Unilateral nasal infection of cotton rats with respiratory syncytial virus allows assessment of local and systemic immunity

Johnson, Susan A.; Ottolini, Martin G.; Darnell, Miriam E. R.; Porter, David D.; Prince, Gregory A.

doi:10.1099/0022-1317-77-1-101

Cited by 11 publications

(4 citation statements)

References 14 publications

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“…Recently, Alvarez et al have reported efficient hMPV replication in lungs of BALB/c mice associated with transient weight loss (1). BALB/c mice and especially cotton rats are considered good and convenient experimental models to study the pathogenesis of human respiratory syncytial virus (hRSV), another paramyxovirus (7,11,12,19,22,24,45,46,50).…”

mentioning

confidence: 99%

Pathogenesis of Human Metapneumovirus Lung Infection in BALB/c Mice and Cotton Rats

Hamelin

Yim²,

Kuhn³

et al. 2005

J Virol

137

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Human metapneumovirus (hMPV) is a newly described member of the Paramyxoviridae family causing acute respiratory tract infections, especially in young children. We studied the pathogenesis of this viral infection in two experimental small animal models (BALB/c mice and cotton rats). Significant viral replication in the lungs of both animals was found following an intranasal challenge of 10 8 50% tissue culture infectious doses (TCID 50 ) and persisted for <2 and <3 weeks in the case of cotton rats and mice, respectively. Peak viral loads were found on day 5 postinfection in both mice (mean of 1.92 ؋ 10 7 TCID 50 /g lung) and cotton rats (mean of 1.03 ؋ 10 5 TCID 50 /g). Clinical symptoms consisting of breathing difficulties, ruffled fur, and weight loss were noted in mice only around the time of peak viral replication. Most significant pulmonary inflammatory changes and peak expression of macrophage inflammatory protein 1␣, gamma interferon, and RANTES occurred at the time of maximal viral replication (day 5) in both models. Cellular infiltration occurred predominantly around and within alveoli and persisted for at least 21 days in mice, whereas it was more limited in time with more peribronchiolitis in cotton rats. Both animal models would be of great value in evaluating different therapeutic agents, as well as vaccine candidates against hMPV.

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mentioning

confidence: 99%

Pathogenesis of Human Metapneumovirus Lung Infection in BALB/c Mice and Cotton Rats

Hamelin

Yim²,

Kuhn³

et al. 2005

J Virol

137

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“…Here, we examined the course of NP and ET infection by RSV in BALB/c mice by immunohistochemical methods, looking for cells expressing RSV antigens rather than scoring virus titers by plaque assay. An important departure from previous studies (21) was our method for inoculation (43,76) using a concentrated virus suspension and delivering the inoculum in multiple small aliquots over a 20-min interval. Unlike typical i.n.…”

Section: Resultsmentioning

confidence: 86%

“…Mice were infected i.n. following methodologies that were developed to deliver an inoculum specifically to the upper airway using a very small volume (43,76). Briefly, each mouse was lightly anesthetized, placed in a supine position, and given 10 7 PFU of RSV in a 20-l volume.…”

Section: Methodsmentioning

confidence: 99%

Chinchilla and Murine Models of Upper Respiratory Tract Infections with Respiratory Syncytial Virus

Gitiban

Jurcisek

Harris

et al. 2005

J Virol

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Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and the elderly. While the primary infection is the most serious, reinfection of the upper airway throughout life is the rule. Although relatively little is known about either RSV infection of the upper respiratory tract or host mucosal immunity to RSV, recent literature suggests that RSV is the predominant viral pathogen predisposing to bacterial otitis media (OM). Herein, we describe mouse and chinchilla models of RSV infection of the nasopharynx and Eustachian tube. Both rodent hosts were susceptible to RSV infection of the upper airway following intranasal challenge; however, the chinchilla proved to be more permissive than the mouse. The chinchilla model will likely be extremely useful to test the role of RSV in bacterial OM and the efficacy of RSV vaccine candidates designed to provide mucosal and cytotoxic T-lymphocyte immunity. Ultimately, we hope to investigate the relative ability of these candidates to potentially protect against viral predisposal to bacterial OM.Many factors contribute to the prevalence of middle ear infections in children as well as to the chronic or recurrent nature of otitis media (OM). These include immunological immaturity, existence of other infections, anatomic positioning of the Eustachian tube (ET), and genetic predisposition (10,14,22). However, whereas the multifactorial nature of OM is well known, it has only recently become fully appreciated that both acute and chronic OM are truly polymicrobial infections, involving any of several upper respiratory tract (URT) viruses and one or more of three bacterial pathogens.There is now ample epidemiological evidence and data generated by PCR-based assays, immunoassays, and direct culture to support the association of URT viruses with acute bacterial OM (2, 3, 15, 16, 39, 46-50, 55, 60, 64, 67-69). Moreover, peak incidence of OM occurs in concert with peak periods of viral isolation (38,56,64). Importantly, exposure to URT viruses (primarily via day care attendance or association with siblings) is a significant risk factor and/or predictor for early onset, frequent, or recurrent OM (51, 58). In a prospective study of 596 infants, Daly et al. (20) found that exposure to URT viruses is indisputably the single most important predictor for early acute OM. While the crucial role of URT viruses in the pathogenesis of bacterial OM is now firmly established (24, 32-36, 64, 65), we do not yet have a complete understanding of the mechanisms involved.Nearly all respiratory tract viruses can predispose to bacterial OM, but different viruses, and even different strains of the same virus, can differ in their relative ability to do so. The degree to which a particular virus compromises the airway, particularly the ET, has a tremendous influence on the occurrence and severity of OM (28,77). Whereas the cited studies describe intrastrain variability in the ability of influenza virus to predispose to OM, there are also ample data to suggest that othe...

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“…following methodologies that were developed to deliver an inoculum specifically to the upper airway using a very small volume (Johnson et al, 1996, Visweswaraiah et al, 2002. Briefly, each mouse was mildly anesthetized, placed in a supine position, and given 10 3 PFU of RSV in a 20-μl volume.…”

Section: Study Animals and Infectionmentioning

confidence: 99%

An Overview of Management of URTI and a Novel Approach Towards RSV Infection

Krishnamoorthy¹,

Ranjith²,

Gokulshankar³

et al. 2012

Respiratory Diseases

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Unilateral nasal infection of cotton rats with respiratory syncytial virus allows assessment of local and systemic immunity

Cited by 11 publications

References 14 publications

Pathogenesis of Human Metapneumovirus Lung Infection in BALB/c Mice and Cotton Rats

Pathogenesis of Human Metapneumovirus Lung Infection in BALB/c Mice and Cotton Rats

Chinchilla and Murine Models of Upper Respiratory Tract Infections with Respiratory Syncytial Virus

An Overview of Management of URTI and a Novel Approach Towards RSV Infection

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