When does it make sense to send more inquiries asking about review progress to PLoS ONE?
PLOS One are pretty good at hassling editors to get a move on (I know, I am one) and if an editor doesn't move on a paper, they will reassign it to a new editor. So I don't think asking what's happening will help.

The usual reason for delays is reviewers. You ask someone to review. They don't reply. They are reminded. After two weeks, you give up and try to find a new reviewer. You invite them to review. After one week they agree. Two weeks later  a reminder is sent. A week after that another reminder is sent. A week after that you give up and invite a new reviewer. We are at two months, and we don't have a reviewer yet. 

The one thing that you might do to help is suggest reviewers. You might be aware of people who are working in the area that the editor may not know about (for example, because you have seen them present at a conference).