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Published ahead of print on January 23, 2004, doi:10.1164/rccm.200308-1203OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 7, April 2004, 801-805

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Submitted on September 3, 2003
Accepted on January 16, 2004

Latency and Persistence of Respiratory Syncytial Virus Despite T cell Immunity

Jurgen Schwarze1, Diarmund R O'Donnell2, Angela Rohwedder3, and Peter JM Openshaw2*

1 Children's Clinic, St. Josef-Hospital, Bochum, Germany; Respiratory Medicine, National Heart and Lung Institute, Imperial College, London, England, United Kingdom, 2 Respiratory Medicine, National Heart and Lung Institute, Imperial College, London, England, United Kingdom, 3 Medical Microbiology and Virology, Ruhr-Universitat, Bochum, Germany

* To whom correspondence should be addressed. E-mail: p.openshaw{at}ic.ac.uk.

Respiratory syncytial virus causes bronchiolitis in infants, which is associated with recurrent wheezing in later childhood. There is mounting evidence that the virus becomes latent or persists in vivo, but little is known about the mechanisms of its latency, persistence, and immune evasion. We therefore infected BALB/c mice intranasally with human respiratory syncytial virus, analyzed sequential tissue samples by direct culture and polymerase chain reaction for viral and messenger RNA and monitored antiviral immune responses. Virus could not be detected in bronchoalveolar lavage samples beyond day 14, but viral genomic and messenger RNA was present in lung homogenates for 100 days or more; combined depletion of CD4 and CD8 T cells allowed infective virus to be recovered. Neutralizing antibody and memory cytotoxic T cell responses were intact in mice with latent infections, and latent viral genome contained an authentic non-mutated M2 82-91 Kd cytotoxic T-lymphocyte epitope. A mutation of this epitope, detected in one clone, did not assist evasion. We suggest that respiratory syncytial virus latency depends on persistence in privileged sites rather than on viral mutation.
Key words: Respiratory Syncytial Viruses, Virus Latency, CD8-Positive T-Lymphocytes




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