Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses

Pais-Correia, Ana-Monica; Sachse, Martin; Guadagnini, Stéphanie; Robbiati, Valentina; Lasserre, Rémi; Gessain, Antoine; Gout, Olivier; Alcover, Andrés; Thoulouze, María-Isabel

doi:10.1038/nm.2065

Cited by 283 publications

(353 citation statements)

References 48 publications

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“…The size of the cytoplasmic enveloped virions was estimated as 153-155 nm and 171-183 nm on two different particles. No structures compatible with extracellular virions or viral biofilm (Pais-Correia et al, 2010) were detected by SEM at the surface of EGFP-positive 3867K cells (not shown), a result in accordance with the absence of an EGFP signal at the cell surface after 3D reconstruction (Fig. 1e).…”

Section: Marek's Disease Virus (Mdv) (Species Gallid Herpesvirus 2)supporting

confidence: 79%

Marek's disease virus undergoes complete morphogenesis after reactivation in a T-lymphoblastoid cell line transformed by recombinant fluorescent marker virus

Denesvre¹,

Rémy²,

Trapp-Fragnet³

et al. 2016

Journal of General Virology

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T-lymphocytes are central targets of Marek's disease, a major chicken disease induced by the oncogenic alphaherpesvirus Marek's disease virus (MDV). T-lymphocyte infection is also associated with immunosuppression and virus latency. To decipher viral morphogenesis in T-lymphocytes, we used the recombinant vRB-1B 47EGFP marker virus to generate a new lymphoblastoid cell line, 3867K, that exhibited typical properties of other MDV-transformed chicken cell lines in term of cell markers, reactivation rate and infectivity. Examination of reactivating EGFP-positive 3867K cells by transmission electron microscopy revealed the presence of most types of herpesvirus particles inside the cells but no extracellular ones. Quantification of virion types indicated only 5 % cytoplasmic particles, with 0.5 % being mature. This study demonstrated that MDV morphogenesis is complete upon reactivation in T-lymphocytes, albeit with poor efficiency, with a defect in the exit of virions from the nucleus and secondary envelopment, as occurs in infected fibroblasts.

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Section: Marek's Disease Virus (Mdv) (Species Gallid Herpesvirus 2)supporting

confidence: 79%

Marek's disease virus undergoes complete morphogenesis after reactivation in a T-lymphoblastoid cell line transformed by recombinant fluorescent marker virus

Denesvre¹,

Rémy²,

Trapp-Fragnet³

et al. 2016

Journal of General Virology

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“…Engagement of these molecules is sufficient to trigger the reorientation of the MTOC in HTLV-1-infected T cells toward the cell-to-cell junction (26). Recent work also demonstrates that in both primary and cultured human lymphocytes, HTLV-1 viruses that bud from the cell surface can be entrapped within ECM and linker proteins reminiscent of bacterial biofilms (33). The findings of the current work are not in contradiction with prior data; rather, they demonstrate that HTLV-1 can also be transmitted by cellular conduits.…”

Section: Discussionmentioning

confidence: 99%

Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission

Prooyen

Gold

Andresen

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

143

212

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The human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/ HTLV-1-associated myelopathy. HTLV-1 is transmitted to T cells through the virological synapse and by extracellular viral assemblies. Here, we uncovered an additional mechanism of virus transmission that is regulated by the HTLV-1-encoded p8 protein. We found that the p8 protein, known to anergize T cells, is also able to increase T-cell contact through lymphocyte function-associated antigen-1 clustering. In addition, p8 augments the number and length of cellular conduits among T cells and is transferred to neighboring T cells through these conduits. p8, by establishing a T-cell network, enhances the envelope-dependent transmission of HTLV-1. Thus, the ability of p8 to simultaneously anergize and cluster T cells, together with its induction of cellular conduits, secures virus propagation while avoiding the host's immune surveillance. This work identifies p8 as a viral target for the development of therapeutic strategies that may limit the expansion of infected cells in HTLV-1 carriers and decrease HTLV-1-associated morbidity.human leukemia retrovirus | orf-I

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“…This is consistent with the requirement of cell-cell contact for viral transfer between lymphocytes. 41,42 Temperature dependence of the HTLV-1 passage and detection of viral particles within the Caco-2 cell cytoplasm by immunogold analysis at early steps (2 hours or less) strongly suggest transcytosis as an efficient mechanism of viral passage across a tight monolayer, which may occur in the first steps of HTLV-1 transmission. The existence of an HTLV-1 transcytosis mechanism across the enterocytes opens the question of the identification of HTLV-1 receptors that could be involved at the apical pole.…”

Section: Htlv-1 Passage Across Human Epithelial Barrier 577mentioning

confidence: 99%

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

Martin‐Latil

Gnädig

Mallet

et al. 2012

Blood

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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. IntroductionApproximately 5-20 million persons worldwide are infected by the human retrovirus human T-cell leukemia virus type 1 (HTLV-1), 1 and this virus is the causative agent of severe adult T-cell leukemia/lymphoma 2 and inflammatory syndromes such as tropical spastic paraparesis/HTLV-1-associated myelopathy, a slowly progressing neurodegenerative disease that occurs in 0.5%-3% of infected persons. 3 HTLV-1 is transmitted via sexual intercourse, by transfusion with contaminated blood, and from mother to child. The latter constitutes 15%-25% of overall transmission, so it is a major method of viral spread. 4,5 Although intrauterine or perinatal transmission during birth cannot be excluded, breastfeeding is the main pathway of HTLV-1 transmission in highly endemic areas such as intertropical Africa, the Caribbean, or regions of South America. 6,7 Milk-borne transmission is supported by the presence of high levels of infected lymphocytes in maternal milk, 10 5 -10 7 of these being transferred to the child at each feed, 8,9 in addition to infected macrophages and breast epithelial cells. Furthermore, leukocytes in the breast milk remain viable after ingestion for up to 4 hours because of the buffering capacity of breast milk and the low acidity of the neonatal child's stomach. 10,11 The risk of transmission increases with the time that children are breastfed, especially when this exceeds 6 months. In addition to the duration of breastfeeding, the mother's age, Ab titers directed against HTLV-1 antigens, proviral load in the PBMCs and milk, a...

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Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses

Cited by 283 publications

References 48 publications

Marek's disease virus undergoes complete morphogenesis after reactivation in a T-lymphoblastoid cell line transformed by recombinant fluorescent marker virus

Marek's disease virus undergoes complete morphogenesis after reactivation in a T-lymphoblastoid cell line transformed by recombinant fluorescent marker virus

Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

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