien,
Olivier Lortholary,
Sylvain Poirée,
Jean-Claude Manuguerra, Antoine Gessain,
Matthew L Albert,
Paul T Brey,
Phan Thi Nga,
Arnaud Fontanet
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ABSTRACT: Since the end of the 1990s, unexplained outbreaks of acute encephalitis in children coinciding with litchi harvesting (May-July) have been documented in the Bac Giang Province in northern Vietnam. A retrospective ecologic analysis of data for 2004-2009 involving environmental, agronomic, and climatic factors was conducted to investigate the suspected association between the outbreaks and litchi harvesting. The clinical, biological, and immunologic characteristics of the patients suggested a viral etiology. The ecologic study revealed an independent association between litchi plantation surface proportion and acute encephalitis incidence: Incidence rate ratios were 1.52 (95% CI 0.90-2.57), 2.94 (95% CI 1.88-4.60), and 2.76 (95% CI 1.76-4.32) for second, third, and fourth quartiles, respectively, compared with the lowest quartile. This ecologic study confirmed the suspected association between incidence of acute encephalitis and litchi plantations and should be followed by other studies to identify the causative agent for this syndrome.
Emerging Infectious Diseases 11/2012; 18(11):1817-24. · 6.79 Impact Factor
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ABSTRACT: Simian foamy viruses (SFV) are widespread retroviruses among non-human primates (NHP). SFV actively replicates in their oral cavity and can be transmitted to humans after NHP bites, giving rise to a persistent infection even decades after primary infection. Very few data are available on the genetic structure of such SFV found in humans.In the framework of ongoing studies searching for SFV-infected humans in South Cameroon rainforest villages, we studied 38 SFV-infected hunters whose time of infection were presumably determined. By long-term co-cultures of PBMCs with BHK-21 cells, we isolated 5 new SFV strains, providing complete genomes of SFVcpz Pan troglodytes troglodytes (BAD327, AG15), SFVcni Cercopithecus nictitans (AG16) and SFVggo Gorilla gorilla (BAK74 and BAD468). These zoonotic strains share a very high similarity with their NHP counterparts with a high conservation of the genetic elements important for viral replication. Interestingly, FV DNA sequences obtained before cultivation revealed in both U3 and tas some deletion variants that may correlate with in vivo chronicity in humans. Genomic changes in bet (premature stop codon) and gag were also observed. To know if such changes were specific to zoonotic strains, we studied local SFV-infected chimpanzees and found the same genomic changes.Our study reveals that natural polymorphism of SFV strains does exist, at both inter-subspecies level (gag, bet) and intra-subspecies level (U3, tas) but seems not to reflect a viral adaptation specific to zoonotic SFV strains.
Journal of Virology 09/2012; · 5.40 Impact Factor
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Jussi Sane,
Satu Kurkela,
Marion Desdouits,
Hannu Kalimo,
Simon Mazalrey,
Marja-Liisa Lokki,
Antti Vaheri,
Tapani Helve,
Jyrki Törnwall,
Michel Huerre,
Gillian Butler-Browne,
Pierre-Emmanuel Ceccaldi, Antoine Gessain,
Olli Vapalahti
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ABSTRACT: Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection is characterized by febrile rash and arthritis and sometimes prolonged arthralgia and myalgia. The pathophysiological mechanisms of musculoskeletal and rheumatic disease caused by SINV are inadequately understood.
We studied the muscle pathology of SINV infection ex vivo by examining a unique muscle biopsy obtained from a patient with chronic myalgia and arthralgia 6 months after acute SINV infection and assessed potential genetic predisposing factors by determining the human leukocyte antigen (HLA) and complement factor C4 genes and proteins. In addition, we performed in vitro SINV infections of primary human myoblasts and myotubes.
In the muscle biopsy we found evidence of muscle regeneration due to previous necrotic lesions likely caused by earlier SINV infection. We showed that human myoblasts and myotubes were susceptible in vitro for SINV infection as the cells became immunoreactive for viral antigens and cytopathic effect was observed. The patient was homozygous for HLA-B*35 alleles and heterozygous for HLA-DRB1*01 and HLA-DRB1*03 alleles and had total deficiency of C4B protein.
This study provides new insights concerning pathological processes leading to chronic symptoms in SINV infection and demonstrates for the first time the susceptibility of human myogenic cells to SINV infection.
