Parvovirus nonstructural protein 2 interacts with chromatin-regulating cellular proteins

Autonomous parvoviruses encode at least two nonstructural proteins, NS1 and NS2. While NS1 is linked to important nuclear processes required for viral replication, much less is known about the role of NS2. Specifically, the function of canine parvovirus (CPV) NS2 has remained undefined. Here we have...

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Bibliographic Details
Published in:PLoS pathogens 2022-04, Vol.18 (4), p.e1010353-e1010353
Main Authors: Mattola, Salla, Salokas, Kari, Aho, Vesa, Mäntylä, Elina, Salminen, Sami, Hakanen, Satu, Niskanen, Einari A, Svirskaite, Julija, Ihalainen, Teemu O, Airenne, Kari J, Kaikkonen-Määttä, Minna, Parrish, Colin R, Varjosalo, Markku, Vihinen-Ranta, Maija
Format: Article
Language:English
Subjects:
Amino acids
Biology and Life Sciences
Biotin
Cell cycle
Cell Line
Cellular proteins
Chromatin
Chromatin remodeling
Damage
Deoxyribonucleic acid
DNA
DNA damage
Gene expression
Genetic aspects
Genomes
Health aspects
Herpes viruses
Humans
Infections
Kinases
Localization
Medicine and Health Sciences
Mutants
Mutation
Nonstructural proteins
NS2 protein
Parvoviridae Infections
Parvovirus - genetics
Parvoviruses
Proteins
Replication
Research and Analysis Methods
Viral infections
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
Virulence (Microbiology)
Virus Replication
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Summary:Autonomous parvoviruses encode at least two nonstructural proteins, NS1 and NS2. While NS1 is linked to important nuclear processes required for viral replication, much less is known about the role of NS2. Specifically, the function of canine parvovirus (CPV) NS2 has remained undefined. Here we have used proximity-dependent biotin identification (BioID) to screen for nuclear proteins that associate with CPV NS2. Many of these associations were seen both in noninfected and infected cells, however, the major type of interacting proteins shifted from nuclear envelope proteins to chromatin-associated proteins in infected cells. BioID interactions revealed a potential role for NS2 in DNA remodeling and damage response. Studies of mutant viral genomes with truncated forms of the NS2 protein suggested a change in host chromatin accessibility. Moreover, further studies with NS2 mutants indicated that NS2 performs functions that affect the quantity and distribution of proteins linked to DNA damage response. Notably, mutation in the splice donor site of the NS2 led to a preferred formation of small viral replication center foci instead of the large coalescent centers seen in wild-type infection. Collectively, our results provide insights into potential roles of CPV NS2 in controlling chromatin remodeling and DNA damage response during parvoviral replication.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1010353