during his conflict with Vologases III, the latter succeeded by Vologases IV of Parthia (r. c. 147–191 AD) who ushered in a period of peace and stability. However, the Roman–Parthian War of 161–166 AD began when Vologases invaded Armenia and Syria, retaking Edessa. Roman emperor Marcus Aurelius (r. 161–180 AD) had co-ruler Lucius Verus (r. 161–169 AD) guard Syria while Marcus Statius Priscus invaded Armenia in 163 AD, followed by the invasion of Mesopotamia by Avidius Cassius in 164 AD. The Romans captured and burnt Seleucia and Ctesiphon to the ground, yet they were forced to retreat once the Roman soldiers contracted a deadly disease (possibly smallpox) that soon ravaged the Roman world. Although they withdrew, from this point forward the city of Dura-Europos remained in Roman hands. When Roman emperor Septimius Severus (r. 193–211 AD) invaded Mesopotamia in 197 AD during the reign of Vologases V of Parthia (r. c. 191–208 AD), the Romans once again marched down the Euphrates and captured Seleucia and Ctesiphon. After assuming the title Parthicus Maximus, he retreated in late 198 AD, failing as Trajan once did to capture Hatra during a siege. Around 212 AD, soon after Vologases VI of Parthia (r. c. 208–222 AD) took the throne, his brother Artabanus IV of Parthia (d. 224 AD) rebelled against him and gained control over a greater part of the empire. Meanwhile, the Roman emperor Caracalla (r. 211–217 AD) deposed the kings of Osroene and Armenia to make them Roman provinces once more. He marched into Mesopotamia under the pretext of marrying one of Artabanus' daughters, but—because the marriage was not allowed—made war on Parthia and conquered Arbil east of the Tigris river. Caracalla was assassinated the next year on the road to Carrhae by his soldiers. After this debacle, the Parthians made a settlement with Macrinus (r. 217–218) where the Romans paid Parthia over two-hundred million denarii with additional gifts. The Parthian Empire, weakened by internal strife and wars with Rome, was soon to be followed by the Sasanian Empire. Indeed, shortly afterward, Ardashir I, the local Iranian ruler of Persis (modern Fars Province, Iran) from Istakhr began subjugating the surrounding territories in defiance of Arsacid rule. He confronted Artabanus IV at the Battle of Hormozdgān on 28 April 224 AD, perhaps at a site near Isfahan, defeating him and establishing the Sasanian Empire. There is evidence, however, that suggests Vologases VI continued