Primary infection of mice with high titer inoculum respiratory syncytial virus: characterization and response to antiviral therapy

2005 ◽  
Vol 83 (2) ◽  
pp. 198-213 ◽  
Author(s):  
Gordon Bolger ◽  
Nicole Lapeyre ◽  
Nathalie Dansereau ◽  
Lisette Lagacé ◽  
Gerald Berry ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Therapy ◽  
Virus Disease ◽  
High Titer ◽  
Lavage Fluid ◽  
Whole Body ◽  
Dependent Manner ◽  
Syncytial Virus ◽  
Dose Dependent

Intranasal infection of BALB/c mice with respiratory syncytial virus (RSV)-A2 (0.5 × 108– 2.0 × 108plaque-forming units, PFU) produced disease characterized by weight loss (2–3 g) and mortality (60%–100%) with the mean day of death ranging from 6–7 d after infection. The extent of RSV disease was inoculum titer-dependent and required a replication competent virus. Lung titers of virus peaked at 0.5-1 × 106PFU/g wet weight. Bronchoalveolar lavage fluid (BALF) levels of IL-1β, TNF-α, INF-γ IL-12, IL-6, MIP-1α, RANTES, and protein were elevated, whereas IL-2, IL-4, IL-5, IL-13, and IL-10 were unchanged. Histological assessment of lungs revealed marked inflammatory pathology characterized by bronchiolitis, vasculitis, and interstitial pneumonia. Whole-body plethysmography revealed significant disease-associated deficits of respiratory function. Therapy with ribavirin administered either by the intranasal, subcutaneous, or oral route significantly reduced disease in a dose-dependent manner. Delaying the initiation of therapy resulted in a loss of activity for ribavirin. Synagis®administered either intramuscularly as a single dose in prophylaxis or intranasally in prophylaxis, followed by therapy, also significantly reduced disease in a dose-dependent manner. Infection of mice with a high titer inoculum of RSV-A2 resulted in severe and fatal pulmonary disease that was responsive to treatment. This model may be useful to characterize the in vivo activity of experimental therapies for RSV infection.Key words: respiratory syncytial virus, disease, mortality, antiviral therapy.

scholarly journals The Antiinfective Effects of Velvet Antler of Formosan Sambar Deer (Cervus unicolor swinhoei) onStaphylococcus aureus-Infected Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Ting-Yeu Dai ◽  
Chih-Hua Wang ◽  
Kun-Nan Chen ◽  
I-Nung Huang ◽  
Wei-Sheng Hong ◽  
...  
Keyword(s):  
Lipoteichoic Acid ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
Protective Mechanisms ◽  
Velvet Antler ◽  
Sambar Deer ◽  
Dose Dependent ◽  
Cervus Unicolor

We assayed the effects of velvet antler (VA) of Formosan sambar deer (Cervus unicolor swinhoei) and its extracts on the anti-infective activity against pathogenicStaphylococcus aureus in vitroandin vivoin this study.In vitrodata indicated that the VA extracts stimulated the proliferation of resting splenocytes and macrophages in a dose-dependent manner up to the highest concentration used (150 μg mL−1). The production of proinflammatory cytokines (TNF-α, IL-6, IL-12) by lipoteichoic acid was significantly suppressed after being cocultured with the VA extracts in a dose-dependent manner. Animal test inS. aureus-infected mice demonstrated that the numbers of bacteria determined in the kidneys and peritoneal lavage fluid ofS. aureus-infected mice were significantly higher than those found in the same organs of mice pretreated with the VA samples. Moreover, the highly enhanced phagocytic activity of macrophages was further verified afterin vitrotreatment with the VA samples. The protective mechanisms of the VA samples might include an immune enhancer and an inflammatory cytokine suppressor.

scholarly journals Exacerbation of Influenza A Virus Disease Severity by Respiratory Syncytial Virus Co-Infection in a Mouse Model

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1630 ◽  
Author(s):  
Junu A. George ◽  
Shaikha H. AlShamsi ◽  
Maryam H. Alhammadi ◽  
Ahmed R. Alsuwaidi
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Immune Cell ◽  
Virus Disease ◽  
Viral Loads ◽  
Syncytial Virus

