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Xavier de Lamballerie

Publications and source records attributed to Xavier de Lamballerie.

At least 19 recordsLinked to original sources

Unraveling the epidemiological and dispersal dynamics of the 2024-2025 chikungunya virus epidemic on Réunion Island.

Réunion Island experienced a massive chikungunya virus epidemic in 2024-2025, with >54,000 confirmed cases. This is the second major chikungunya epidemic on the island, following the first one that peaked 20 years ago. It has been asserted that this new outbreak finds its origin in a single introduction event into the island, offering an opportunity to exploit viral genomic data to understand the epidemiological and dispersal dynamics of the introduced transmission chain. We sequenced >3,000 viral genomes collected during the epidemic. Harnessing this genomic dataset, we used several phylogeographic and phylodynamic approaches to unravel the paths taken by the transmission chain and the external factors that might have impacted its dispersal and epidemiological dynamics on the island. Our analyses highlight a dispersal pattern in line with a gravity-model dynamic with viral transition events being more frequent from and toward more populated areas. Our analyses reveal that the transmission chain was overall spatially intermixed, with frequent exchanges among residential areas. In addition, we show that the temporal dynamic and intensity of the epidemic were associated with climatic variables, namely temperature and precipitation. Our results also show that in theory, the population immunity-resulting from this epidemic and the previous one (2005-2006)-could be sufficient to explain on its own the decrease in the transmission rate that led to the end of the epidemic. While a short-term resurgence cannot be excluded, the risk of a large-scale circulation of the virus in the human population appears therefore relatively limited in the upcoming seasons.

Reunion↗

Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy.

Here, we analyze the complete coding sequences of all recognized tick-borne flavivirus species, including Gadgets Gully, Royal Farm and Karshi virus, seabird-associated flaviviruses, Kadam virus and previously uncharacterized isolates of Kyasanur Forest disease virus and Omsk hemorrhagic fever virus. Significant taxonomic improvements are proposed, e.g. the identification of three major groups (mammalian, seabird and Kadam tick-borne flavivirus groups), the creation of a new species (Karshi virus) and the assignment of Tick-borne encephalitis and Louping ill viruses to a unique species (Tick-borne encephalitis virus) including four viral types (i.e. Western Tick-borne encephalitis virus, Eastern Tick-borne encephalitis virus, Turkish sheep Tick-borne encephalitis virus and Louping ill Tick-borne encephalitis virus). The analyses also suggest a complex relationship between viruses infecting birds and those infecting mammals. Ticks that feed on both categories of vertebrates may constitute the evolutionary bridge between the three distinct identified lineages.

Animals↗

Effective detection of highly divergent viral genomes in infected cell lines using a new subtraction strategy (primer extension enrichment reaction-PEER).

The development of new molecular approaches for identification or discovery of known and unknown pathogens is essential. The purpose of this study was to evaluate the utility of a new method designated primer extension enrichment reaction (PEER) in detecting viral genomes from highly divergent viral families (ssDNA, dsDNA, ssRNA, dsRNA) in infected cell lines. Findings indicate that the PEER methodology is a powerful tool since it permitted successful ex vivo detection of infectious agents from the Circoviridae, Herpesviridae, Paramyxoviridae, Picornaviridae and Reoviridae families. The great potential of PEER was further confirmed in tests using serial dilutions of West Nile virus (Flaviviridae) and in a "blind" test in which a member of the Poxviridae family was successfully identified. The technique was shown to be useful for identifying causative viral pathogens, following inoculation of susceptible cell lines with clinical biological samples.

Animals↗

Preliminary crystallographic characterization of an RNA helicase from Kunjin virus.

Kunjin virus is a member of the Flavivirus genus and is an Australian variant of West Nile virus. The C-terminal domain of the Kunjin virus NS3 protein displays helicase activity. The protein is thought to separate daughter and template RNA strands, assisting the initiation of replication by unwinding RNA secondary structure in the 3' nontranslated region. Expression, purification and preliminary crystallographic characterization of the NS3 helicase domain are reported. It is shown that Kunjin virus helicase may adopt a dimeric assembly in absence of nucleic acids, oligomerization being a means to provide the helicases with multiple nucleic acid-binding capability, facilitating translocation along the RNA strands. Kunjin virus NS3 helicase domain is an attractive model for studying the molecular mechanisms of flavivirus replication, while simultaneously providing a new basis for the rational development of anti-flaviviral compounds.

