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 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. Author summaryParvoviruses are small, nonenveloped DNA viruses, that besides being noteworthy pathogens in many animal species, including humans, are also being developed as vectors for gene and cancer therapy. Canine parvovirus is an autonomously replicating parvovirus that encodes two nonstructural proteins, NS1 and NS2. NS1 is required for viral DNA replication and packaging, as well as gene expression. However, very little is known about the function of NS2. Our studies indicate that NS2 serves a previously undefined important function in chromatin modification and DNA damage responses. Therefore, it appears that although both NS1 and NS2 are needed for a productive infection they play very different roles in the process.

Automated summary

The study found that CPV NS2 is involved in regulating chromatin modification and DNA damage response, a previously undefined function. While NS1 and NS2, which are associated with normal replication, play different roles in this process.