Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS.
BACKGROUND
Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans.


RESULTS
We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset.


CONCLUSIONS
The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease.
Nicholls
John M
JM
Department of Pathology, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China. nicholls@pathology.hku.hk
Butany
Jagdish
J
Poon
Leo L M
LL
Chan
Kwok H
KH
Beh
Swan Lip
SL
Poutanen
Susan
S
Peiris
J S Malik
JS
Wong
Maria
M
D000911:Antibodies, Monoclonal; D001344:Autopsy; D000086462:Coronavirus Nucleocapsid Proteins; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019590:Nucleocapsid Proteins / Q000032:analysis*; D011650:Pulmonary Alveoli / Q000821:virology; D020545:Respiratory Mucosa / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D045169:Severe Acute Respiratory Syndrome / Q000401:mortality / Q000503:physiopathology / Q000821:virology*; D013997:Time Factors; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D000086462:Coronavirus Nucleocapsid Proteins; D019590:Nucleocapsid Proteins