Latency and persistence of respiratory syncytial virus despite T cell immunity.
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.
Schwarze
Jurgen
J
Children's Clinic, St. Joseg-Hospital, Department of Medical Microbiology and Virology, Ruhr-Universität Bochum, Germany.
O'Donnell
Diarmund R
DR
Rohwedder
Angela
A
Openshaw
Peter J M
PJ
D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005260:Female; D007156:Immunologic Memory / Q000502:physiology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D017735:Virus Latency
D018984:Epitopes, T-Lymphocyte; D012367:RNA, Viral