Experimental infection with Sendai virus in mice

Summary Less than one plaque-forming unit (PFU) of Sendai virus was required to produce a serologically demonstrable infection when inoculated intranasally into mice of a specific pathogen-free colony showing no evidence of previous infection. No difference in susceptibility to serologically demonstrable infection and fatal disease was observed between male and female mice or between 4-week-old and 12-week-old mice.The distribution of virus and the antibody response were studied in 4-week-old and 12-week-old mice inoculated with 50 PFU of Sendai virus. Virus was recovered from the lungs and nasal washings from 24 hours after inoculation to at least 10 days later. Virus titers reached maximum levels at 4 to 6 days. No virus was recovered from the blood, intestines, kidneys and urine. Complement-fixing (CF), hemagglutination-inhibiting (HI) and neutralizing antibodies were demonstrable from the 8th day. Neutralizing antibody persisted at a higher level than did CF and HI antibodies.     

Experimental transmission of Sendai virus infection in mice

Summary A model was developed for experimental transmission of Sendai virus in mice. Infection could be transmitted by the airborne route as well as by direct contact. Mice were most infectious from the fifth to eighth day after onset of infection. Infectiousness was related to availability of virus in the respiratory tract. The frequency of transmitted infection was directly related to the number of infectious mice present. Some mice proved to transmit infection much more readily than others. Virus multiplication in contact mice appeared to be confined almost exclusively to the respiratory tract. Infected contacts were able to transmit infection to new contacts in eight succeeding generations.     

八肽胆囊收缩素对脂多糖诱导大鼠肺组织NF-κB活性增高的抑制作用

目的与方法：为探讨八肽胆囊收缩素（CCK-8）防治内毒素引起急性肺损伤的分子作用机理，用电泳迁移率变动分析技术（EMSA），观察CCK-8对脂多糖（LPS）诱导核转录因子κB（NF-κB）活性变化的影响，用光密度扫描电泳谱带峰面积积分值表示NF-κB活性，观察肺组织的病理学变化。结果：LPS入血可以明显引起大鼠肺组织的NF-κB活性1 639.92±198.63（P<0.01），显著高于对照组（593.56±89.34），此作用为预先静脉注入CCK-8部分逆转，NF-κB活性低至823.91±97.32（P<0.01），CCK-8可减轻LPS引起的肺组织病理学变化。结论：CCK-8对LPS激活肺组织NF-κB有抑制作用。     

Cell-mediated immunity to Sendai virus infection in mice.

The development of a cell-mediated immune response to Sendai virus infection in mice was examined by the use of a 51Cr release assay of cytotoxicity. A low level of "background cytotoxicity" to Sendai virus-infected L cells was found in the spleens of uninfected CBA mice. Spleen cells from Sendai-infected mice showed an elevated level of cytotoxicity against these target cells for a period of 5 weeks, commencing 4 days after infection of the mice. A more transient response was observed in the spleens of mice infected with a serologically distinct virus, the Kunz strain of influenza. This cross-reacting, cell-mediated immune response was intermediate between that observed in unsensitized and Sendai-sensitized spleen cells. The relevance of these cell-mediated immune responses to respiratory tract virus infections is discussed.     

Sendai virus infection up-regulates trypsin I and matrix metalloproteinase-9, triggering viral multiplication and matrix degradation in rat lungs and lung L2 cells

Summary. To elucidate the virus-host cell interaction, we analyzed quantitatively the expression of various cellular proteases and tumor necrosis factor-α (TNF-α) after Sendai virus infection in rat lungs and lung L2 cells. After infection, TNF-α mRNA levels increased rapidly to a peak on day one, and then trypsin I and matrix metalloproteinase (MMP)-9, but not MMP-2, were significantly up-regulated with a peak on day 2 in vivo. These up-regulations were confirmed in L2 cells. Up-regulation of proMMP-9 and its active convertase trypsin I seems to synergistically enhance virus multiplication and the destruction of lung matrix, resulting in the progression of pneumonia.     

