In conclusion, in the present study we have identified a previously uncharacterized non-structural protein of BTV. The identification of this highly conserved protein opens the way to understand finer details of virus-host interaction and pathogenesis. In addition, the distinct nucleolar localization, in a virus that replicates exclusively in the cytoplasm will offer new avenues to understand the various roles played by these organelles in the biology of the cell. Interference of H-bonding and substituent effects in nitro- and hydroxy-substituted salicylaldehydes Two intramolecular interactions, i.e., (1) hydrogen bond and (2) substituent effect, were analyzed and compared. For this purpose, the geometry of 4- and 5-X-substituted salicylaldehyde derivatives (X = NO(2), H or OH) was optimized by means of B3LYP/6-311 + G(d,p) and MP2/aug-cc-pVDZ methods. The results obtained allowed us to show that substituents (NO(2) or OH) in the para or meta position with respect to either OH or CHO in H-bonded systems interact more strongly than in the case of di-substituted species: 4- and 3-nitrophenol or 4- and 3-hydroxybenzaldehyde by ∼31%. The substituent effect due to the intramolecular charge transfer from the para-counter substituent (NO(2)) to the proton-donating group (OH) is ∼35% greater than for the interaction of para-OH with the proton-accepting group (CHO). The total energy of H-bonding for salicylaldehyde, and its derivatives, is composed of two contributions: ∼80% from the energy of H-bond formation and ∼20% from the energy associated with reorganization of the electron structure of the systems in question. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-011-1044-1) contains supplementary material, which is available to authorized users. and (3) of the 4-hydroxy-salicylaldehyde (in red, see Table 2 ); in parenthesis SESE for para and meta di-substituted benzene derivatives (in green, Tables 3 and 4 ). (2) and (3) of the 5-nitro-salicylaldehyde (in red, see Table 2 ); in parenthesis SESE for para and meta di-substituted benzene derivatives (in green, Tables 3 and 4 ). (2) and (3) of the 4-nitrosalicylaldehyde (in red, see Table 2 ); in parenthesis SESE for para and meta di-substituted benzene derivatives (in green, Tables 3 and 4 ).  Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice BACKGROUND: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. However, no animal model has been developed for ARDS caused by infection with 2009 H1N1 virus. Here, we present a mouse model of ARDS induced by 2009 H1N1 virus. METHODOLOGY PRINCIPAL FINDINGS: Mice were inoculated with A/swine/Shandong/731/2009 (SD/09), which was a 2009 H1N1 influenza variant with a G222D mutation in the hemagglutinin. Clinical symptoms were recorded every day. Lung injury was assessed by lung water content and histopathological observation. Arterial blood gas, leukocyte count in the bronchial alveolar lavage fluid and blood, virus titers, and cytokine levels in the lung were measured at various times post-inoculation. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8–10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. CONCLUSIONS/SIGNIFICANCE: These results suggested that we successfully established an ARDS mouse model induced by a virulent 2009 H1N1 variant without previous adaptation, which may be of benefit for evaluating the pathogenesis or therapy of human ARDS caused by 2009 H1N1 virus. A novel influenza A (H1N1) virus of swine origin emerged among humans in Mexico during the spring of 2009 and rapidly spread worldwide [1] . The pandemic prompted the World Health Organization (WHO) to raise the alert level to the highest rating of six, the pandemic phase, within 2 months [2] . In August 2010, WHO officially declared that the disease was in the post-pandemic period [3] ; however, it is still circulating among humans, together with seasonal viruses. Although most influenza cases caused by 2009 H1N1 virus infection typically display mild upper respiratory tract syndrome, some cases progress to severe pneumonia and acute respiratory distress syndrome (ARDS) [4, 5] . Many studies have shown that ARDS caused by 2009 H1N1 virus results in 17.3-56% mortality [4, 6, 7, 8] , which was regarded as the major cause of death by 2009 H1N1 virus infection [9] . ARDS is the result of acute injury to lung tissue, commonly resulting from sepsis, trauma, and severe pulmonary infections [10] . Infectious factors, most of which are viruses, have become one of the most important causes of ARDS in humans [11, 12, 13] . Clinical cases and established animal models have revealed that the pathogenesis and pathological features of ARDS induced by different viral pathogens are distinct [14, 15] . However, knowledge of the pathogenesis of 2009 H1N1 virus, especially ARDS induced by 2009 H1N1 virus, is still limited and hinders therapeutic strategies. Therefore, it is necessary to evaluate the pathogenesis of ARDS caused by 2009 H1N1 virus infection in an appropriate animal model to assess potential therapies.