Spread and pathogenic characteristics of a G-deficient rabies virus recombinant: an in vitro and in vivo study

Etessami, Réza; Conzelmann, Karl‐Klaus; Fadai-Ghotbi, Babak; Natelson, Benjamin H.; Tsiang, H; Ceccaldi, Pierre‐Emmanuel

doi:10.1099/0022-1317-81-9-2147

Cited by 185 publications

(132 citation statements)

References 33 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, rabies viruses are transmitted from neuron to neuron in a transynaptic manner, and their G proteins, which were also shown here to bind hDlg, are absolutely required in this process (Etessami et al, 2000). This opens the exciting possibility that MAGUK proteins might represent essential cellular factors that assist the peculiar cell-to-cell transmission process of several unrelated viruses.…”

Section: Discussionmentioning

confidence: 96%

Human Dlg protein binds to the envelope glycoproteins of human T-cell leukemia virus type 1 and regulates envelope mediated cell-cell fusion in T lymphocytes

Blot

Delamarre

Perugi

et al. 2004

Journal of Cell Science

View full text Add to dashboard Cite

Human homologue of the Drosophila Dlg tumor suppressor (hDlg) is a widely expressed scaffold protein implicated in the organization of multi-protein complexes at cell adhesion sites such as the neuronal synapse. hDlg contains three PDZ domains that mediate its binding to the consensus motifs present at the C-termini of various cell surface proteins, thus inducing their clustering and/or stabilization at the plasma membrane. Using a yeast two-hybrid screen, we identified hDlg as a cellular binding partner of a viral membrane integral protein, the envelope glycoprotein (Env) of human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 is a human retrovirus that infects CD4+ T lymphocytes and is preferentially transmitted via direct contacts between infected and target cells, through a structure referred to as the virological synapse. Here, we demonstrate that hDlg interacts with a classical PDZ domain-binding motif present at the C-terminus of the cytoplasmic domain of HTLV-1 Env and conserved in the related HTLV-2 virus. We further document that, in HTLV-1 infected primary T cells, hDlg and Env are concentrated in restricted areas of the plasma membrane, enriched in molecules involved in T-cell contacts. The presence of Gag proteins responsible for viral assembly and budding in these areas indicated that they constitute platforms for viral assembly and transmission. Finally, a mutant virus unable to bind hDlg exhibited a decreased ability to trigger Env mediated cell fusion between T lymphocytes. We thus propose that hDlg stabilizes HTLV-1 envelope glycoproteins at the virological synapse formed between infected and target cells, hence assisting the cell-to-cell transmission of the virus.

show abstract

Section: Discussionmentioning

confidence: 96%

Human Dlg protein binds to the envelope glycoproteins of human T-cell leukemia virus type 1 and regulates envelope mediated cell-cell fusion in T lymphocytes

Blot

Delamarre

Perugi

et al. 2004

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…It is this unique property of the virus that makes it a useful transsynaptic neuronal tracer over many synapses (28,52), which is dependent on RVG (17).…”

mentioning

confidence: 99%

The Rabies Virus Glycoprotein Receptor p75 ^NTR Is Not Essential for Rabies Virus Infection

