Vaccination of Cotton Rats with a Chimeric FG Glycoprotein of Human Respiratory Syncytial Virus Induces Minimal Pulmonary Pathology on Challenge

1991 ◽  
Vol 163 (3) ◽  
pp. 477-482 ◽  
Author(s):  
M. W. Wathen ◽  
T. J. Kakuk ◽  
R. J. Brideau ◽  
E. C. Hausknecht ◽  
S. L. Cole ◽  
...  
2020 ◽  
Vol 101 (10) ◽  
pp. 1056-1068
Author(s):  
Linda J. Rennick ◽  
Sham Nambulli ◽  
Ken Lemon ◽  
Grace Y. Olinger ◽  
Nicholas A. Crossland ◽  
...  

Human respiratory syncytial virus (HRSV) is an important respiratory pathogen causing a spectrum of illness, from common cold-like symptoms, to bronchiolitis and pneumonia requiring hospitalization in infants, the immunocompromised and the elderly. HRSV exists as two antigenic subtypes, A and B, which typically cycle biannually in separate seasons. There are many unresolved questions in HRSV biology regarding the interactions and interplay of the two subtypes. Therefore, we generated a reverse genetics system for a subtype A HRSV from the 2011 season (A11) to complement our existing subtype B reverse genetics system. We obtained the sequence (HRSVA11) directly from an unpassaged clinical sample and generated the recombinant (r) HRSVA11. A version of the virus expressing enhanced green fluorescent protein (EGFP) from an additional transcription unit in the fifth (5) position of the genome, rHRSVA11EGFP(5), was also generated. rHRSVA11 and rHRSVA11EGFP(5) grew comparably in cell culture. To facilitate animal co-infection studies, we derivatized our subtype B clinical isolate using reverse genetics toexpress the red fluorescent protein (dTom)-expressing rHRSVB05dTom(5). These viruses were then used to study simultaneous in vivo co-infection of the respiratory tract. Following intranasal infection, both rHRSVA11EGFP(5) and rHRSVB05dTom(5) infected cotton rats targeting the same cell populations and demonstrating that co-infection occurs in vivo. The implications of this finding on viral evolution are important since it shows that inter-subtype cooperativity and/or competition is feasible in vivo during the natural course of the infection.


Vaccine ◽  
1993 ◽  
Vol 11 (14) ◽  
pp. 1415-1423 ◽  
Author(s):  
Pedro A. Piedra ◽  
Philip R. Wyde ◽  
William L. Castleman ◽  
Mark W. Ambrose ◽  
Alan M. Jewell ◽  
...  

1995 ◽  
Vol 268 (6) ◽  
pp. L1006-L1011 ◽  
Author(s):  
G. N. Colasurdo ◽  
V. G. Hemming ◽  
G. A. Prince ◽  
J. E. Loader ◽  
J. P. Graves ◽  
...  

A dysfunction of the nonadrenergic noncholinergic inhibitory (NANCi) system has been invoked as a possible mechanism underlying or contributing to altered airway function. In the present study we assessed whether human respiratory syncytial virus (HRSV) infection affects the airways' neurally mediated contractile and relaxant (NANCi) responses in vitro. NANCi responses were studied on tracheal smooth muscle (TSM) segments obtained from young adult cotton rats, a well-established model for HRSV infection. To assess NANCi responses, TSM segments were removed and placed in tissue baths containing modified Krebs-Henseleit, atropine (1 x 10(-6) M) and propranolol (5 x 10(-6) M). After contraction with neurokinin A (1 x 10(-5) M), electrical field stimulation (EFS) was applied at stimulation frequencies ranging from 5 to 30 Hz. The NANCi responses were measured and expressed as the mean (+/- SE) percent relaxation. To evaluate neurally mediated contractile responses, full frequency response curves (0.5-30 Hz) to EFS were also performed. We found significantly decreased NANCi responses in TSM segments obtained from infected cotton rats (n = 12) compared with control animals (n = 9) (P < 0.002). Furthermore, the contractile responses to EFS were increased in infected animals compared with the control group (P = 0.0001). These findings demonstrate that HRSV infection leads to an enhanced contractile response to EFS and a significant decrease in NANCi response in cotton rat airways in vitro. This disruption of the neural control of airways may lead to the development of altered airway function.


2010 ◽  
Vol 7 (1) ◽  
Author(s):  
Myra N Widjojoatmodjo ◽  
Jolande Boes ◽  
Marleen van Bers ◽  
Yvonne van Remmerden ◽  
Paul JM Roholl ◽  
...  

2002 ◽  
Vol 46 (7) ◽  
pp. 2299-2302 ◽  
Author(s):  
Martin G. Ottolini ◽  
Spencer J. Curtis ◽  
David D. Porter ◽  
Amy Mathews ◽  
Joann Y. Richardson ◽  
...  

ABSTRACT Triamcinolone acetonide, methylprednisolone, and dexamethasone were each evaluated in combination with palivizumab (Synagis) for the therapy of established respiratory syncytial virus infection in the cotton rat. Triamcinolone and methylprednisolone proved to be more effective than dexamethasone in reducing lung pathology. No recurrence of viral replication or pulmonary pathology followed the cessation of therapy.


2020 ◽  
Vol 101 (10) ◽  
pp. 1037-1046 ◽  
Author(s):  
Laurine C. Rijsbergen ◽  
Linda J. Rennick ◽  
Brigitta M. Laksono ◽  
Peter R.W.A. van Run ◽  
Thijs Kuiken ◽  
...  

Human respiratory syncytial virus (HRSV) is the leading cause of severe respiratory tract disease in infants. Most HRSV infections remain restricted to the upper respiratory tract (URT), but in a small percentage of patients the infection spreads to the lower respiratory tract, resulting in bronchiolitis or pneumonia. We have a limited understanding of HRSV pathogenesis and what factors determine disease severity, partly due to the widespread use of tissue-culture-adapted viruses. Here, we studied early viral dissemination and tropism of HRSV in cotton rats, BALB/cJ mice and C57BL/6 mice. We used a novel recombinant (r) strain based on a subgroup A clinical isolate (A11) expressing EGFP [rHRSVA11EGFP(5)]. A recombinant laboratory-adapted HRSV strain [rHRSVA2EGFP(5)] was used as a direct comparison. Our results show that rHRSVA11EGFP(5) replicated to higher viral titres than laboratory-adapted rHRSVA2EGFP(5) in the URT of cotton rats and mice. HRSV-infected cells were detected as early as 2 days post-inoculation in both species in the nasal septa and lungs. Infection was predominantly present in ciliated epithelial cells in cotton rats and in the olfactory mucosa of mice. In our opinion, this study highlights that the choice of virus strain is important when studying HRSV pathogenesis in vivo and demonstrates that A11 is a representative clinical-based virus. Additionally, we show critical differences in tropism and inflammation when comparing HRSV infection of cotton rats and mice.


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