Article Figures & Data
Figures
- FIG. 1.
Kinetics and dose-response of SARS-CoV replication in the respiratory tract of mice. The graphs show the mean titers of virus detected on the indicated days in the lower respiratory tract (A) and upper respiratory tract (B) of four BALB/c mice per group following intranasal administration of the indicated doses of SARS-CoV. Error bars associated with each data point indicate standard errors, and the dotted line indicates the lower limit of detection of virus in 10% (wt/vol) (lungs) and 5% (wt/vol) (nasal turbinates) suspensions.
- FIG. 2.
Histopathology, immunohistochemistry, and in situ hybridization of mouse lung tissues harvested on day 2 following infection. (A) Focal and mild peribronchiolar mononuclear inflammatory infiltrate. Hematoxylin and eosin stain; magnification, ×158. (B) SARS-CoV antigens in multiple bronchiolar epithelial cells. Immunoalkaline phosphatase staining, naphthol-fast red substrate with light hematoxylin counterstain; original magnification, ×158. (C and D) SARS-CoV nucleic acids in multiple bronchiolar epithelial cells. Immunoalkaline phosphatase staining, naphthol-fast red substrate with light hematoxylin counterstain. Original magnification: C, ×100; D, ×250.
- FIG. 3.
Detection of viral nucleic acid in lung homogenates by RT-PCR. RNA extracted from serial 10-fold dilutions of lung homogenates obtained from mice that received passive transfers of immune or nonimmune serum was subjected to RT-PCR. For each dilution, the cycle number at which amplicons were detected is indicated. SARS-CoV nucleic acid was not detected at 45 cycles (dotted line) in lung homogenates from three mice (×, ▵, and □) that received passive transfers of immune serum but was detected in the virus stock (•) and also when virus was added exogenously to lung homogenates from mice that had received immune serum (⧫) or nonimmune serum (▪).
Tables
- TABLE 1.
Primary infection with SARS-CoV protects mice from subsequent challengea
Primary infection inoculum (TCID50) Challenge dose (TCID50) Neutralizing antibody titer Mean virus titer (log10 TCID50/g) ± SEb Lungs Nasal turbinates 105 105 1:25* 1.6 ± 0.13* ≤1.8 ± 0* 103 1:49* ≤1.5 ± 0c** ≤1.8 ± 0d* 0 (mock) 105 ≤1:8 6.5 ± 0.18 5.4 ± 0.30 103 ≤1:4 4.5 ± 1.02 4.5 ± 0.18 ↵a SARS-CoV challenge virus was administered intranasally 28 days following primary infection. Geometric mean neutralizing antibody titers in serum collected 28 days after primary infection were determined.
↵b *, P < 0.05 versus mock-infected control; **, P = 0.058 versus mock-infected control.
↵c Virus was not detected; this value represents the lower limit of detection of infectious virus in a 10% suspension.
↵d Virus was not detected; this value represents the lower limit of detection of infectious virus in a 5% suspension.
- TABLE 2.
Passive transfer of immune serum protects naïve mice from replication of challenge virus in the respiratory tract
Expt no. and dose of SARS-CoV (TCID50) Passively transferred seruma Neutralizing antibody titer in serumb Mean prechallenge neutralizing anti- body titer in re- cipient mice Virus replication in challenged mice Lungs Nasal turbinates No. of mice infected/no. tested Mean virus titerc ± SE No. of mice infected/no. tested Mean virus titer ± SE 1 (103) Immune 1:284 1:28 0/3 ≤1.5 ± 0d 2/3 3.2 ± 0.72 Nonimmune ≤1:4 ≤1:4 2/3 3.9 ± 1.21 2/3 2.4 ± 0.32 2 (104) Immune, undiluted 1:1,024 1:231 0/3 ≤1.8 ± 0e* 1/3 2.0 ± 0.17* Immune, 1:10 dilution 1:274 1:22 1/3 2.0 ± 0.17 2/3 3.3 ± 0.73 Nonimmune ≤1:4 ≤1:4 3/3 7.3 ± 0.14 3/3 5.6 ± 0.55 ↵a Serum (200 μl) pooled from immunized or uninfected mice was administered to recipient mice by intraperitoneal injection in experiment 1, and 500 μl of the indicated serum preparation was administered to mice in experiment 2.
↵b Titer of antibody that neutralized infectivity of 100 TCID50 of SARS-CoV.
↵c Virus titers are expressed as log10 TCID50 per gram of tissue. *, P < 0.05 versus nonimmune control.
↵d Virus not detected; this value represents the lower limit of detection of infectious virus in a 10% suspension.
↵e Virus not detected; this value represents the lower limit of detection of infectious virus in a 5% suspension.