The Journal of Infectious Diseases 05/2012; 206(3):407-14. · 6.41 Impact Factor
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Sandra Martin-Latil,
Nina F Gnädig,
Adeline Mallet,
Marion Desdouits,
Florence Guivel-Benhassine,
Patricia Jeannin,
Marie-Christine Prevost,
Olivier Schwartz, Antoine Gessain,
Simona Ozden,
Pierre-Emmanuel Ceccaldi
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ABSTRACT: Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. In addition to blood transfusion and sexual transmission, HTLV-1 is transmitted mainly through prolonged breastfeeding, and such infection represents a major risk for the development of adult T-cell leukemia/lymphoma. Although HTLV-1-infected lymphocytes can be retrieved from maternal milk, the mechanisms of HTLV-1 transmission through the digestive tract remain unknown. In the present study, we assessed HTLV-1 transport across the epithelial barrier using an in vitro model. Our results show that the integrity of the epithelial barrier was maintained during coculture with HTLV-1-infected lymphocytes, because neither morphological nor functional alterations of the cell monolayer were observed. Enterocytes were not susceptible to HTLV-1 infection, but free infectious HTLV-1 virions could cross the epithelial barrier via a transcytosis mechanism. Such virions were able to infect productively human dendritic cells located beneath the epithelial barrier. Our data indicate that HTLV-1 crosses the tight epithelial barrier without disruption or infection of the epithelium to further infect target cells such as dendritic cells. The present study provides the first data pertaining to the mode of HTLV-1 transport across a tight epithelial barrier, as can occur during mother-to-child HTLV-1 transmission during breastfeeding.
Blood 05/2012; 120(3):572-80. · 9.90 Impact Factor
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Retrovirology 04/2012; 8:1-1. · 6.47 Impact Factor
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Capucine Picard,
Fethi Mellouli,
Renan Duprez,
Gaëlle Chédeville,
Bénédicte Neven,
Sylvie Fraitag,
Jean Delaunay,
Françoise Le Deist,
Alain Fischer,
Stéphane Blanche,
Christine Bodemer, Antoine Gessain,
Jean-Laurent Casanova,
Mohamed Bejaoui
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ABSTRACT: IntroductionKaposi’s sarcoma (KS) is rare in childhood. It may be favored by acquired immune deficiencies, but the predisposing factors to KS in other children are unclear.DiscussionKS has been reported in only two children and one adult with primary immunodeficiency. We report here a Tunisian child with a Wiskott-Aldrich syndrome who developed KS at the age of 14months.ConclusionThis observation expands the spectrum of primary immunodeficiencies associated with KS in childhood.
European Journal of Pediatrics 04/2012; 165(7):453-457. · 1.88 Impact Factor
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Linda Zane,
David Sibon,
Valérie Capraro,
Perrine Galia,
Maroun Karam,
Marie-Hélène Delfau-Larue,
Eric Gilson, Antoine Gessain,
Olivier Gout,
Olivier Hermine,
Franck Mortreux,
Eric Wattel
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ABSTRACT: Untransformed HTLV-1 positive CD4+ cells from infected individuals are selected for expressing tax and displaying morphological features consistent with telomere dysfunctions. We show that in resting HTLV-1 positive CD4+ cells cloned from patients, hTERT expression parallels tax expression and cell cycling. Upon activation, these cells dramatically augment tax expression, whereas their increase in telomerase activity is about 20 times lower than that of their uninfected counterpart. Activated HTLV-1 positive CD4+ but not uninfected CD4+ or CD8+ clones also repress the transcription of TRF1, TPP1, TANK1, POT1, DNA-PKc and Ku80. Both infected and uninfected lymphocytes from infected individuals shared common telomere gene deregulations toward a pattern consistent with premature senescence. ATLL cells displayed the highest telomerase activity (TA) whereas recovered a telomere gene transcriptome close to that of normal CD4+ cells. In conclusion HTLV-1-dependent telomere modulations seem involved in clonal expansion, immunosuppression, tumor initiation and progression.
