36 research outputs found
RĂŽle des leucocytes infectĂ©s du sperme dans la transmission muqueuse du VIH : modĂšle expĂ©rimental de lâinfection par le SIVmac251 de Macaca fascicularis
Human Immunodeficiency Virus (HIV) infection mostly spreads by the mucosal route: sexual transmission is the dominant mode of transmission, responsible for between 85% and 90% of cases of infection worldwide. These epidemiological data indicate that semen is one of the major sources of HIV-1 transmission. Semen, like other bodily secretions involved in HIV sexual transmission, contains the virus as two forms: cell-free viral particles and cell-associated virus, mostly in infected leukocytes. Although cell-to-cell HIV transmission has been extensively described as more efficient, rapid and resistant to host immune responses, very few studies have investigated the role in vivo of infected leukocytes in virus mucosal transmission. One such study has been recently conducted in our lab, and demonstrated that SIV-infected splenocytes are able to transmit infection to female macaques after vaginal exposure. However, all these studies used immune cells from peripheral blood or lymphoid tissues, such as spleen, and none have investigated the capacity of infected leukocytes in semen to transmit the infection in vivo. Indeed, nature, phenotype and infectivity of HIV associated with semen leukocytes may be different from that of HIV from other sources.Therefore, the objectives of this work are, first, to study of semen leukocytes and their dynamics during SIVmac251 infection in detail, then to investigate seminal factors that may influence semen infectiousness, and finally to test semen leukocyte infectivity in vitro and in vivo, using a model of mucosal exposure in cynomolgus macaques.Macaque semen contains all the target cells for HIV/SIV: CD4+ T cells, macrophages and dendritic cells in lower proportions. Semen CD4+ T cells and macrophages display an activation, differenciation and expression of migration markers profile which is typical of mucosal leucocytes. SIV infection induces significant changes in their phenotype and dynamics. Both cell types can be productively infected and are found in the semen at all stages of infection. These observations suggest that semen CD4+ T cells and macrophages may be able to transmit infection after mucosal exposure.If the role of semen infected leukocytes in HIV/SIV mucosal transmission is confirmed in vivo, this mechanism will be important to consider for further preventive strategies design, like microbicides.Aujourdâhui, plus de 80% des nouvelles infections par le virus de lâimmunodĂ©ficience humaine (VIH) se produisent au cours dâun rapport sexuel, avec une transmission du virus par voie muqueuse. Le sperme constitue donc une source majeure de virus Ă lâĂ©chelle mondiale. Le sperme dâhommes infectĂ©s par le VIH contient le virus sous deux formes : des particules virales libres et des cellules infectĂ©es, principalement des leucocytes.Plusieurs hypothĂšses ont Ă©tĂ© proposĂ©es afin dâexpliquer le passage du virus Ă travers la barriĂšre muqueuse, quâil sâagisse dâune muqueuse gĂ©nitale (cervico-vaginale, pĂ©nienne ou urĂ©trale) ou intestinale (muqueuse anale ou rectale). Toutefois, une grande majoritĂ© des Ă©tudes qui ont Ă©tĂ© menĂ©es jusquâĂ prĂ©sent se sont concentrĂ©es sur le rĂŽle des particules virales libres, et celui des cellules infectĂ©es demeure mal compris. Une Ă©tude menĂ©e dans notre laboratoire a montrĂ© que des leucocytes infectĂ©s par le virus de lâimmunodĂ©ficience simienne (VIS) sont capables de transmettre lâinfection aprĂšs inoculation vaginale.Le projet de cette thĂšse est dâĂ©tudier le rĂŽle des leucocytes infectĂ©s prĂ©sents dans le sperme de macaque dans la transmission muqueuse du VIS/VIH. Ainsi, trois axes dâĂ©tude principaux ont Ă©tĂ© dĂ©finis: 1) lâĂ©tude des leucocytes prĂ©sents dans le sperme de macaque cynomolgus, et de lâinfluence que peut avoir lâinfection par le VIS sur eux ; 2) lâidentification des cellules immunitaires infectĂ©es prĂ©sentes dans le sperme de macaque, et lâĂ©tude de leur dynamique au cours de lâinfection par le VIS. ; 3) lâĂ©tude du pouvoir infectieux des deux principales cellules cibles pour le VIS/VIH : les lymphocytes CD4+ (LT CD4+) et les macrophages, in vitro et in