Pathology and virus dispersion in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus via different inoculation routes.
Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes SARS. The pathogenic mechanisms of SARS-CoV remain poorly understood. Six cynomolgus monkeys were inoculated with the HKU39849 isolate of SARS-CoV via four routes. After intranasal inoculation, the virus was isolated from respiratory swabs on days 2-7 postinoculation (p.i.) and virus genome was detected in intestinal tissues on day 7 p.i. Virus was not detected after intragastric inoculation. After intravenous inoculation, infectious virus was isolated from rectal swabs, and virus antigen was detected in intestinal cells on day 14 p.i. After intratracheal (i.t.) inoculation, virus antigen-positive alveolar cells and macrophages were found in lung and infectious virus was detected in lymphoid and intestinal tissues. The peribronchial lymph nodes showed evidence of an immune response. Lung tissue and/or fluid and/or the peribronchial lymph node of the intratracheally inoculated animals had high TNF-alpha, IL-8 and IL-12 levels. SARS lung lesions are only generated in monkeys by i.t. inoculation. The virus appears to spread into and perhaps via the intestinal and lymphatic systems. It has been suggested previously that viraemia may cause intestinal infections in SARS patients.
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan. nnagata@nih.go.jp
Noriyo
N
Nagata
Naoko
N
Iwata
Hideki
H
Hasegawa
Yuko
Y
Sato
Shigeru
S
Morikawa
Masayuki
M
Saijo
Shigeyuki
S
Itamura
Takehiko
T
Saito
Yasushi
Y
Ami
Takato
T
Odagiri
Masato
M
Tashiro
Tetsutaro
T
Sata
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D021821:Communicable Diseases, Emerging / Q000276:immunology / Q000635:transmission* / Q000821:virology; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D016679:Genome, Viral; D007267:Injections; D007275:Injections, Intravenous; D018664:Interleukin-12 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology*; D008221:Lymphoid Tissue / Q000821:virology; D008252:Macaca fascicularis; D008264:Macrophages / Q000821:virology; D016676:Macrophages, Alveolar / Q000821:virology; D008297:Male; D023421:Models, Animal; D012007:Rectum / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000472:pathogenicity*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000635:transmission*; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000956:Antigens, Viral; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12