BackgroundPerinatal infections with feline panleukopenia virus (FPV) have long been known to be associated with cerebellar hypoplasia in kittens due to productive infection of dividing neuroblasts. FPV, like other parvoviruses, requires dividing cells to replicate which explains the usual tropism of the virus for the digestive tract, lymphoid tissues and bone marrow in older animals.ResultsIn this study, the necropsy and histopathological analyses of a series of 28 cats which died from parvovirus infection in 2013 were performed. Infections were confirmed by real time PCR and immunohistochemistry in several organs. Strikingly, while none of these cats showed cerebellar atrophy or cerebellar positive immunostaining, some of them, including one adult, showed a bright positive immunostaining for viral antigens in cerebral neurons (diencephalon). Furthermore, infected neurons were negative by immunostaining for p27Kip1, a cell cycle regulatory protein, while neighboring, uninfected, neurons were positive, suggesting a possible re-entry of infected neurons into the mitotic cycle. Next-Generation Sequencing and PCR analyses showed that the virus infecting cat brains was FPV and presented a unique substitution in NS1 protein sequence. Given the role played by this protein in the control of cell cycle and apoptosis in other parvoviral species, it is tempting to hypothesize that a cause-to-effect between this NS1 mutation and the capacity of this FPV strain to infect neurons in adult cats might exist.ConclusionsThis study provides the first evidence of infection of cerebral neurons by feline panleukopenia virus in cats, including an adult. A possible re-entry into the cell cycle by infected neurons has been observed. A mutation in the NS1 protein sequence of the FPV strain involved could be related to its unusual cellular tropism. Further research is needed to clarify this point.

Endosomes have important roles in intracellular signal transduction as a sorting platform. Signaling cascades from TLR engagement to IRF3-dependent gene transcription rely on endosomes, yet the proteins that specifically recruit IRF3-activating molecules to them are poorly defined. We show that adaptor protein containing a pleckstrin-homology domain, a phosphotyrosine-binding domain, and a leucine zipper motif (APPL)1, an early endosomal protein, is required for both TRIF- and retinoic acid–inducible gene 1–dependent signaling cascades to induce IRF3 activation. APPL1, but not early endosome Ag 1, deficiency impairs IRF3 target gene expression upon engagement of both TLR3 and TLR4 pathways, as well as in H1N1-infected macrophages. The IRF3-phosphorylating kinases TBK1 and IKKε are recruited to APPL1 endosomes in LPS-stimulated macrophages. Interestingly, APPL1 undergoes proteasome-mediated degradation through ERK1/2 to turn off signaling. APPL1 degradation is blocked when signaling through the endosome is inhibited by chloroquine or dynasore. Therefore, APPL1 endosomes are critical for IRF3-dependent gene expression in response to some viral and bacterial infections in macrophages. Those signaling pathways involve the signal-induced degradation of APPL1 to prevent aberrant IRF3-dependent gene expression linked to immune diseases.

Influenza A virus remains a major public health problem. Mouse models have been widely used to study influenza infection in mammals. DBA/2J and C57BL/6J represent extremes in terms of susceptibility to influenza A infection among inbred laboratory mouse strains. Several studies focused specifically on the factors responsible for the susceptibility of DBA/2J or the resistance of C57BL/6J and resulted in impressive lists of candidate genes or factors over- or underexpressed in one of the strains. We adopted a different phenotypical approach to identify the critical steps of the infection process accounting for the differences between DBA/2J and C57BL/6J strains. We concluded that both a dysfunction of alveolar macrophages and an increased permissivity of respiratory cells rendered DBA/2J more susceptible to influenza infection.

N-acetylcysteine (NAC) is a mucolytic drug commonly used as an adjuvant therapy in patients with respiratory conditions associated with excessive mucus production. NAC also has anti-oxidant activities that proved useful in the management of oxidative stress. These anti-oxidant capacities of NAC are mostly indirect, via a pro-glutathione effect where NAC provides L-cysteine residues required for glutathione synthesis. This activity is thought to be the basis for the protective effect of NAC administration in influenza patients and in mouse models of the disease. NAC was shown to limit lung inflammation, damage associated with the virus, and viral growth, at least in vitro. However, the anti-viral activity was highly variable depending on the influenza A strain. The reasons for these inter-strain variations are still unknown, but might be related to the level of nuclear factor-κB activation required for the virus to achieve its infectious cycle.

During the 2016 spring, a local outbreak of severe dyspnea, seromucous nasal secretion, anorexia and loss of productive performance was identified in an intensive pig farm in southern Chile. Samples of diseased animals were submitted to the Diagnostic Laboratory of the Faculty of Veterinary Medicine, in Chillan, Chile, for pathological and histopathological study. Macroscopically, lungs appeared to be congested, edematous and "non-collapsed", which could be related to lesions compatible with interstitial pneumonia. Microscopic lesions showed a variable thickening of the septa, epithelial necrosis of the airways, diffuse inflammatory infiltration surrounding bronchial and bronchiolar areas, inflammatory exudate in the alveolar spaces with activate alveolar macrophages and fibrin. All lesions were compatible with Swine Influenza Virus (SIV) infection, and we successfully confirmed through SIV nucleoprotein immuno histochemistry staining of said samples, by utilizing a rapid and specific first-line diagnostic method that allows a rapid decision-making tool to control the spread of the virus. Additionally, the presence of the virus was confirmed by a serological field study.