Respiratory syncytial virus and pulmonary surfactant

Respiratory syncytial virus (RSV) infections peak in young infants and are associated with significant morbidity. The collectins surfactant protein-A (SP-A) and SP-D are pattern recognition molecules that belong to the innate immune system of the lungs, forming a first line of defense. On the one hand, SP-A and SP-D levels are reduced during RSV infection. This may critically influence the invasion of RSV and also the virus-induced cytokine patterns of the host. Both collectins enhance the in vivo elimination of RSV. Thus, interactions before the virus enters the epithelial cells may determine the course of the infection. On the other hand, during severe RSV infection in infants, the biophysical surfactant function is reduced and exogenous surfactant substitution may be a valid therapeutic option for selected infants. Thus, all components of the pulmonary surfactant system are involved during severe RSV infection. Especially the collectins SP-A and SP-D may play a pivotal role determining the short- and long-term course of RSV infections in early infancy.     

Replication of parainfluenza (Sendai) virus in isolated rat pulmonary type II alveolar epithelial cells.

The major objectives of this study were to determine whether alveolar type II epithelial cells isolated from rat lung and maintained in tissue culture would support productive replication of parainfluenza type 1 (Sendai) virus and to determine whether isolated type II cells from neonatal (5-day-old) rats that are more susceptible to viral-induced alveolar dysplasia supported viral replication to a greater extent than those from weanling (25-day-old) rats. Isolated and cultured type II cells from neonatal and weanling rats that were inoculated with Sendai virus supported productive replication as indicated by ultrastructural identification of budding virions and viral nucleocapsids in type II cells and by demonstration of rising titers of infectious virus from inoculated type II cell cultures. Alveolar macrophages from neonatal and weanling rats also supported viral replication, although infectious viral titers in macrophage cultures were lower than those from type II cell cultures. Only minor differences were detected between viral titers from neonatal and weanling type II epithelial cell cultures. Higher densities of viral nucleocapsids were observed in neonatal type II cells than in those from weanling rats. The results indicate that isolated type II alveolar epithelial cells support productive replication of parainfluenza virus and that type II cells are probably more efficient in supporting productive viral replication than are alveolar macrophages.     

Sendai virus infection in genetically resistant and susceptible mice.

The pathogenesis of Sendai virus infection in genetically resistant (C57Bl/6) and susceptible (DBA/2) nonimmune adult mice was investigated. Rising serum complement-fixation (CF) antibody titers were delayed in DBA/2 mice as compared with C57Bl/6 mice. C57Bl/6 mice developed descending desquamative endobronchiolitis, and DBA/2 mice developed descending proliferative endobronchiolitis and bronchogenic alveolitis. Peribronchiolar lymphoid cuffs that formed in C57Bl/6 mice were thicker and more densely populated than those of DBA/2 mice. Immunofluorescence demonstrated viral antigens confined to the epithelial lining of conducting airways in C57Bl/6 mice but extending to alveolar corner cells in DBA/2 mice. Studies with a transmission electron microscope confirmed that Type II pneumocytes were infected only in DBA/2 mice. IgG-containing cells selectively accumulated along the airways of both strains, but fewer were recruited by DBA/2 mice. These results suggest that genetic resistance to Sendai virus is expressed through the immune system.     

Genetics of natural resistance to Sendai virus infection in mice.

The genetics of resistance to a naturally occurring respiratory infection caused by Sendai virus was examined in F1, F2, and backcross progeny of resistant C57BL/6J and susceptible DBA/2J mice and in 25 recombinant inbred strains. An intranasal inoculum of 0.1 50% tissue culture infective dose (low dose) of Sendai virus caused 0% mortality in C57BL/6J and F1 mice and 73% mortality in DBA/2J mice. An inoculum of 1.0 50% tissue culture infective dose (high dose) caused 3, 0, and 89% mortality in C57BL/6J, F1, and DBA/2J mice, respectively. Low-dose infection caused 36% mortality in F1 X DBA/2J hybrids and 0% mortality in F2 hybrids. High-dose infection caused 29 and 32% mortality in F1 X DBA/2J and F2 hybrids, respectively. Resistance was not linked to H-2 haplotype, coat color, or sex. High-dose infection caused deaths in 12 recombinant inbred strains, and the strain distribution pattern was concordant with that of a chromosome 1 marker, Sas-1, in 20 of 25 strains (P less than 0.01). Resistance therefore behaved as a simple Mendelian dominant trait which presumptively mapped to chromosome 1.     