Tuffereau

Schmidt

Langevin

et al. 2007

J Virol

View full text Add to dashboard Cite

Rabies virus glycoprotein (RVG) is known to be the only factor that mediates rabies infection. The neurotrophin receptor (p75 NTR ), through its cysteine-rich domain 1, is a specific receptor for RVG and neutralizes virus infectivity, but its role in virus infection has remained obscure. We used adult mouse dorsal root ganglion (DRG) neurons as a model to study the role of p75 NTR in RV infection of primary neurons. We show that RV infects around 20% of DRG neurons, of which more than 80% are p75 NTR positive, have large diameters, and are capsaicin insensitive. Surprisingly, RV binding and infection are absent in about half of the p75 NTRexpressing DRG neurons which have small diameters and are often capsaicin sensitive. This indicates that p75 NTR is not sufficient to mediate RV interaction in sensory neurons. The rate and specificity of neural infection are unchanged in RV-infected p75 NTRExonIV؊/؊ mice that lack all extracellular receptor domains and in wild-type mice infected with two independent RV mutants that lack p75 NTR binding. Accordingly, the mortality rate is unchanged in the absence of RV-p75 NTR interaction. We conclude that although p75 NTR is a receptor for soluble RVG in transfected cells of heterologous expression systems, an RVG-p75 NTR interaction is not necessary for RV infection of primary neurons. This means that other receptors are required to mediate RV infection in vivo and in vitro.Rabies causes severe progressive encephalitis, myelitis, and paralysis and affects more than 50,000 people worldwide each year (59). After onset of symptoms, the infection progresses relentlessly, and there is only one documented case of a nonvaccinated human patient who survived the disease (56). Rabies virus (RV) belongs to the genus Lyssavirus in the family Rhabdoviridae and is a simple, enveloped, nonsegmented, negative-strand RNA virus that encodes only five proteins (44). The glycoprotein (G) is known to be the only protein component of the viral envelope that mediates viral entry into host cells (44).RV is highly neurotropic, and after inoculation it is retrogradely transported by peripheral neurons before being passed on to second and higher-order neurons without being taken up by glia. It is this unique property of the virus that makes it a useful transsynaptic neuronal tracer over many synapses (28,52), which is dependent on RVG (17).Although several receptors have been suggested to be responsible for RV infection, none has been conclusively identified. In previous studies we adopted an expression cloning strategy using a soluble form of RVG as a ligand. That work identified the neurotrophin receptor p75 NTR as a unique interacting receptor (50). We have also shown that the glycoprotein from another lyssavirus genotype (EBL2) is also able to interact with p75 NTR (51). p75 NTR belongs to the tumor necrosis factor receptor family (11,14) and is the common receptor for all known mature neurotrophins as well immature proneurotrophins (35). In addition, several other ligands implicated in the patholo...

show abstract

“…The rabies virus glycoprotein has been shown to play a key role in several steps of rabies pathogenesis-viral uptake from site of inoculation, axonal transport, and trans-synaptic spread in CNS, as well as the viral distribution in the nervous system [65][66][67]. The rabies viral glycoprotein (G) is critical for both neutralizing antibody production and the initiation of cell-mediated immune response.…”

Section: Viral Spread To the Cnsmentioning

confidence: 99%

Perspectives in Diagnosis and Treatment of Rabies Viral Encephalitis: Insights from Pathogenesis

et al. 2016

View full text Add to dashboard Cite

Rabies viral encephalitis, though one of the oldest recognized infectious disease of humans, remains an incurable, fatal encephalomyelitis, despite advances in understanding of its pathobiology. Advances in science have led us on the trail of the virus in the host, but the sanctuaries in which the virus remains hidden for its survival are unknown. Insights into host-pathogen interactions have facilitated evolving immunologic therapeutic strategies, though we are far from a cure. Most of the present-day knowledge has evolved from in vitro studies using fixed (attenuated) laboratory strains that may not be applicable in the clinical setting. Much remains to be unraveled about this elusive virus. This review attempts to re-examine the current advances in understanding of the pathobiology of the rabies virus that modulate the diagnosis, treatment, and prevention of this fatal disease.

show abstract

Spread and pathogenic characteristics of a G-deficient rabies virus recombinant: an in vitro and in vivo study

Cited by 185 publications

References 33 publications

Human Dlg protein binds to the envelope glycoproteins of human T-cell leukemia virus type 1 and regulates envelope mediated cell-cell fusion in T lymphocytes

Human Dlg protein binds to the envelope glycoproteins of human T-cell leukemia virus type 1 and regulates envelope mediated cell-cell fusion in T lymphocytes

The Rabies Virus Glycoprotein Receptor p75 ^NTR Is Not Essential for Rabies Virus Infection

Perspectives in Diagnosis and Treatment of Rabies Viral Encephalitis: Insights from Pathogenesis

Contact Info

Product

Resources

About

Spread and pathogenic characteristics of a G-deficient rabies virus recombinant: an in vitro and in vivo study

Cited by 185 publications

References 33 publications

Human Dlg protein binds to the envelope glycoproteins of human T-cell leukemia virus type 1 and regulates envelope mediated cell-cell fusion in T lymphocytes

Human Dlg protein binds to the envelope glycoproteins of human T-cell leukemia virus type 1 and regulates envelope mediated cell-cell fusion in T lymphocytes

The Rabies Virus Glycoprotein Receptor p75 NTR Is Not Essential for Rabies Virus Infection

Perspectives in Diagnosis and Treatment of Rabies Viral Encephalitis: Insights from Pathogenesis

Contact Info

Product

Resources

About

The Rabies Virus Glycoprotein Receptor p75 ^NTR Is Not Essential for Rabies Virus Infection