PML alternative splice products differentially regulate HAdV productive infection

Mai, J., Stubbe, M., Hofmann, S., Masser, S., Dobner, T., Boutell, C. , Groitl, P. and Schreiner, S. (2022) PML alternative splice products differentially regulate HAdV productive infection. Microbiology Spectrum, 10(4), e0078522. (doi: 10.1128/spectrum.00785-22) (PMID:35699431) (PMCID:PMC9431499)

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Abstract

Promyelocytic leukemia nuclear bodies (PML-NBs) were considered to maintain antiviral capacity, as these spherical complexes are antagonized by viruses. Actual work provides evidence, that PML-NB-associated factors might also be beneficial for distinct viral processes indicating why genomes and replication centers of nuclear replicating viruses are often found juxtaposed to PML-NBs. Several early HAdV proteins target PML-NBs, such as E4orf3 that promotes redistribution into track-like structures. PML-associated dependency factors that enhance viral gene expression, such as Sp100A remain in the nuclear tracks while restrictive factors, such as Daxx, are inhibited by either proteasomal degradation or relocalization to repress antiviral functions. Here, we did a comprehensive analysis of nuclear PML isoforms during HAdV infection. Our results show cell line specific differences as PML isoforms differentially regulate productive HAdV replication and progeny production. Here, we identified PML-II as a dependency factor that supports viral progeny production, while PML-III and PML-IV suppress viral replication. In contrast, we identified PML-I as a positive regulator and PML-V as a restrictive factor during HAdV infection. Solely PML-VI was shown to repress adenoviral progeny production in both model systems. We showed for the first time, that HAdV can reorganize PML-NBs that contain PML isoforms other then PML-II. Intriguingly, HAdV was not able to fully disrupt PML-NBs composed out of the PML isoforms that inhibit viral replication, while PML-NBs composed out of PML isoforms with beneficial influence on the virus formed tracks in all examined cells. In sum, our findings clearly illustrate the crucial role of PML-track formation in efficient viral replication.

Item Type:Articles
Keywords:Infectious Diseases, Cell Biology, Microbiology (medical), Genetics, General Immunology and Microbiology, Ecology, Physiology
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boutell, Dr Chris
Authors: Mai, J., Stubbe, M., Hofmann, S., Masser, S., Dobner, T., Boutell, C., Groitl, P., and Schreiner, S.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Microbiology Spectrum
Publisher:American Society for Microbiology
ISSN:2165-0497
ISSN (Online):2165-0497
Published Online:14 June 2022
Copyright Holders:Copyright © 2022 Mai et al
First Published:First published in Microbiology Spectrum 10(4): e0078522
Publisher Policy:Reproduced under a Creative Commons licence

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