Respiratory Syncytial Virus Load Research Articles

Respiratory syncytial virus induces pneumonia, cytokine response, airway obstruction, and chronic inflammatory infiltrates associated with long-term airway hyperresponsiveness in mice.

Respiratory syncytial virus (RSV) infection is associated with acute morbidity (e.g., pneumonia and airway obstruction [AO]) and long-term complications (e.g., airway hyperresponsiveness [AHR]). We present a comprehensive evaluation of the acute and chronic phases of RSV respiratory tract infection, using a mouse model. BALB/c mice were inoculated with RSV and monitored for 154 days. RSV loads and cytokines were measured in bronchoalveolar lavage (BAL) samples. Pneumonia severity was assessed using a standard histopathologic score, and pulmonary function was determined by plethysmography. RSV-infected mice exhibited viral replication that peaked on day 4-5 and became undetectable by day 7. These mice developed acute pneumonia (peak days, 4-5) and chronic pulmonary inflammatory infiltrates that lasted up to 154 days after inoculation. BAL concentrations of tumor necrosis factor- alpha, interleukin (IL)-6, interferon- gamma, IL-4, IL-10, KC (an IL-8 homologue), MIG (CXCL9), RANTES, macrophage inflammatory protein-1 alpha, and eotaxin were significantly higher in RSV-infected mice than in control mice. RSV-infected mice developed acute AO during the first week of infection that persisted for 42 days. RSV-infected mice also showed significant AHR in response to methacholine up to 154 days. This model provides a means to investigate the immunopathogenesis of RSV infection and its association with reactive airway disease.

Anti-respiratory syncytial virus (RSV) neutralizing antibody decreases lung inflammation, airway obstruction, and airway hyperresponsiveness in a murine RSV model.

Numerous studies have described a strong association between respiratory syncytial virus (RSV) infection in infancy and the development of recurrent wheezing and airway hyperresponsiveness. We evaluated the effect of an anti-RSV neutralizing monoclonal antibody (palivizumab) on different aspects of RSV disease by using a murine model. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or an isotype-matched control antibody was administered once at 24 h before inoculation, 1 h after inoculation, or 48 h after inoculation. Regardless of the timing of administration, all mice treated with the neutralizing antibody showed significantly decreased RSV loads in bronchoalveolar lavage (BAL) and lung specimens compared with those of infected controls. Pulmonary histopathologic scores, airway obstruction measured by plethysmography, and airway hyperresponsiveness after methacholine challenge were significantly reduced in mice treated with the anti-RSV antibody 24 h before inoculation compared with those for untreated controls. Concentrations of interferon-gamma, interleukin-10, macrophage inflammatory protein 1alpha, regulated on activation normal T-cell expressed and secreted (RANTES), and eotaxin in BAL fluids were also significantly reduced in mice treated with palivizumab 24 h before inoculation. This study demonstrates that reduced RSV replication was associated with significant modulation of inflammatory and clinical markers of acute disease severity and significant improvement of the long-term pulmonary abnormalities. Studies to determine whether strategies aimed at preventing or reducing RSV replication could decrease the long-term morbidity associated with RSV infection in children should be considered.

Opportunities for early therapy of respiratory syncytial virus (RSV) infection: what happens before hospitalization

RSV loads of infants are already declining near the time of hospitalization. For optimal effect, antiviral and other RSV therapeutics therefore may need to be applied before this occurs. 134 RSV-hospitalized infants were studied to determine the timing of events and their healthcare seeking behavior prior to hospitalization. Sixty-two percent of infants had contact with a health care professional ≥1 day prior to hospitalization and 46% had such a contact on ≥2 different days prior to hospitalization. The mean (S.D.) duration of RSV symptoms prior to hospitalization was 3.9±2.3 days and prior to first health care contact was 2.6±1.8 days. RSV-hospitalized infants routinely have contact with health care professionals at significantly early time points in their illness. These contacts are potential opportunities for initiation of early anti-RSV therapy.

Respiratory syncytial virus (RSV) loads in premature infants with and without prophylactic RSV fusion protein monoclonal antibody

It has not been determined whether respiratory syncytial virus (RSV) fusion protein monoclonal antibody (MAb) (palivizumab) reduces infection or simply ameliorates disease. In a prospective observational study, 27 hospitalized premature infants with RSV who were not receiving MAb were compared with 10 such patients who were receiving MAb. Mean (SEM) RSV loads in the MAb and non-MAb groups were 3.36 (0.59) versus 4.89 (0.27) logPFU/ml (P=.01). Prophylactic palivizumab reduces nasal RSV in premature hospitalized infants.

Inhalation efficacy of RFI-641 in an African green monkey model of RSV infection.

Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73-1.34 PFU/ml (P-value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection.