Figure 5

(A) Experimental scheme. A total of 12 Chinese rhesus macaques were challenged i.n. with SARS-CoV_PUMC (1 × 10⁵ TCID₅₀). Four animals each were sacrificed at 2, 3, and 7 dpi. (B) SARS-CoV RNA detection by ISH in the lungs at 2, 3, and 7 dpi (original magnification, 200 ×). Viral RNA⁺ (TRITC) type I pneumocytes (FITC) was found at 2 dpi (n = 2) and 7 dpi (n = 1). (C) Viral RNA in the swabs and lung homogenates on 7 dpi. SARS-CoV RNA was detected using nested RT-PCR in swabs from 3 macaques (AD0516, AD0517, and AD0518) and lung homogenates from macaque AD0516. (D) Viral antigen and inflammatory infiltrates in the lungs at 7 dpi (200×). These sections were stained for SARS-CoV NP (red) and nucleus (blue) by IHC, showing NP signal in macrophage-like cells in AD0516 and AD0517 (red arrows), and type I pneumocytes in AD0518 (blue arrows), but substantial inflammatory infiltrates were only observed in AD0516 (green arrows). (E) Serum neutralizing activity. Serum neutralizing activity was detected in macaques AD0515 and AD0516 at 7 dpi. (F–I) Decreased wound-healing response in macaques with productive pulmonary viral infection and serum neutralizing activity (200×). These sections were double-immunostained for TGF-β (TRITC) and CD163 (FITC) or triple stained for CD206 (cyan), HAM56 (FITC), and CD163 (TRITC). The figure shows that wound-healing response took place within 2 dpi, with alternatively activated monocytes/macrophages (TGF-β⁺ and CD206⁺, white arrows) and IMMs (CD163⁺CD206^–, green arrows) coexisting in the lungs (F). After viral clearance, IMMs diminish at 3 dpi (G), and the homeostasis was restored at 7 dpi (AD0515) (H). When pulmonary viral infection persists, IMM (CD163⁺CD206^–, green arrows) infiltration and accumulation is enhanced, and wound-healing macrophages (CD206⁺) are reduced in macaques that have faster NAb response (AD0516) (I).