Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts (original) (raw)
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Transmission of Human Respiratory Syncytial Virus in the Immunocompromised Ferret Model
Viruses, 2018
Human respiratory syncytial virus (HRSV) causes substantial morbidity and mortality in vulnerable patients, such as the very young, the elderly, and immunocompromised individuals of any age. Nosocomial transmission of HRSV remains a serious challenge in hospital settings, with intervention strategies largely limited to infection control measures, including isolation of cases, high standards of hand hygiene, cohort nursing, and use of personal protective equipment. No vaccines against HRSV are currently available, and treatment options are largely supportive care and expensive monoclonal antibody or antiviral therapy. The limitations of current animal models for HRSV infection impede the development of new preventive and therapeutic agents, and the assessment of their potential for limiting HRSV transmission, in particular in nosocomial settings. Here, we demonstrate the efficient transmission of HRSV from immunocompromised ferrets to both immunocompromised and immunocompetent contact ferrets, with pathological findings reproducing HRSV pathology in humans. The immunocompromised ferret-HRSV model represents a novel tool for the evaluation of intervention strategies against nosocomial transmission of HRSV.
Primary respiratory syncytial virus infection in mice
Journal of medical …, 1988
A mouse model of respiratory syncytial virus (RSV) infection is described. A high-titered, large-volume inoculum results in replication of RSV to a high titer in lungs of BALBic mice. Mice older than 15 weeks of age are more susceptible to RSV infection. Titers up to 106.9 plaque-forming units (pfu)/gram lung can be attained in 32-week-old mice. Older mice experience a clinical illness manifested by ruffled fur, reduced activity, and weight loss. Lung histology of older mice infected with RSV shows bronchiolitis and increased number of lymphocytes and macrophages in alveolar spaces compared with that of mice less than 8 weeks old. This model will serve as the basis for investigating immunodeterminants of recovery and protection from RSV infection.
Oral Efficacy of a Respiratory Syncytial Virus Inhibitor in Rodent Models of Infection
Antimicrobial Agents and Chemotherapy, 2004
Updated information and services can be found at: These include: REFERENCES http://aac.asm.org/content/48/7/2448#ref-list-1 at: This article cites 40 articles, 16 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders: http://journals.asm.org/site/subscriptions/ To subscribe to to another ASM Journal go to: on August 24, 2013 by guest http://aac.asm.org/
Bone Marrow Transplantation, 1999
Respiratory syncytial virus (RSV) has emerged as a leading cause of pneumonia, with high mortality, in bone marrow transplant (BMT) recipients, as well as in other profoundly immunocompromised patients, such as myelosuppressed adults with leukemia. We tested the efficacy of immunoglobulin with high anti-RSV neutralizing antibody levels (RSVIG) for prophylaxis and therapy of RSV infection in cotton rats undergoing prolonged immunosuppression with cyclophosphamide. These animals experience persistent infection, a model which is similar to the disease seen in post-BMT humans. Both prophylaxis and therapy reduced pulmonary viral replication over 500-fold to nearly undetectable levels. In animals receiving continual immunosuppression, the use of multiple therapeutic doses of RSVIG was able to prevent rebound viral replication, though virus was not completely eliminated.
A bovine model of vaccine enhanced respiratory syncytial virus pathophysiology
Vaccine, 1998
Keywords: bovine respiratory syncytial virus; vaccine Respiratory syncytial virus (RSV) is an important cause of respiratory tract disease in children and adults'. The disease induced by RSV in children less than 6 months of age commonly leads to hospitalization, often in intensive care, with pneumonia and severe bronchiolitis'. Indeed RSV has been increasingly cited as a major cause of morbidity and mortality in neonates and children with risk factors such as asthma and congenital heart defects. Recently there has been an increased awareness of the risk RSV presents for elderly and immunocompromised adults, in which infection can be fataP4.
Respiratory Syncytial Virus Affects Pulmonary Function in BALB/c Mice
The Journal of Infectious Diseases, 1998
BALB/c mice inoculated intranasally with respiratory syncytial virus (RSV) were studied in a whole-body plethysmograph to determine if signs of respiratory illness similar to those observed in human infants could be detected. Also, responsiveness to methacholine was assessed. RSV-infected mice showed significantly higher respiratory rates than did controls (409.2 vs. 305.2 breaths/min, P õ .0001). Significantly increased airway responsiveness to methacholine was noted, infected mice responding to a 100-fold lower dose than controls (P Å .003). Together, these data provide the first objective evidence of respiratory illness in the mouse model of RSV infection, which enhances the value of this model for evaluating effects of vaccines, antivirals, and other drugs acting on respiratory tract disease caused by RSV. cin B, and 5% (vol/vol) fetal calf serum. Cells and media were Respiratory syncytial virus (RSV) is the most important viral harvested when 80%-90% cytopathic effect was observed, sonipathogen causing respiratory tract disease in infants and young cated for 2 min with a high-output sonicator (Sonic 2000; Braun children [1-5]. Despite the clear importance of RSV in both Instruments, Burlingame, CA), and centrifuged for 10 min at 500 acute and chronic respiratory diseases of childhood, the underg. The supernatant was divided into small aliquots and quickly
A lamb model for human respiratory syncytial virus infection
Pediatric Pulmonology, 1993
Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in young children. The development of an animal model of RSV disease serves to better understanding the pathophysiology of airway disease from RSV infection in infants and children. Groups of six lambs were inoculated intratracheally (IT) or intranasally (IN) with a human strain of RSV (H-RSV). For controls 8 lambs received IT virus-free cell lysate. Tachypnea and fever were observed significantly more often following IT than following IN inoculation of H-RSV or IT placebo (for tachypnea: 20 of 69 days, 5 of 63 days, and 3 of 89 days, respectively, P < 0.001 ; for fever: 6 of 69 days, 0 of 63 days, and 1 of 89 days, respectively, P < 0.02). Nasal fluid production was significantly more frequent in both IT (1 4 of 69 days) and IN (1 5 of 63 days) groups than in the placebo group (2 of 87 days, P < 0.001). Postvaccination geometric mean titers (GMT, arithmetic transformation of log 2) of RSV-specific neutralizing antibody were significantly increased in the IT H-RSV group compared with postplacebo GMTs at 1 week (72 vs. 6.7, P < 0.03). By the second week postinoculation both H-RSV-infected groups had comparable levels of RSV-specific neutralizing antibody titers and had significantly greater GMTs for the second through to the fourth week than the placebo group (144, 128, and 4.8, respectively P < 0.0008). Bacterial isolates of the upper airway were comparable among the three groups. Histopathology at day 28 postinoculation was unremarkable for the three study groups. The development of overt clinical illness in lambs inoculated with H-RSV suggests that the H-RSV lamb model may be used to delineate the pathogenesis of lung injury of H-RSV infection.
The Journal of Infectious Diseases, 2021
BackgroundRespiratory syncytial virus (RSV) infections occur in human populations around the globe, causing disease of variable severity, disproportionately affecting infants and older adults (>65 years of age). Immune responses can be protective but also contribute to disease. Experimental studies in animals enable detailed investigation of immune responses, provide insights into clinical questions, and accelerate the development of passive and active vaccination. We aimed to review the role of antibody and T-cell responses in relation to RSV disease severity in animals.MethodsSystematic review and meta-analysis of animal studies examining the association between T-cell responses/phenotype or antibody titers and severity of RSV disease. The PubMed, Zoological Record, and Embase databases were screened from January 1980 to May 2018 to identify animal studies of RSV infection that assessed serum antibody titer or T lymphocytes with disease severity as an outcome. Sixty-three studi...