Open AccessParvovirus nonstructural protein 2 interacts with chromatin-regulating cellular proteins
Author(s) -
Salla Mattola,
Kari Salokas,
Vesa Aho,
Elina Mäntylä,
Sami Salminen,
Satu Hakanen,
Einari A. Niskanen,
Julija Svirskaitė,
Teemu O. Ihalainen,
Kari J. Airenne,
Minna U. Kaikkonen,
Colin R. Parrish,
Markku Varjosalo,
Maija VihinenRanta
Publication year - 2022
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1010353
Subject(s) - chromatin , biology , minute virus of mice , microbiology and biotechnology , parvovirus , chromatin remodeling , dna damage , viral replication , nuclear protein , dna replication , dna , genetics , virus , parvoviridae , gene , transcription factor
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.