vivo, aprĂšs inoculation rectale et vaginale Ă des macaques cynomolgus.Le sperme de macaque contient toutes les cellules cibles du VIS/VIH : des lymphocytes T CD4+ (LTCD4+), des macrophages et des cellules dendritiques dans une moindre proportion). Les LTCD4+ et les macrophages du sperme prĂ©sentent un phĂ©notype dâactivation, de diffĂ©renciation et dâexpression de marqueurs de migration typique des leucocytes rĂ©sidant dans les tissus muqueux. Lâinfection par le VIS induit des changements significatifs dans leur phĂ©notype et leur dynamique. Ces deux types cellulaires peuvent ĂȘtre infectĂ©s de façon productive et sont prĂ©sents dans le sperme Ă tous les stades de lâinfection. Ces donnĂ©es suggĂšrent que les LTCD4+ et les macrophages du sperme seraient capables de transmettre lâinfection par voie muqueuse.Si le rĂŽle des leucocytes infectĂ©s du sperme est confirmĂ© in vivo, il sera important Ă lâavenir de prendre en compte ce mĂ©canisme de transmission dans le dĂ©veloppement de nouvelles stratĂ©gies prĂ©ventives de lâinfection par le VIH, notamment les microbicides
RÎle des leucocytes infectés du sperme dans la transmission muqueuse du VIH (ModÚle expérimental de l infection par le SIVmac251 de Macaca fascicularis)
Aujourd hui, plus de 80% des nouvelles infections par le virus de l immunodĂ©ficience humaine (VIH) se produisent au cours d un rapport sexuel, avec une transmission du virus par voie muqueuse. Le sperme constitue donc une source majeure de virus Ă l Ă©chelle mondiale. Le sperme d hommes infectĂ©s par le VIH contient le virus sous deux formes : des particules virales libres et des cellules infectĂ©es, principalement des leucocytes.Plusieurs hypothĂšses ont Ă©tĂ© proposĂ©es afin d expliquer le passage du virus Ă travers la barriĂšre muqueuse, qu il s agisse d une muqueuse gĂ©nitale (cervico-vaginale, pĂ©nienne ou urĂ©trale) ou intestinale (muqueuse anale ou rectale). Toutefois, une grande majoritĂ© des Ă©tudes qui ont Ă©tĂ© menĂ©es jusqu Ă prĂ©sent se sont concentrĂ©es sur le rĂŽle des particules virales libres, et celui des cellules infectĂ©es demeure mal compris. Une Ă©tude menĂ©e dans notre laboratoire a montrĂ© que des leucocytes infectĂ©s par le virus de l immunodĂ©ficience simienne (VIS) sont capables de transmettre l infection aprĂšs inoculation vaginale.Le projet de cette thĂšse est d Ă©tudier le rĂŽle des leucocytes infectĂ©s prĂ©sents dans le sperme de macaque dans la transmission muqueuse du VIS/VIH. Ainsi, trois axes d Ă©tude principaux ont Ă©tĂ© dĂ©finis: 1) l Ă©tude des leucocytes prĂ©sents dans le sperme de macaque cynomolgus, et de l influence que peut avoir l infection par le VIS sur eux ; 2) l identification des cellules immunitaires infectĂ©es prĂ©sentes dans le sperme de macaque, et l Ă©tude de leur dynamique au cours de l infection par le VIS. ; 3) l Ă©tude du pouvoir infectieux des deux principales cellules cibles pour le VIS/VIH : les lymphocytes CD4+ (LT CD4+) et les macrophages, in vitro et in vivo, aprĂšs inoculation rectale et vaginale Ă des macaques cynomolgus.Le sperme de macaque contient toutes les cellules cibles du VIS/VIH : des lymphocytes T CD4+ (LTCD4+), des macrophages et des cellules dendritiques dans une moindre proportion). Les LTCD4+ et les macrophages du sperme prĂ©sentent un phĂ©notype d activation, de diffĂ©renciation et d expression de marqueurs de migration typique des leucocytes rĂ©sidant dans les tissus muqueux. L infection par le VIS induit des changements significatifs dans leur phĂ©notype et leur dynamique. Ces deux types cellulaires peuvent ĂȘtre infectĂ©s de façon productive et sont prĂ©sents dans le sperme Ă tous les stades de l infection. Ces donnĂ©es suggĂšrent que les LTCD4+ et les macrophages du sperme seraient capables de transmettre l infection par voie muqueuse.Si le rĂŽle des leucocytes infectĂ©s du sperme est confirmĂ© in vivo, il sera important Ă l avenir de prendre en compte ce mĂ©canisme de transmission dans le dĂ©veloppement de nouvelles stratĂ©gies prĂ©ventives de l infection par le VIH, notamment les microbicides.Human Immunodeficiency Virus (HIV) infection mostly spreads by the mucosal route: sexual transmission is the dominant mode of transmission, responsible for between 85% and 90% of cases of infection worldwide. These epidemiological data indicate that