Amino Acid Sequence↗

Preliminary characterization of (nucleoside-2'-O-)-methyltransferase crystals from Meaban and Yokose flaviviruses.

Viral methyltranferases (MTase) are involved in the third step of the mRNA-capping process, transferring a methyl group from S-adenosyl-L-methionine (SAM) to the capped mRNA. MTases are classified into two groups: (guanine-N7)-methyltransferases (N7MTases), which add a methyl group onto the N7 atom of guanine, and (nucleoside-2'-O-)-methyltransferases (2'OMTases), which add a methyl group to a ribose hydroxyl. The MTases of two flaviviruses, Meaban and Yokose viruses, have been overexpressed, purified and crystallized in complex with SAM. Characterization of the crystals together with details of preliminary X-ray diffraction data collection (at 2.8 and 2.7 angstroms resolution, respectively) are reported here. The sequence homology relative to Dengue virus 2'OMTase and the structural conservation of specific residues in the putative active sites suggest that both enzymes belong to the 2'OMTase subgroup.

Crystallization↗

LoPPS: a long PCR product sequencing method for rapid characterisation of long amplicons.

Here, we propose an optimised protocol (LoPPS, long PCR product sequencing) which allows the fast, cost-attractive, and high-throughput sequencing of long PCR products. LoPPS constitutes an alternative to the primer-walking technology which is expensive and time consuming but remains the current standard procedure. It is based on the ultrasonic shearing, polishing, and cloning of PCR or RT-PCR products and is compatible with 96- or 384-well microplate systems in which bacterial growth, preparation of plasmid DNA, and sequencing can be automated. We present results obtained from 24 different RT-PCR products (2.5-4.8 kbp long) obtained from various RNA viruses and fully sequenced using LoPPS. The method proved to be robust and fast. It was successfully used on a low amount of DNA and allowed each target nucleotide position to be controlled twice or more, with a final cost which is one-third of that of primer-walking.

DNA↗

Phylogeny and evolution of old world arenaviruses.

The intention of this study was to investigate the genomics, phylogeny and evolution of the Old World arenaviruses based on sequence data representing the four viral genes. To achieve this aim, we sequenced the complete S and L RNA segments of Ippy virus (IPPYV), Mobala virus (MOBV) and Mopeia virus (MOPV). Full-length sequences of the NP, GPC, Z and L genes were used to reconstruct phylogenetic relationships and to compare resulting tree topologies. Each of the five Old World arenavirus species (namely Lassa virus [LASV], IPPYV, MOBV, MOPV and Lymphocytic choriomeningitis virus [LCMV]) are monophyletic; seven selected strains of LASV showed a similar topology regardless of the gene under analysis; IPPYV rooted the three other African arenaviruses; the four African arenaviruses are rooted by the ubiquitous LCMV; and the tree topologies of the three African arenaviruses other than LASV are identical regardless of the gene used for analysis. No evidence for significant evolutionary events such as intra- or intersegmental recombination was obtained.

Arenaviruses, Old World↗

Distribution and genetic analysis of TTV and TTMV major phylogenetic groups in French blood donors.

TTV and TTMV (recently assigned to the floating genus Anellovirus) infect human populations (including healthy individuals) at high prevalence (>80%). They display notably high levels of genetic diversity, but very little is known regarding the distribution of Anellovirus genetic groups in human populations. We analyzed the distribution of the major genetic groups of TTV and TTMV in healthy voluntary blood donors using group-independent and group-specific PCR amplifications systems, combined with sequence determination and phylogenetic analysis. Analysis of Anellovirus groups revealed a non-random pattern of group distribution with a predominant prevalence of TTV phylogenetic groups 1, 3, and 5, and of TTMV group 1. Multiple co-infections were observed. In addition, TTMV sequences exhibiting a high genetic divergence with reference sequences were identified. This study provided the first picture of the genetic distribution of the major phylogenetic groups of members of the genus Anellovirus in a cohort of French voluntary blood donors. Obtaining such data from a reference population comprising healthy individuals was an essential step that will allow the subsequent comparative analysis of cohorts including patients with well-characterized diseases, in order to identify any possible relationship between Anellovirus infection and human diseases.

Adolescent↗

Molecular epidemiology of hepatitis C virus subtype 3a in injecting drug users.

