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Oropouche (ORO) virus, a member of the Simbu serogroup, is one of the few human pathogens in the Orthobunyavirus genus in the family Bunyaviridae. Genetic analyses of ORO-like strains from Iquitos, Peru, identified a novel reassortant containing the S and L segments of ORO virus and the M segment of a novel Simbu serogroup virus. This new pathogen, which we named Iquitos (IQT) virus, was first isolated during 1999 from a febrile patient in Iquitos, an Amazonian city in Peru. Subsequently, the virus was identified as the cause of outbreaks of "Oropouche fever" during 2005 and 2006 in Iquitos. In addition to the identification of 17 isolates of IQT virus between 1999 and 2006, surveys for neutralizing antibody among Iquitos residents revealed prevalence rates of 14.9% for ORO virus and 15.4% for IQT virus. Limited studies indicate that prior infection with ORO virus does not seem to protect against disease caused with the IQT virus infection. Identification of a new Orthobunyavirus human pathogen in the Amazon region of Peru highlights the need for strengthening surveillance activities and laboratory capabilities, and investigating the emergence of new pathogens in tropical regions of South America. Author Summary: Oropouche (ORO) virus is one of the few human pathogens in the Orthobunyavirus genus in the family Bunyaviridae. Phylogenetic analyses of ORO-like strains isolated from febrile patients in Iquitos, Peru, identified a novel ORO reassortant virus, which we named Iquitos (IQT) virus based on the location of the isolation of the virus. This novel pathogen was first isolated during 1999 from a 13-year-old boy who had an illness that included symptoms of fever, headache, eye pain, body pain, arthralgias, diarrhea, and chills. Subsequently, the virus was identified as the cause of outbreaks of "Oropouche fever" during 2005 and 2006 in Iquitos. Limited serological studies indicate that prior infection with ORO virus does not seem to protect against disease caused with the IQT virus infection. In summary, we identified a new Orthobunyavirus human pathogen in the Amazon region of Peru; these results highlight the need for strengthening surveillance activities and investigating the emergence of new pathogens in tropical regions of South America. [ABSTRACT FROM AUTHOR]