Activity and inhibition resistance of a phospholipase-resistant synthetic surfactant in rat lungs

This study investigates the activity and inhibition resistance in excised rat lungs of a novel synthetic surfactant containing the phospholipase-resistant diether phosphonolipid DEPN-8 plus 1.5% bovine surfactant protein (SP)-B/C compared to calf lung surfactant extract (CLSE). DEPN-8 + 1.5% SP-B/C surpassed CLSE in normalizing surfactant-deficient pressure-volume (P-V) deflation mechanics in lavaged excised lungs in the presence of phospholipase A(2) (PLA(2)) or C18:1 lyso-phosphatidylcholine (LPC). DEPN-8 + 1.5% SP-B/C had activity equal to CLSE in normalizing P-V mechanics in the absence of inhibitors or in the presence of serum albumin. These physiologic activity findings were directly consistent with surface activity measurements on the pulsating bubble surfactometer. In the absence of inhibitors, DEPN-8 + 1.5% SP-B/C and CLSE rapidly reached minimum surface tensions < 1 mN/m (0.5 and 2.5 mg surfactant phospholipid/ml). DEPN-8 + 1.5% SP-B/C maintained its high surface activity in the presence of PLA(2), while the surface activity of CLSE was significantly inhibited by exposure to this enzyme. DEPN-8 + 1.5% SP-B/C also had greater surface activity than CLSE in the presence of LPC, and the two surfactants had equivalent surface activity in the presence of albumin. DEPN-8 + 1.5% SP-B/C also had slightly greater surface activity than CLSE when exposed to peroxynitrite in pulsating bubble studies. These results support the potential of developing highly active and inhibition-resistant synthetic exogenous surfactants containing DEPN-8 + apoprotein/peptide constituents for use in treating direct pulmonary forms of clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS).     

Changes in bronchial response after Sendai virus infection in guinea pigs

Enhanced bronchial reactivity to inhaled histamine was observed in guinea pigs infected with Sendai virus with concomitant decrease of beta-adrenergic receptor density in the pulmonary parenchyma 2 to 3 weeks after the inoculation. Histologic examination of the bronchi showed shedding of epithelial cells with a marked infiltration of mononuclear cells. These observations suggest that damage of the bronchial epithelium and decreased density of beta-adrenergic receptor may be the causes of observed bronchial reactivity.     

Experimental inoculation of the adult rat testis with Sendai virus: effect on testicular morphology and leukocyte population

BACKGROUND: Surprisingly little is known about the interactions between viruses and the male uro-genital tract. These are important, as viral testicular orchitis, induced by mumps or human immunodeficiency virus (HIV) infection for example, can lead to sterility. Moreover, semen is an essential vector in the propagation of sexually transmissible viral diseases. Here, we studied the effects of testicular infection with Sendai virus, a virus related to mumps virus, on the cellular distribution of viral particles and on testicular morphology, with particular attention to the testicular leukocyte population. METHODS: At 5, 9, 11 or 24 h post-injection of Sendai virus through the scrotum, the testes were fixed for morphological and immunohistological studies. Localization of virus particles and numeration of leukocytes were performed using specific antibodies and morphological criteria. RESULTS: As early as 5 h post-injection, a rapid and massive infiltration of leukocytes was observed in the interstitial tissue. The peritubular cell layer and the most external part of the basal portion of the seminiferous tubules were altered. The virus was diffusely located within the interstitial tissue 9 h following the injection whereas, after 24 h, viral proteins were restricted to the cytoplasm of infiltrated leukocytes. The number of leukocytes increased with time post-injection. Thus, 24 h post-injection, CD3+ T-cell number was 3-fold higher, ED1+ monocyte number was 4-fold higher and polynuclear cell number was 600-fold higher than in the control testes (P<0.001 all observations). In contrast, the population of resident macrophages was unaffected by Sendai virus. CONCLUSIONS: Testicular viral infection causes inflammation including rapid recruitment of leukocytes. The experiments presented here provide a model for further studies on the etiopathology of viral orchitis, in particular that caused by mumps virus.