title: Comparative pathogenesis of three human and zoonotic SARS-CoV strains in cynomolgus macaques.
abstract: The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. While there were significant differences in the number of host genes differentially regulated during the host responses between the three SARS-CoV strains, the top pathways and functions were similar and only apparent early during infection with the majority of genes associated with interferon signaling pathways. This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use.
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America. barry.rockx@utmb.edu
authors.forename: Barry
authors.initials: B
authors.lastname: Rockx
authors.forename: Friederike
authors.initials: F
authors.lastname: Feldmann
authors.forename: Douglas
authors.initials: D
authors.lastname: Brining
authors.forename: Don
authors.initials: D
authors.lastname: Gardner
authors.forename: Rachel
authors.initials: R
authors.lastname: LaCasse
authors.forename: Lisa
authors.initials: L
authors.lastname: Kercher
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rosenke
authors.forename: Kimmo
authors.initials: K
authors.lastname: Virtaneva
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.forename: John
authors.initials: J
authors.lastname: Mattoon
authors.forename: Michael
authors.initials: M
authors.lastname: Parnell
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000473:pathology* / Q000635:transmission; D014779:Virus Replication; D015047:Zoonoses
chemical_list: D016207:Cytokines