Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission

The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or ΔVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of ΔVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread

Poliovirus, pathogenesis of poliomyelitis, and apoptosis.

Poliovirus (PV) is the causal agent of paralytic poliomyelitis, an acute disease of the central nervous system (CNS) resulting in flaccid paralysis. The development of new animal and cell models has allowed the key steps of the pathogenesis of poliomyelitis to be investigated at the molecular level. In particular, it has been shown that PV-induced apoptosis is an important component of the tissue injury in the CNS of infected mice, which leads to paralysis. In this review the molecular biology of PV and the pathogenesis of poliomyelitis are briefly described, and then several models of PV-induced apoptosis are considered; the role of the cellular receptor of PV, CD155, in the modulation of apoptosis is also addressed

Poliovirus et apoptose

International audiencePoliovirus (PV) is the causal agent of paralytic poliomyelitis, an acute disease of the central nervous system (CNS). A killed and an oral live attenuated vaccine were both developed in the 1950s (Salk 1955; Sabin and Boulger 1973), and subsequent massive vaccination campaigns resulted in near total eradication of PV from most industrialized countries: currently, wild strains are endemic in only 10 countries. However, there are two current problems concerning PV: the occurrence, in rare cases, of poliomyelitis outbreaks due to oral-vaccine-derived PV strains (Nomoto and Arita 2002); and the development of a new neuro-muscular pathology, called the post-polio syndrome, in poliomyelitis survivors long after the acute disease (Dalakas 1995)

Poliovirus and apoptosis.

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

International audienceHuman 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

Real-time whole-body visualization of Chikungunya Virus infection and host interferon response in zebrafish.

International audienceChikungunya Virus (CHIKV), a re-emerging arbovirus that may cause severe disease, constitutes an important public health problem. Herein we describe a novel CHIKV infection model in zebrafish, where viral spread was live-imaged in the whole body up to cellular resolution. Infected cells emerged in various organs in one principal wave with a median appearance time of ∼14 hours post infection. Timing of infected cell death was organ dependent, leading to a shift of CHIKV localization towards the brain. As in mammals, CHIKV infection triggered a strong type-I interferon (IFN) response, critical for survival. IFN was mainly expressed by neutrophils and hepatocytes. Cell type specific ablation experiments further demonstrated that neutrophils play a crucial, unexpected role in CHIKV containment. Altogether, our results show that the zebrafish represents a novel valuable model to dynamically visualize replication, pathogenesis and host responses to a human virus