Speculation on Pathogenesis in Death from Respiratory Syncytial Virus Infection

Gardner, P. S.; McQuillin, Joyce; Court, S. D. M.

doi:10.1136/bmj.1.5692.327

Cited by 147 publications

(52 citation statements)

References 8 publications

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“…However, in the present survey, most infants infected with RS virus had only a mild upper respiratory illness, suggesting that factors other than the nature of the virus and the age of the child are concerned in the development of bronchiolitis. The heightened response to infection in children who had previously received inactivated RS vaccine (Kapikian et al 1969) and the demonstration of immune complexes in the lungs of fatal cases of bronchiolitis (Gardner, McQuillin & Court, 1970) suggest an immunological mechanism.…”

Section: Relations Between Agents and Clinical Featuresmentioning

confidence: 99%

Respiratory viral infection in childhood. A survey in general practice, Roehampton 1967–1972

Horn

Brain

Gregg

et al. 1975

J. Hyg.

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SUMMARYThe role of viruses and M. pneumoniae in episodes of acute respiratory illness in childhood has been studied in a London general practice. The total isolation rate was 31P7 %, but the rate varied from 32-6 % in upper respiratory infections to 640% in pneumonia. The clinical features associated with infection were influenced not only by the type of agent but also by age and other host factors in the infected children. Rhinoviruses were more commonly isolated than any other agent and were frequently associated with wheezy bronchitis.

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Section: Relations Between Agents and Clinical Featuresmentioning

confidence: 99%

Respiratory viral infection in childhood. A survey in general practice, Roehampton 1967–1972

Horn

Brain

Gregg

et al. 1975

J. Hyg.

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“…Although viral antigens have been detected in circulating mononuclear cells, the virus does not cause a viremia (13). Autopsy histopathologic studies of infected individuals suggest that viral antigen does not penetrate further than the superficial layers of the respiratory epithelium in immunocompetent individuals (14). Additionally, the cellular syncytia that are frequently observed in nonpolarized cells in vitro are rarely noted in pathologic specimens.…”

mentioning

confidence: 99%

Apical recycling systems regulate directional budding of respiratory syncytial virus from polarized epithelial cells

Brock

Goldenring

Crowe

2003

Proc. Natl. Acad. Sci. U.S.A.

104

114

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Respiratory syncytial virus (RSV) is the major viral cause of serious lower respiratory tract illness in infants and young children worldwide. RSV infection is limited to the superficial layers of the respiratory epithelium in immunocompetent individuals. Consistent with this in vivo observation, we and others have found that RSV buds preferentially from the apical surface of infected polarized epithelial cells. In contrast, directional budding is not observed in nonpolarized human epithelial cells. These findings suggest that RSV uses specific cellular trafficking pathways to accomplish viral replication. The host cell proteins that regulate directional budding of RSV are undefined. Apical sorting of cellular proteins in polarized epithelial cells involves the apical recycling endosome (ARE). To investigate whether ARE-mediated protein sorting plays a role during RSV replication, we expressed a fragment of the myosin Vb tail that functions as a dominant negative inhibitor of ARE-mediated protein sorting in polarized Madin-Darby canine kidney cells. When these cells were infected with RSV, a >9,000-fold reduction in viral yield was observed. A similar effect on virus replication was observed when a carboxyl-terminal fragment of another AREassociated protein, the Rab11 family interacting protein 1, was expressed in Madin-Darby canine kidney cells. These data suggest that RSV requires proper ARE-mediated protein sorting for efficient egress from the apical surface of polarized epithelial cells.

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“…It is also a major underappreciated contributor to morbidity and mortality in elderly and immunosuppressed adults (2). Although RSV infection is essentially confined to the respiratory epithelium, extensive lung inflammation frequently causes lifethreatening disease in these at-risk populations (3,4). It remains one of the few common severe infections for which there is no specific intervention and an effective vaccine represents a major unmet need.…”

mentioning

confidence: 99%

Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus

Habibi

Jóźwik

Makris

et al. 2015

Am J Respir Crit Care Med

230

263

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Rationale: Despite relative antigenic stability, respiratory syncytial virus (RSV) reinfects throughout life. After more than 40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection.Objectives: To characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development.Methods: We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B-cell frequencies and antibody longevity.Measurements and Main Results: Despite moderately high levels of preexisting serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from polymerase chain reaction-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects but correlated with plasmablasts that peaked around Day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, in which virus-specific IgA memory B cells were readily recovered.Conclusions: This observed specific defect in IgA memory may partly explain the ability of RSV to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone.

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Speculation on Pathogenesis in Death from Respiratory Syncytial Virus Infection

Cited by 147 publications

References 8 publications

Respiratory viral infection in childhood. A survey in general practice, Roehampton 1967–1972

Respiratory viral infection in childhood. A survey in general practice, Roehampton 1967–1972

Apical recycling systems regulate directional budding of respiratory syncytial virus from polarized epithelial cells

Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus

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