Days of violent protests have seen Afghan security forces turn their weapons on US soldiers, rampaging demonstrators attack Western targets and Nato pull all its advisors out of government ministries.
"It has never been as bad as this and it could be a turning point" in the West's 10-year mission in the war-torn country, said Martine van Biglert of the Afghanistan Analysts' Network.
"There has been a very serious case of undermined trust and it really depends on whether it goes further downhill from here or the two sides get a chance to repair the damage," she told AFP.
At the heart of the escalating crisis is fear over Afghanistan's future when US-led Nato forces end combat operations in the war against Taliban insurgents in 2014 and hand security responsibility to the Afghan government.
"Fuses are very short, everybody is deeply concerned over the transition in 2014 and that has enhanced violent competition across the country," said Candace Rondeaux of the International Crisis Group.
"Relations have changed drastically. An accumulated sense of anxiety, anger and resentment has been building up for some time and it took a singular event -- the Quran burning -- to ignite a very big fire," she told AFP.
The US rushed to condemn the burning of Islam's holy book at the Bagram base north of Kabul, with President Barack Obama apologising to the Afghan people for what he said was a mistake and pledging the perpetrators would be punished.
But furious Afghans took to the streets across the country and tried to attack French, Norwegian, UN and US bases, shouting "Death to America" after the Taliban exhorted their countrymen to kill foreign troops to avenge the Quran burning.
At least 30 people died in five days of violent protests, including two US troops shot dead when an Afghan soldier turned his weapon on them as protesters approached their base in eastern Afghanistan.
Breaking point was reached when two senior American officers were shot and killed within the interior ministry in Kabul on Saturday, prompting the US commander to pull all advisors out of government ministries.
The Pentagon said the killings were "unacceptable" and called on Afghan authorities to better protect coalition forces and curtail raging violence.
The US, which leads a 130,000-strong military force fighting the Taliban-led insurgency, has advisors throughout the Kabul government.
The circumstances surrounding the shooting are still under investigation, but Taliban insurgents claimed the attack while a government source told AFP the two men were killed by a member of the Afghan police.
Cases of Afghan security forces turning on their Western allies have increased in recent years, with a leaked classified coalition report saying last month that they "reflect a rapidly growing systemic homicide threat".
Four French soldiers were gunned down by an Afghan colleague last month, prompting President Nicolas Sarkozy to announce an accelerated withdrawal of combat troops in 2013.
As pressure mounts on other Western governments to bring an early end to an unpopular campaign, fear grows among Afghans about their future.
"We expect violence to increase to the end of 2013 and after that we have the issue of transition, and uncertainty over the future is very high," said Afghan analyst Haroun Mir.
"There is a jockeying for power once the West leaves," he told AFP.
"People know that without the US -- and especially the financial assistance -- the Afghan government's survival will be difficult so people are already trying to show their allegiance to the Taliban and other insurgent groups."
President Hamid Karzai's government and Nato forces have appealed for calm and restraint, fearful that Taliban insurgents are trying to exploit the anti-American backlash.
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