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The Cabinet minister risks inflaming tensions amid a bitter row over whether Greater Manchester should accept Tier 3 restrictions.
Michael Gove has accused Greater Manchester Mayor Andy Burnham of "posturing" and "political positioning" in refusing to accept strict new Covid-19 rules.
The government is currently at a stand-off with Mr Burnham over whether his region should be moved into the highest alert level of the new three-tier system for local coronavirus lockdowns.
Before agreeing to tougher Tier 3 restrictions, Mr Burnham has called for greater financial help for firms that would be affected by the move, which would see bars and pubs closed - and likely a number of other businesses.
Amid an increasingly bitter political row, Mr Gove, the Chancellor of the Duchy of Lancaster, risked further inflaming tensions between ministers and the Greater Manchester mayor.
Asked if the government would impose Tier 3 restrictions on Greater Manchester even without an agreement, Mr Gove told Sky News' Sophy Ridge On Sunday programme: "I want to reach an agreement with the political leadership in Greater Manchester.
"I want them to put aside, for a moment, some of the political positioning that they've indulged in. And I want them to work with us in order to ensure that we save lives and protect the NHS.
"An absence of action will mean more people will get infected, and as more people get infected that will place more pressure on the NHS.
"And the more people, sadly, in intensive care beds in the North West and in Manchester who are suffering from coronavirus, the fewer intensive care beds are there for people with other serious conditions.
"All of this is happening as we move closer to the winter and instead of press conferences and posturing, what we need is action to save people's lives."
Mr Burnam, a former Labour MP, later hit back at Mr Gove and refuted the suggestion he is "playing politics", as he pointed to the fact Greater Manchester was the first part of the country to accept localised COVID-19 restrictions at the end of July.
The mayor revealed he was due to hold a call with Sir Edward Lister, the prime minister's chief strategic adviser, on Sunday afternoon.
And he accused Boris Johnson of having exaggerated the severity of COVID-19 infections in Greater Manchester.
"It's a serious situation but I don't think it was the situation that was described by the prime minister on Friday evening," he told the BBC's Andrew Marr Show.
"I think it was an exaggeration of the position that we're in.
"Of course it's a matter of concern, and we watch the figures very closely indeed, but the figures have been falling in Manchester itself in the last few days, across Greater Manchester up slightly but certainly not doubling every nine days.
"So let's be careful here. I would certainly say this morning let's step back a bit from a war of words."
Mr Burnham has not ruled out a legal challenge against the government if Tier 3 restrictions are imposed without greater financial help for businsses.
"Anywhere could end up in Tier 3 this winter, in fact I would say places are likely to end up in Tier 3 this winter," he added.
"Therefore it's everyone's concern that we protect the lowest-paid in our communities and the self-employed who are left with nothing on the government's current deal."
The Greater Manchester mayor also criticised a letter from 20 conservative MPs, who have called on him to work with the government's regional approach to COVID-19 restrictions in the hope of avoiding another national lockdown.
"I'm not sure a sort of 'we're alright Jack' letter from a group of southern Conservative MPs is going to cut much ice here," Mr Burnham said.
Kate Green, Labour's shadow education secretary, told Sky News' Sophy Ridge that Greater Manchester should go into Tier 3 restrictions, but said her party's preference would be for a national "circuit breaker" lockdown.
"That will be more effective, more quickly, than this constant patchwork of checking in and then never being able to check out of local restrictions that people don't understand and where already we can see they are not proving effective," she said.
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