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Asna1/TRC40 that mediates membrane insertion of tail-anchored proteins is required for efficient release of Herpes simplex virus 1 virions

Overview of attention for article published in Virology Journal, October 2016
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Title
Asna1/TRC40 that mediates membrane insertion of tail-anchored proteins is required for efficient release of Herpes simplex virus 1 virions
Published in
Virology Journal, October 2016
DOI 10.1186/s12985-016-0638-8
Pubmed ID
Authors

Melanie Ott, Débora Marques, Christina Funk, Susanne M. Bailer

Abstract

Herpes simplex virus type 1 (HSV1), a member of the alphaherpesvirinae, can cause recurrent facial lesions and encephalitis. Two membrane envelopment processes, one at the inner nuclear membrane and a second at cytoplasmic membranes are crucial for a productive viral infection. Depending on the subfamily, herpesviruses encode more than 11 different transmembrane proteins including members of the tail-anchored protein family. HSV1 encodes three tail-anchored proteins pUL34, pUL56 and pUS9 characterized by a single hydrophobic region positioned at their C-terminal end that needs to be released from the ribosome prior to posttranslational membrane insertion. Asna1/TRC40 is an ATPase that targets tail-anchored proteins to the endoplasmic reticulum in a receptor-dependent manner. Cell biological data point to a critical and general role of Asna1/TRC40 in tail-anchored protein biogenesis. With this study, we aimed to determine the importance of the tail-anchored insertion machinery for HSV1 infection. To determine protein-protein interactions, the yeast-two hybrid system was applied. Asna1/TRC40 was depleted using RNA interference. Transient transfection and virus infection experiments followed by indirect immunofluorescence analysis were applied to analyse the localization of viral proteins as well as the impact of Asna1/TRC40 depletion on virus infection. All HSV1 tail-anchored proteins specifically bound to Asna1/TRC40 but independently localized to their target membranes. While non-essential for cell viability, Asna1/TRC40 is required for efficient HSV1 replication. We show that early events of the replication cycle like virion entry and overall viral gene expression were unaffected by depletion of Asna1/TRC40. Furthermore, equal amounts of infectious virions were formed and remained cell-associated. This indicated that both nuclear egress of capsids that requires the essential tail-anchored protein pUL34, and secondary envelopment to form infectious virions were successfully completed. Despite large part of the virus life cycle proceeding normally, viral propagation was more than 10 fold reduced. We show that depletion of Asna1/TRC40 specifically affected a step late in infection during release of infectious virions to the extracellular milieu. Asna1/TRC40 is required at a late step of herpesviral infection for efficient release of mature virions to the extracellular milieu. This study reveals novel tools to decipher exocytosis of newly formed virions as well as hitherto unknown cellular targets for antiviral therapy.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 37%
Student > Bachelor 3 16%
Researcher 2 11%
Student > Master 2 11%
Student > Doctoral Student 1 5%
Other 2 11%
Unknown 2 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 32%
Medicine and Dentistry 4 21%
Biochemistry, Genetics and Molecular Biology 3 16%
Immunology and Microbiology 2 11%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Other 0 0%
Unknown 3 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 October 2016.
All research outputs
#14,036,882
of 15,918,484 outputs
Outputs from Virology Journal
#2,186
of 2,430 outputs
Outputs of similar age
#250,301
of 296,787 outputs
Outputs of similar age from Virology Journal
#179
of 183 outputs
Altmetric has tracked 15,918,484 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,430 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 183 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.