International Journal of Cancer 04/2012; 131(4):821 - 833. · 5.44 Impact Factor
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ABSTRACT: Human T-cell leukemia virus (HTLV) indeterminate Western blot (WB) serological patterns are frequently observed in plasma/serum from persons living in intertropical areas. In the framework of ongoing projects on HTLV-1/2 and related viruses in Central Africa, we systematically analyzed plasma from villagers living in South Cameroon by WB. The group included 1,968 individuals (mean age, 44 years; age range, 5 to 90 years; 978 women/990 men), both Bantus (1,165) and Pygmies (803). Plasma samples were tested by WB analysis (MPD HTLV Blot 2.4) and interpreted according to the manufacturer's instructions. Only clear bands were considered in the analysis. Among the 1,968 plasma samples, 38 (1.93%) were HTLV-1, 13 (0.66%) were HTLV-2, and 6 (0.3%) were HTLV WB seropositive. Furthermore, 1,292 (65.65%) samples were WB sero-indeterminate, including 104 (5.28%) with an HTLV-1 Gag-indeterminate pattern (HGIP) and 68 (3.45%) with a peculiar yet unreported pattern exhibiting mostly a strong shifted GD21 and a p28. The other 619 (31.45%) samples were either WB negative or exhibited other patterns, mostly with unique p19 or p24 bands. DNA, extracted from peripheral blood buffy coat, was subjected to PCR using several primer pairs known to detect HTLV-1/2/3/4. Most DNAs from HTLV-1- and HTLV-seropositive individuals were PCR positive. In contrast, all the others, from persons with HTLV-2, HGIP, new WB, and other indeterminate patterns, were PCR negative. Epidemiological determinant analysis of the persons with this new peculiar WB pattern revealed that seroprevalence was independent from age, sex, or ethnicity, thus resembling the indeterminate profile HGIP rather than HTLV-1. Moreover, this new pattern persists over time.
Journal of clinical microbiology 03/2012; 50(5):1663-72. · 4.16 Impact Factor
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ABSTRACT: KSHV/HHV-8 is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma and most multicentric Castleman's disease cases. KSHV exhibits a high genetic variability comprising five genotypes (A-E). Few data are yet available concerning the situation of KSHV, its genetic variability and the associated diseases in Melanesia.
We performed a study on 626 natives Melanesians from New Caledonia and Vanikoro Island to evaluate KSHV seroprevalence and characterize molecularly the viral strains.
Plasma from 343 males and 283 females (age range: 15-86 years, mean age: 60) were tested for KSHV latent antibodies by an immunofluorescence assay (IFA) using BC-3 cells. DNAs extracted from peripheral blood buffy-coat of KSHV seropositive individuals were amplified to obtain a 737-bp fragment of the ORF-K1 gene. Phylogenetic analyses were then performed.
Among 626 samples, 148 were IFA positive (dilution≥1:80). The overall seroprevalence was 23.6% (25.2% in New Caledonia, 17.5% in Vanikoro). Fifteen (8 men and 7 women, mean age 69 years) out of 148 DNA samples were found PCR positive. All ORF-K1 sequences belonged to KSHV genotype D. A geographic clustering according to the island of origin of KSHV infected persons was clearly observed with sequences from New Caledonia clustering with most Vanuatu strains.
New Caledonia and Vanikoro are endemic for KSHV with a high diversity of genotype D variants. These strains were probably introduced into New Caledonia during multiple waves of migrations of Melanesian and Polynesian individuals that have colonized this archipelago.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 03/2012; 53(3):214-8. · 3.12 Impact Factor
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ABSTRACT: Homeostasis in the central nervous system (CNS) is maintained by active interfaces between the bloodstream and the brain parenchyma. The blood-brain barrier (BBB) constitutes a selective filter for exchange of water, solutes, nutrients, and controls toxic compounds or pathogens entry. Some parasites, bacteria, and viruses have however developed various CNS invasion strategies, and can bypass the brain barriers. Concerning viruses, these strategies include transport along neural pathways, transcytosis, infection of the brain endothelial cells, breaching of the BBB, and passage of infected-leukocytes. Moreover, neurotropic viruses can alter BBB functions, thus compromising CNS homeostasis. Retroviruses have been associated to human neurological diseases: HIV (human immunodeficiency virus 1) can induce HIV-associated dementia, and HTLV-1 (human T lymphotropic virus 1) is the etiological factor of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). The present review focuses on how the different retroviruses interact with this structure, bypass it and alter its functions.
Virulence 03/2012; 3(2):222-9. · 2.26 Impact Factor
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ABSTRACT: Infection with human herpesvirus 8 (HHV-8), the etiological agent of Kaposi's sarcoma, has been shown to display strong familial aggregation, in countries in which HHV-8 infection is endemic. We investigated 40 large families (608 subjects aged one to 88 years) living in an isolated area of Cameroon in which HHV-8 is highly endemic. We performed a two-step genetic analysis for HHV-8 infection status (HHV-8+/HHV-8- determined by immunofluorescence) consisting of an initial segregation analysis followed by a model-based genome-wide linkage analysis. Overall HHV-8 seroprevalence was 60%, increasing with age. Segregation analysis provided strong evidence for a recessive major gene conferring predisposition to HHV-8 infection. This gene is predicted to have a major effect during childhood, with almost all homozygous predisposed subjects (∼7% of the population) becoming infected by the age of 10. Linkage analysis was carried out on the 15 most informative families, corresponding to 205 genotyped subjects. A single region on chromosome 3p22 was significantly linked to HHV-8 infection (LOD score=3.83, P=2.0 × 10(-5)). This study provides the first evidence that HHV-8 infection in children in endemic areas has a strong genetic basis involving at least one recessive major locus on chromosome 3p22.