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are leading causes of childhood infections. RSV and influenza are competitive in vitro. In this study, the in vivo effects of RSV and IAV co-infection were investigated. Mice were intranasally inoculated with RSV, with IAV, or with both viruses (RSV+IAV and IAV+RSV) administered sequentially, 24 h apart. On days 3 and 7 post-infection, lung tissues were processed for viral loads and immune cell populations. Lung functions were also evaluated. Mortality was observed only in the IAV+RSV group (50% of mice did not survive beyond 7 days). On day 3, the viral loads in single-infected and co-infected mice were not significantly different. However, on day 7, the IAV titer was much higher in the IAV+RSV group, and the RSV viral load was reduced. CD4 T cells were reduced in all groups on day 7 except in single-infected mice. CD8 T cells were higher in all experimental groups except the RSV-alone group. Increased airway resistance and reduced thoracic compliance were demonstrated in both co-infected groups. This model indicates that, among all the infection types we studied, infection with IAV followed by RSV is associated with the highest IAV viral loads and the most morbidity and mortality.

scholarly journals Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats

2008 ◽  
Vol 89 (1) ◽  
pp. 261-270 ◽  
Author(s):  
Lioubov M. Pletneva ◽  
Otto Haller ◽  
David D. Porter ◽  
Gregory A. Prince ◽  
Jorge C. G. Blanco
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Virus Replication ◽  
Surrogate Marker ◽  
Type I Interferons ◽  
Type I ◽  
Dependent Manner ◽  
Type I Ifn ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis in young children. In general, RSV is considered to be a poor inducer of type I (alpha/beta) interferons (IFNs). Measurement of active type I IFN production during infection in vivo is demanding, as multiple IFN subtypes with overlapping activities are produced. In contrast, Mx gene expression, which is tightly regulated by type I IFN expression, is easily determined. This study therefore measured Mx expression as a reliable surrogate marker of type I IFN activity during RSV infection in vivo in a cotton rat model. It was shown that expression of Mx genes was dramatically augmented in the lungs of infected animals in a dose- and virus strain-dependent manner. The expression of Mx genes in the lungs was paralleled by their induction in the nose and spleen, although in spleen no simultaneous virus gene expression was detected. Reinfection of RSV-immune animals leads to abortive virus replication in the lungs. Thus, type I IFN and Mx gene expression was triggered in reinfected animals, even though virus could not be isolated from their lungs. Furthermore, it was demonstrated that immunity to RSV wanes with time. Virus replication and Mx gene expression became more prominent with increasing intervals between primary infection and reinfection. These results highlight the role of type I IFN in modulation of the immune response to RSV.

Erratum: Primary infection of mice with high titer inoculum respiratory syncytial virus: characterization and response to antiviral therapy

2005 ◽  
Vol 83 (3) ◽  
pp. 319-319
Author(s):  
Gordon Bolger ◽  
Nicole Lapeyre ◽  
Nathalie Dansereau ◽  
Lisette Lagacé ◽  
Gerald Berry ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antiviral Therapy ◽  
Primary Infection ◽  
High Titer ◽  
Syncytial Virus

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

scholarly journals Burden of Respiratory Syncytial Virus Disease and Mortality Risk Factors in Argentina

2019 ◽  
Vol 38 (6) ◽  
pp. 589-594 ◽  
Author(s):  
Angela Gentile ◽  
María Florencia Lucion ◽  
María del Valle Juarez ◽  
María Soledad Areso ◽  
Julia Bakir ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Syncytial Virus ◽  
Mortality Risk ◽  
Virus Disease ◽  
Respiratory Syncytial Virus Disease ◽  
Syncytial Virus

scholarly journals Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

2021 ◽  
Author(s):  
Li-Nan Wang ◽  
Xiang-Lei Peng ◽  
Min Xu ◽  
Yuan-Bo Zheng ◽  
Yue-Ying Jiao ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Gene Deletion ◽  
Human Respiratory Syncytial Virus ◽  
Temperature Sensitive ◽  
T7 Promoter ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractHuman respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5′ to 3′) a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed  temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.

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