semen is one of the major sources of HIV-1 transmission. Semen, like other bodily secretions involved in HIV sexual transmission, contains the virus as two forms: cell-free viral particles and cell-associated virus, mostly in infected leukocytes. Although cell-to-cell HIV transmission has been extensively described as more efficient, rapid and resistant to host immune responses, very few studies have investigated the role in vivo of infected leukocytes in virus mucosal transmission. One such study has been recently conducted in our lab, and demonstrated that SIV-infected splenocytes are able to transmit infection to female macaques after vaginal exposure. However, all these studies used immune cells from peripheral blood or lymphoid tissues, such as spleen, and none have investigated the capacity of infected leukocytes in semen to transmit the infection in vivo. Indeed, nature, phenotype and infectivity of HIV associated with semen leukocytes may be different from that of HIV from other sources.Therefore, the objectives of this work are, first, to study of semen leukocytes and their dynamics during SIVmac251 infection in detail, then to investigate seminal factors that may influence semen infectiousness, and finally to test semen leukocyte infectivity in vitro and in vivo, using a model of mucosal exposure in cynomolgus macaques.Macaque semen contains all the target cells for HIV/SIV: CD4+ T cells, macrophages and dendritic cells in lower proportions. Semen CD4+ T cells and macrophages display an activation, differenciation and expression of migration markers profile which is typical of mucosal leucocytes. SIV infection induces significant changes in their phenotype and dynamics. Both cell types can be productively infected and are found in the semen at all stages of infection. These observations suggest that semen CD4+ T cells and macrophages may be able to transmit infection after mucosal exposure.If the role of semen infected leukocytes in HIV/SIV mucosal transmission is confirmed in vivo, this mechanism will be important to consider for further preventive strategies design, like microbicides.PARIS11-SCD-Bib. Ă©lectronique (914719901) / SudocSudocFranceF
Health and economic impact of seasonal influenza mass vaccination strategies in European settings: A mathematical modelling and cost-effectiveness analysis
Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861572/Introduction: Despite seasonal influenza vaccination programmes in most countries targeting individuals aged â„ 65 (or â„ 55) years and high risk-groups, significant disease burden remains. We explored the impact and cost-effectiveness of 27 vaccination programmes targeting the elderly and/or children in eight European settings (n = 205.8 million).
Methods: We used an age-structured dynamic-transmission model to infer age- and (sub-)type-specific seasonal influenza virus infections calibrated to England, France, Ireland, Navarra, The Netherlands, Portugal, Scotland, and Spain between 2010/11 and 2017/18. The base-case vaccination scenario consisted of non-adjuvanted, non-high dose trivalent vaccines (TV) and no universal paediatric vaccination. We explored i) moving the elderly to "improved" (i.e., adjuvanted or high-dose) trivalent vaccines (iTV) or non-adjuvanted non-high-dose quadrivalent vaccines (QV); ii) adopting mass paediatric vaccination with TV or QV; and iii) combining the elderly and paediatric strategies. We estimated setting-specific costs and quality-adjusted life years (QALYs) gained from the healthcare perspective, and discounted QALYs at 3.0%.
Results: In the elderly, the estimated numbers of infection per 100,000 population are reduced by a median of 261.5 (range across settings: 154.4, 475.7) when moving the elderly to iTV and by 150.8 (77.6, 262.3) when moving them to QV. Through indirect protection, adopting mass paediatric programmes with 25% uptake achieves similar reductions in the elderly of 233.6 using TV (range: 58.9, 425.6) or 266.5 using QV (65.7, 477.9), with substantial health gains from averted infections across ages. At âŹ35,000/QALY gained, moving the elderly to iTV plus adopting mass paediatric QV programmes provides the highest mean net benefits and probabilities of being cost-effective in all settings and paediatric coverage levels.