Hepatitis C virus subtype 3a (HCV-3a) originates from Asia and has spread widely among injecting drug users as well as other patient groups in industrialized countries. HCV subtype 3a infection remains highly prevalent and frequently transmitted in the population of intravenous drug users. The objective of this study was to understand better the mechanisms of the worldwide HCV-3a epidemics in drug users. Ninety-three sera from HCV-3a-infected IDUs from France, the United States, Brazil, Argentina, and Australia were studied. Phylogenetic analyses of the non-structural 5B region showed no specific clustering according to the continent of the patient's origin. Non-exclusive clusters of viral sequences from South America, Australia, and California were observed, but topologies were not supported by strong bootstrap values. The results suggest that HCV-3a has been transmitted from a common origin through a unique worldwide epidemic that rapidly spread among drug users. Regional transmission occurred in the recent past, leading to an embryonic genetic diversification of HCV-3a among local injecting drug user population.

Argentina↗

Liao ning virus, a new Chinese seadornavirus that replicates in transformed and embryonic mammalian cells.

Seadornaviruses are emerging arboviral pathogens from the south-east of Asia. The genus Seadornavirus contains two distinct species, Banna virus (BAV) isolated from humans with encephalitis and Kadipiro virus. BAV replicates within insect cells and mice but not in cultured mammalian cells. Here, the discovery of Liao ning virus (LNV), a new seadornavirus from the Aedes dorsalis mosquito, which was completely sequenced and was found to be related to BAV and Kadipiro virus, is reported. Two serotypes of LNV could be distinguished by a serum neutralization assay. According to amino acid identity with other seadornaviruses, and to criteria set by the ICTV for species delineation, LNV was identified as a member of a new species of virus. Its morphology was characterized by electron microscopy and found to be similar to that of BAV. LNV is the first reported seadornavirus that replicates in mammalian cells, leading to massive cytopathic effect in all transformed or embryonic cell lines tested. LNV- and BAV-infected mice producing a viraemia lasting for 5 days was followed by viral clearance. Mice infection generated virus quasi-species for LNV (the first reported observation for quasi-species in the family Reoviridae) but not for BAV. Challenge with BAV in mice immunized against BAV did not lead to productive infection. However, challenge with LNV in mice immunized against LNV was lethal with a new phase of viraemia and massive haemorrhage.

Aedes↗

Isolation of a new strain of the flavivirus cell fusing agent virus in a natural mosquito population from Puerto Rico.

The genus Flavivirus contains approximately 70 single-stranded, positive-sense RNA viruses that are mosquito-borne, tick-borne or have no known vector. Two discoveries support previous suggestions of the existence of a large number of unsampled flaviviruses: (i) a new flavivirus, Kamiti River virus, was recently isolated from Kenyan mosquitoes, and (ii) sequences with high similarity to those of flaviviruses have been found integrated into the genome of Aedes mosquitoes, suggesting a past infection with a virus (or viruses) that has yet to be discovered. These sequences were related most closely to a flavivirus that infects insects alone, cell fusing agent virus (CFAV). CFAV was originally isolated in the laboratory from an Aedes aegypti cell line. To date, this virus had not been found in the wild. In the present study, over 40 isolates of a novel strain of CFAV were discovered from mature mosquitoes sampled from the wild in Puerto Rico. The viral strain was present in a range of mosquito species, including Aedes aegypti, Aedes albopictus and Culex sp., from numerous locations across the island and, importantly, in mosquitoes of both sexes, suggesting vertical transmission. Here, results from viral screening, and cell culture and molecular identification of the infected mosquitoes are presented. Experimental-infection tests were also conducted by using the original CFAV strain and a highly efficient reverse-transcription mechanism has been documented, in which initiation of copying occurs at the 3' terminus of either the genomic RNA or the intermediate of replication, potentially elucidating the mechanism by which flaviviral sequences may have integrated into mosquito genomes.

Aedes↗

Micromonas pusilla reovirus: a new member of the family Reoviridae assigned to a novel proposed genus (Mimoreovirus).

