The lung tissue score was obtained independently by two different investigators. The pathologic findings were graded according to a five-point semiquantitative severity-based scoring system: 0 = normal lung parenchyma; 1 = changes in 1-25%; 2 = 26-50%; 3 = 51-75%; and 4 = 76-100% of the examined tissue. Table 3 -Semiquantitative analysis of electron microscopy. In our current series, pulmonary ultrastructural analysis was important to obtain an understanding of the pathophysiology of this new disease. First, we demonstrated apoptosis and necrosis in the bronchiolar epithelium together with viral-like particles, thus suggesting the bronchiolar epithelium as the primary target of the virus infection. Second, we documented the submicroscopic pattern of a clastogenic DAD in S-OIV infection. Third, we found indirect evidence of virus infection in alveolar and bronchiolar epithelial cells represented by the TRS and CCC. These submicroscopic structures were demonstrated ultrastructurally in the lung tissue of all the patients and their presence suggests an inactivation of the virus by oseltamivir treatment or an altered innate immune response of these patients. They appeared mainly in respiratory cells and AECs and have previously been described in a variety of cell types. 28, 29 Usually, they occur in endothelial cells and lymphocytes from patients with autoimmune diseases and viral infections. 30 Patients with acquired immunodeficiency syndrome present TRS and CCC in these same cells. 31 The mechanism of TRS and CCC production in vivo is not definitely established. Nevertheless, clinical and experimental studies have shown that the presence of both structures in these diseases is directly associated with the increase of IFNa and IFNb but not with IFNc. 29 One theory to explain the nature and pathogenesis of TRS and CCC suggests that these structures are incomplete viral particles. 30 In our study, these viral-like particles were noted mainly in the respiratory epithelial cells, but not in the other cell types within the lung. These observations reinforce the hypothesis that the primary target cells for S-IOV infection are probably the bronchiolar epithelium. The atypical morphology of the bronchiolar and alveolar epithelial cells was probably related to viral cytopathic effects or reactive changes. In fact, the presence of multinucleated epithelial cells is not exclusive to S-IOV, and is seen in pneumonia caused by the family of Paramyxoviridae, including parainfluenza viruses, measles, mumps, respiratory syncytial virus and, perhaps, metapneumovirus. 31 Although multinucleated cells were seen in our cases, these probably reflect non-specific secondary changes.