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Latency and Persistence of Respiratory Syncytial Virus Despite T Cell Immunity

Children's Clinic, St. Josef-Hospital; Department of Medical Microbiology and Virology, Ruhr-Universität Bochum, Bochum, Germany; and Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom

Correspondence and requests for reprints should be addressed to Peter J. M. Openshaw, M.D., Department of Respiratory Medicine, Imperial College London, Norfolk Place, Paddington, London W2 1PG, UK. E-mail: p.openshaw{at}ic.ac.uk

Respiratory syncytial virus (RSV) 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 RSV, 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 nonmutated M2 82–91 K^d cytotoxic T lymphocyte epitope. A mutation of this epitope, detected in one clone, did not assist evasion. We suggest that RSV 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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