European journal of human genetics: EJHG 01/2012; 20(6):690-5. · 3.56 Impact Factor
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ABSTRACT: The human T-cell leukemia virus type 1 (HTLV-1), identified as the first human oncogenic retrovirus 30 years ago, is not an ubiquitous virus. HTLV-1 is present throughout the world, with clusters of high endemicity located often nearby areas where the virus is nearly absent. The main HTLV-1 highly endemic regions are the Southwestern part of Japan, sub-Saharan Africa and South America, the Caribbean area, and foci in Middle East and Australo-Melanesia. The origin of this puzzling geographical or rather ethnic repartition is probably linked to a founder effect in some groups with the persistence of a high viral transmission rate. Despite different socio-economic and cultural environments, the HTLV-1 prevalence increases gradually with age, especially among women in all highly endemic areas. The three modes of HTLV-1 transmission are mother to child, sexual transmission, and transmission with contaminated blood products. Twenty years ago, de Thé and Bomford estimated the total number of HTLV-1 carriers to be 10-20 millions people. At that time, large regions had not been investigated, few population-based studies were available and the assays used for HTLV-1 serology were not enough specific. Despite the fact that there is still a lot of data lacking in large areas of the world and that most of the HTLV-1 studies concern only blood donors, pregnant women, or different selected patients or high-risk groups, we shall try based on the most recent data, to revisit the world distribution and the estimates of the number of HTLV-1 infected persons. Our best estimates range from 5-10 millions HTLV-1 infected individuals. However, these results were based on only approximately 1.5 billion of individuals originating from known HTLV-1 endemic areas with reliable available epidemiological data. Correct estimates in other highly populated regions, such as China, India, the Maghreb, and East Africa, is currently not possible, thus, the current number of HTLV-1 carriers is very probably much higher.
Frontiers in microbiology. 01/2012; 3:388.
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Sandrine Leroy,
Despina Moshous,
Olivier Cassar,
Yves Reguerre,
Minji Byun,
Vincent Pedergnana,
Danielle Canioni, Antoine Gessain,
Eric Oksenhendler,
Claire Fieschi,
Nizar Mahlaoui,
Jean-Pierre Rivière,
Rose-Marie Herbigneaux,
Matthias Muszlak,
Jean-Pierre Arnaud,
Alain Fischer,
Capucine Picard,
Stéphane Blanche,
Sabine Plancoulaine,
Jean-Laurent Casanova
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ABSTRACT: Childhood multicentric Castleman disease (MCD) is a rare and unexplained lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected child, born to consanguineous Comorian parents, who displayed isolated MCD in the absence of any known immunodeficiency. We also systematically review the clinical features of the 32 children previously reported with isolated and unexplained MCD. The characteristics of this patient and the geographic areas of origin of most previous cases suggest that pediatric MCD is associated with HHV-8 infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood may result from inborn errors of immunity to HHV-8 infection.
PEDIATRICS 12/2011; 129(1):e199-203. · 4.47 Impact Factor
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ABSTRACT: Foamy viruses (FV) are nonpathogenic retroviruses that have cospeciated with primates for millions of years. FV can be transmitted through severe bites from monkeys to humans. Viral loads remain generally low in infected humans, and no secondary transmission has been reported. Very little is known about the ability of FV to trigger an innate immune response in human cells. A few previous reports suggested that FV do not induce type I interferon (IFN) in nonhematopoietic cells. Here, we examined how human hematopoietic cells sense FV particles and FV-infected cells. We show that peripheral blood mononuclear cells (PBMCs), plasmacytoid dendritic cells (pDCs), and the pDC-like cell line Gen2.2 detect FV, produce high levels of type I IFN, and express the IFN-stimulated gene MxA. Fewer than 20 FV-infected cells are sufficient to trigger an IFN response. Both prototypic and primary viruses stimulated IFN release. Donor cells expressing a replication-defective virus, carrying a mutated reverse transcriptase, induced IFN production by target cells as potently as wild-type virus. In contrast, an FV strain with env deleted, which does not produce viral particles, was inactive. IFN production was blocked by an inhibitor of endosomal acidification (bafilomycin A1) and by an endosomal Toll-like receptor (TLR) antagonist (A151). Silencing experiments in Gen2.2 further demonstrated that TLR7 is involved in FV recognition. Therefore, FV are potent inducers of type I IFN by pDCs and by PBMCs. This previously underestimated activation of the innate immune response may be involved in the control of viral replication in humans.