Micromonas pusilla reovirus (MpRV) is an 11-segmented, double-stranded RNA virus isolated from the marine protist Micromonas pusilla. Sequence analysis (including conserved termini and presence of core motifs of reovirus polymerase), morphology and physicochemical properties confirmed the status of MpRV as a member of the family Reoviridae. Electron microscopy showed that intact virus particles are unusually larger (90-95 nm) than the known size of particles of viruses belonging to the family Reoviridae. Particles that were purified on caesium chloride gradients had a mean size of 75 nm (a size similar to the size of intact particles of members of the family Reoviridae), indicating that they lost outer-coat components. The subcore particles had a mean size of 50 nm and a smooth surface, indicating that MpRV belongs to the non-turreted Reoviridae. The maximum amino acid identity with other reovirus proteins was 21 %, which is compatible with values existing between distinct genera. Based on morphological and sequence findings, this virus should be classified as the representative of a novel genus within the family Reoviridae, designated Mimoreovirus (from Micromonas pusilla reovirus). The topology of the phylogenetic tree built with putative polymerase sequences of the family Reoviridae suggested that the branch of MpRV could be ancestral. Further analysis showed that segment 1 of MpRV was much longer (5792 bp) than any other reovirus segment and encoded a protein of 200 kDa (VP1). This protein exhibited significant similarities to O-glycosylated proteins, including viral envelope proteins, and is likely to represent the additional outer coat of MpRV.

Amino Acid Sequence↗

Ngoye virus: a novel evolutionary lineage within the genus Flavivirus.

By using degenerate primers deduced from conserved patterns in the flavivirus polymerase gene, a novel RNA virus was discovered in Rhipicephalus ticks sampled from members of the family Bovidae in Senegal. It was named Ngoye virus (NGOV) after the location from which it was isolated. Viral particles could be observed by electron microscopy, but isolation in vertebrate or invertebrate cell lines or by intracerebral infection of newborn mice remained unsuccessful. This is atypical of recognized arboviruses. The characterization of 4176 nt of the non-structural genes revealed that NGOV is a novel flavivirus species. It forms a distinct phylogenetic lineage related distantly to previously identified members of the genus Flavivirus. Analysis of genetic data suggested that the processing of the NGOV polyprotein and the organization of its replication complex are similar to those of flaviviruses. Together with other recent data, these findings suggest that a large number of viruses related distantly to 'classical' arthropod-borne flaviviruses remain to be discovered.

Animals↗

Analysis of the 5' noncoding region versus the NS5b region in genotyping hepatitis C virus isolates from blood donors in France.

The 5' noncoding region (5' NCR) of the hepatitis C virus (HCV) has become the standard for genotyping even though several reports show that its use can result in classification errors. The purpose of this study was to perform genotyping based on sequence analysis of the NS5b region in a set of 357 HCV strains isolated from blood donors in France in 2002 and 2003. Results were compared with those previously obtained using 5' NCR analysis, and HCV subtype distribution was reevaluated. Twenty-six of 120 strains (approximately 22%) initially identified as genotype 1b by 5' NCR region sequence analysis were reclassified as genotype 1a by NS5b region sequence analysis. Similarly, 14 of 23 strains (approximately 61%) initially identified as 2a/2c were reclassified as non-2a and non-2c subtypes, and 12 of 22 strains (approximately 45%) initially identified as 4c/4d subtypes were reclassified as non-4c and non-4d subtypes. Sequence analysis of the NS5b region also revealed 5 putative new subtype 2 variants and 2 putative new subtype 4 variants. Although these findings demonstrated full agreement between 5' NCR and NS5b sequence analysis with regard to type classification, genotyping based on phylogenetic analysis of the NS5b region is more accurate for subtype determination than genotyping based on analysis of the 5' NCR. Sequence analysis of the NS5b region is mandatory for epidemiologic studies.

5' Untranslated Regions↗

Novel chikungunya virus variant in travelers returning from Indian Ocean islands.

Chikungunya virus (CHIKV) emerged in Indian Ocean islands in 2005 and is causing an ongoing outbreak that involves >260,000 patients, including travelers returning home from these islands. We investigated cases in 4 patients returning from Mayotte and Reunion Islands with CHIKV infection and a nurse infected in metropolitan France after direct contact with the blood of a traveler. Four patients had tenosynovitis and pain at wrist pressure, and 1 had life-threatening manifestations. Four CHIKV strains were isolated, including 1 from the patient with the autochthonous case. The complete genomic sequence identified a new CHIKV variant emerging from the East/ central African evolutionary lineage. Aedes albopictus, the implicated vector of CHIKV in Indian Ocean islands, has dispersed worldwide in recent decades. High viral loads in patients returning from Indian Ocean islands to countries where Ae. albopictus is prevalent may be a source of epidemics.

Adult↗