Membrane and inclusion body targeting of lyssavirus matrix proteins

Pollin, Reiko; Granzow, Harald; Köllner, Bernd; Conzelmann, Karl‐Klaus; Finke, Stefan

doi:10.1111/cmi.12037

Cited by 17 publications

(15 citation statements)

References 31 publications

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“…The M protein, mainly involved in viral replication, can be differentially expressed in both of these samples, but this would require further investigation. 31 Although some reports show differences in clinical signs and evolution period in dogs presenting the furious and the paralytic form of the disease, 11 in our study this could not be stated once mice inoculated with variant 2 only presented the furious form. Brain tissue from mice inoculated with this strain showed high levels of viral replication, both in qRT-PCR and in FAT when compared to other viral strains studied, in agreement with a report that showed a high viral load in the brain of naturally infected dogs.…”

Section: Discussioncontrasting

confidence: 69%

Fluorescent antibody test, quantitative polymerase chain reaction pattern and clinical aspects of rabies virus strains isolated from main reservoirs in Brazil

Appolinário

Allendorf

Vicente

et al. 2015

The Brazilian Journal of Infectious Diseases

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Rabies virus (RABV) isolated from different mammals seems to have unique characteristics that influence the outcome of infection. RABV circulates in nature and is maintained by reservoirs that are responsible for the persistence of the disease for almost 4000 years. Considering the different pattern of pathogenicity of RABV strains in naturally and experimentally infected animals, the aim of this study was to analyze the characteristics of RABV variants isolated from the main Brazilian reservoirs, being related to a dog (variant 2), Desmodus rotundus (variant 3), crab eating fox, marmoset, and Myotis spp. Viral replication in brain tissue of experimentally infected mouse was evaluated by two laboratory techniques and the results were compared to clinical evolution from five RABV variants. The presence of the RABV was investigated in brain samples by fluorescent antibody test (FAT) and real time polymerase chain reaction (qRT-PCR) for quantification of rabies virus nucleoprotein gene (N gene). Virus replication is not correlated with clinical signs and evolution. The pattern of FAT is associated with RABV replication levels. Virus isolates from crab eating fox and marmoset had a longer evolution period and higher survival rate suggesting that the evolution period may contribute to the outcome. RABV virus variants had independent characteristics that determine the clinical evolution and survival of the infected mice.

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Section: Discussioncontrasting

confidence: 69%

Fluorescent antibody test, quantitative polymerase chain reaction pattern and clinical aspects of rabies virus strains isolated from main reservoirs in Brazil

Appolinário

Allendorf

Vicente

et al. 2015

The Brazilian Journal of Infectious Diseases

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“…These are characterized by the presence of N, P, and L proteins, and a variety of cellular proteins, including proviral heat shock proteins as well as antiviral innate immune sensors (Lahaye et al, 2009;Menager et al, 2009) and often are found associated with membranes and M protein (Pollin et al, 2013).…”

Section: Rabv Genomes and Gene Expressionmentioning

confidence: 99%

“…In rhabdoviruses, the M protein takes the key role in all steps during assembly, morphogenesis, and budding from the membrane (Black et al, 1993;Graham et al, 2008;Komarova et al, 2007). The RABV M is a small 202 aa basic protein which can form self-assemblies and associate with membranes, the cytoplasmic tail of the RABV G protein, and RNPs Pollin et al, 2013), and which therefore ties together the major virus components. Initially, the M protein is responsible for condensation of the RNP from the relaxed to the superhelical conformation which most likely takes place preferably at membranes harboring the G transmembrane proteins.…”

Section: Virus Morphogenesismentioning

confidence: 99%

G gene-deficient single-round rabies viruses for neuronal circuit analysis

Ghanem

Conzelmann

2016

Virus Research

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“…9A) would imply intracellular budding of RABV particles. Indeed, intracellular virus particle formation is known to occur within RABV-infected cells (45,46), and more recent data provided evidence for matrix protein-dependent accumulation of virus-like particles within the rough endoplasmic reticulum (rER) (30,47). Transport of virus particles within secretory Golgi vesicles, however, has not been observed so far.…”

Section: Discussionmentioning

confidence: 99%

Anterograde Glycoprotein-Dependent Transport of Newly Generated Rabies Virus in Dorsal Root Ganglion Neurons

Bauer

Nolden

Schröter

et al. 2014

J Virol

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Rabies virus (RABV) spread is widely accepted to occur only by retrograde axonal transport. However, examples of anterograde RABV spread in peripheral neurons such as dorsal root ganglion (DRG) neurons indicated a possible bidirectional transport by an uncharacterized mechanism. Here, we analyzed the axonal transport of fluorescence-labeled RABV in DRG neurons by livecell microscopy. Both entry-related retrograde transport of RABV after infection at axon endings and postreplicative transport of newly formed virus were visualized in compartmentalized DRG neuron cultures. Whereas entry-related transport at 1.5 m/s occurred only retrogradely, after 2 days of infection, multiple particles were observed in axons moving in both the anterograde and retrograde directions. The dynamics of postreplicative retrograde transport (1.6 m/s) were similar to those of entry-related retrograde transport. In contrast, anterograde particle transport at 3.4 m/s was faster, indicating active particle transport. Interestingly, RABV missing the glycoproteins did not move anterogradely within the axon. Thus, anterograde RABV particle transport depended on the RABV glycoprotein. Moreover, colocalization of green fluorescent protein (GFP)-labeled ribonucleoproteins (RNPs) and glycoprotein in distal axonal regions as well as cotransport of labeled RNPs with membrane-anchored mCherry reporter confirmed that either complete enveloped virus particles or vesicle associated RNPs were transported. Our data show that anterograde RABV movement in peripheral DRG neurons occurs by active motor protein-dependent transport. We propose two models for postreplicative long-distance transport in peripheral neurons: either transport of complete virus particles or cotransport of RNPs and G-containing vesicles through axons to release virus at distal sites of infected DRG neurons. IMPORTANCERabies virus retrograde axonal transport by dynein motors supports virus spread over long distances and lethal infection of the central nervous system. Though active rabies virus transport has been widely accepted to be unidirectional, evidence for anterograde spread in peripheral neurons supports the hypothesis that in some neurons RABV also enters the anterograde pathway by so-far unknown mechanisms. By live microscopy we visualized fast anterograde axonal transport of rabies virus. The velocities exceeded those of retrograde movements, suggesting that active, most likely kinesin-dependent transport machineries are involved. Dependency of anterograde transport on the expression of virus glycoprotein G and cotransport with vesicles further suggest that complete enveloped virus particles or cotransport of virus ribonucleoprotein and G-containing vesicles occurred. These data provide the first insight in the mechanism of anterograde rabies virus transport and substantially contribute to the understanding of RABV replication and spread of newly formed virus in peripheral neurons.

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Membrane and inclusion body targeting of lyssavirus matrix proteins

Cited by 17 publications

References 31 publications

Fluorescent antibody test, quantitative polymerase chain reaction pattern and clinical aspects of rabies virus strains isolated from main reservoirs in Brazil

Fluorescent antibody test, quantitative polymerase chain reaction pattern and clinical aspects of rabies virus strains isolated from main reservoirs in Brazil

G gene-deficient single-round rabies viruses for neuronal circuit analysis

Anterograde Glycoprotein-Dependent Transport of Newly Generated Rabies Virus in Dorsal Root Ganglion Neurons

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