Journal of Virology 11/2011; 86(2):909-18. · 5.40 Impact Factor
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ABSTRACT: In order to characterize simian foamy retroviruses (SFVs) in wild-born nonhuman primates (NHPs) in Gabon and to investigate cross-species transmission to humans, we obtained 497 NHP samples, composed of 286 blood and 211 tissue (bush meat) samples. Anti-SFV antibodies were found in 31 of 286 plasma samples (10.5%). The integrase gene sequence was found in 38/497 samples, including both blood and tissue samples, with novel SFVs in several Cercopithecus species. Of the 78 humans, mostly hunters, who had been bitten or scratched by NHPs, 19 were SFV seropositive, with 15 cases confirmed by PCR. All but one were infected with ape SFV. We thus found novel SFV strains in NHPs in Gabon and high cross-species transmission of SFVs from gorilla bites.
Journal of Virology 11/2011; 86(2):1255-60. · 5.40 Impact Factor
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The Lancet 10/2011; 378(9799):1354. · 38.28 Impact Factor
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ABSTRACT: Human infection by simian foamy viruses (SFV) can be acquired by persons occupationally exposed to non-human primates (NHP) or in natural settings. This study aimed at getting better knowledge on SFV transmission dynamics, risk factors for such a zoonotic infection and, searching for intra-familial dissemination and the level of peripheral blood (pro)viral loads in infected individuals. We studied 1,321 people from the general adult population (mean age 49 yrs, 640 women and 681 men) and 198 individuals, mostly men, all of whom had encountered a NHP with a resulting bite or scratch. All of these, either Pygmies (436) or Bantus (1085) live in villages in South Cameroon. A specific SFV Western blot was used and two nested PCRs (polymerase, and LTR) were done on all the positive/borderline samples by serology. In the general population, 2/1,321 (0.2%) persons were found to be infected. In the second group, 37/198 (18.6%) persons were SFV positive. They were mostly infected by apes (37/39) FV (mainly gorilla). Infection by monkey FV was less frequent (2/39). The viral origin of the amplified sequences matched with the history reported by the hunters, most of which (83%) are aged 20 to 40 years and acquired the infection during the last twenty years. The (pro)viral load in 33 individuals infected by a gorilla FV was quite low (<1 to 145 copies per 10(5) cells) in the peripheral blood leucocytes. Of the 30 wives and 12 children from families of FV infected persons, only one woman was seropositive in WB without subsequent viral DNA amplification. We demonstrate a high level of recent transmission of SFVs to humans in natural settings specifically following severe gorilla bites during hunting activities. The virus was found to persist over several years, with low SFV loads in infected persons. Secondary transmission remains an open question.
PLoS Pathogens 10/2011; 7(10):e1002306. · 9.13 Impact Factor
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Matthew R Buckwalter,
Phan Thi Nga,
Meriadeg Ar Gouilh,
Laurence Fiette,
Jean-Francois Bureau,
Melissa E Laird,
Julian Buchrieser,
Simona Ozden,
Justine Cheval,
Marc Eloit,
Jean-Claude Manuguerra, Antoine Gessain,
Paul T Brey,
Arnaud Fontanet,
Matthew L Albert
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ABSTRACT: Theiler's murine encephalitis viruses (TMEV) are divided into two subgroups based on their neurovirulence. Persistent strains resemble Theiler's original viruses (referred to as the TO subgroup), which largely induce a subclinical polioencephalomyelitis during the acute phase of the disease and can persist in the spinal cord of susceptible animals, inducing a chronic demyelinating disease. In contrast, members of the neurovirulent subgroup cause an acute encephalitis characterized by the rapid onset of paralysis and death within days following intracranial inoculation. We report herein the characterization of a novel neurovirulent strain of TMEV, identified using pyrosequencing technology and referred to as NIHE. Complete coverage of the NIHE viral genome was obtained, and it shares <90% nucleotide sequence identity to known TMEV strains irrespective of subgroup, with the greatest sequence variability being observed in genes encoding the leader and capsid proteins. The histopathological analysis of infected brain and spinal cord demonstrate inflammatory lesions and neuronal necrosis during acute infection with no evidence of viral persistence or chronic disease. Intriguingly, genetic analysis indicates the putative expression of the L protein, considered a hallmark of strains within the persistent subgroup. Thus, the identification and characterization of a novel neurovirulent TMEV strain sharing features previously associated with both subgroups will lead to a deeper understanding of the evolution of TMEV strains and new insights into the determinants of neurovirulence.
Journal of Virology 07/2011; 85(14):6893-905. · 5.40 Impact Factor