Conclusion: Given the direct and indirect protection, and depending on the vaccine prices, model results support a combination of having moved the elderly to an improved vaccine and adopting universal paediatric vaccination programmes across the European settings.Highlights: Seasonal influenza vaccine programmes usually target at-risk and older individuals; We used an age-structured dynamic-transmission model for eight European settings; Older people benefit from adjuvanted or high-dose trivalent or quadrivalent vaccines; Adopting mass paediatric influenza vaccination is also likely to be cost-effective; Results rest on vaccine costs, willingness to vaccinate and unknown long-term effects.I-MOVE+ (Integrated Monitoring of Vaccines in Europe) project, received a grant from the European Commission Horizon 2020 research and innovation programme (grant agreement No 634446).info:eu-repo/semantics/publishedVersio
Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.
International audienceThe mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure
Modifications histologiques et répartition de la PrPres dans le tube digestif de Macaque rhésus infectés par l'agent infectieux de la variante de la maladie de Creutzfeldt-Jakob et de l'encéphalopathie spongiforme bovine
LYON1-BU Santé (693882101) / SudocTOULOUSE-EN Vétérinaire (315552301) / SudocSudocFranceF
Ancestral capture of syncytin-Car1, a fusogenic endogenous retroviral envelope gene involved in placentation and conserved in Carnivora
Syncytins are envelope protein genes of retroviral origin that have been captured for a function in placentation. Two such genes have already been identified in simians, two distinct, unrelated genes have been identified in Muridae, and a fifth gene has been identified in the rabbit. Here, we searched for similar genes in the Laurasiatheria clade, which diverged from Euarchontoglires--primates, rodents, and lagomorphs--shortly after mammalian radiation (100 Mya). In silico search for envelope protein genes with full-coding capacity within the dog and cat genomes identified several candidate genes, with one common to both species that displayed placenta-specific expression, which was revealed by RT-PCR analysis of a large panel of tissues. This gene belongs to a degenerate endogenous retroviral element, with precise proviral integration at a site common to dog and cat. Cloning of the gene for an ex vivo pseudotype assay showed fusogenicity on both dog and cat cells. In situ hybridization on placenta sections from both species showed specific expression at the level of the invasive fetal villi within the placental junctional zone, where trophoblast cells fuse into a syncytiotrophoblast layer to form the maternofetal interface. Finally, we show that the gene is conserved among a series of 26 Carnivora representatives, with evidence for purifying selection and conservation of fusogenic activity. The gene is not found in the Pholidota order and, therefore, it was captured before Carnivora radiation, between 60 and 85 Mya. This gene is the oldest syncytin gene identified to date, and it is the first in a new major clade of eutherian mammals
Impact of the lockdown on the burden of COVID-19 in outpatient care in France, spring 2020
International audienceBackground: To limit the spread of SARS-CoV-2 several countries implemented measures to reduce the number of contacts such as a national lockdown. We estimated the impact of the first lockdown on the burden of COVID-19 in the community in France.Methods: Physicians participating in the French Sentinelles network reported the number of patients with an acute respiratory infection (ARI) seen in consultation and performed nasopharyngeal swabs in a sample of these patients (first patient of the week). The swabs were tested by RT-PCR for the presence of SARS-CoV-2. Clinical and virological data were combined to estimate ARI incidence attributable to SARS-CoV-2 from 17 March to 10 May 2020.Results: The incidence of ARI attributable to COVID-19 decreased after the second week of the lockdown period from 142 (95%CI [101; 183]) to 41 (95%CI [21; 60]) per 100,000 population. A decrease was observed in all areas in metropolitan France. The youngest age groups (<15-years-old) were least affected with a cumulated incidence estimated to 14 per 100,000 population during the study period.Conclusions: The data collected in primary care suggests that the first lockdown implemented in France during spring 2020 significantly reduced the incidence of acute respiratory infections including COVID-19 in France and limited the geographic spread of SARS-CoV-2
Innate and Adaptive Anti-SIV Responses in Macaque Semen: Implications for Infectivity and Risk of Transmission
International audienc
Innate and Adaptive Anti-SIV Responses in Macaque Semen:Implications for Infectivity and Risk of Transmission
Impact of the Omicron variant on SARS-CoV-2 reinfections in France, March 2021 to February 2022
International audienceSince the first reports in summer 2020, SARS-CoV-2 reinfections have raised concerns about the immunogenicity of the virus, which will affect SARS-CoV-2 epidemiology and possibly the burden of COVID-19 on our societies in the future. This study provides data on the frequency and characteristics of possible reinfections, using the French national COVID-19 testing database. The Omicron variant had a large impact on the frequency of possible reinfections in France, which represented 3.8% of all confirmed COVID-19 cases since December 2021