TY - JOUR
T1 - Novel mutations in the respiratory syncytial virus G gene identified in viral isolates from a girl with severe combined immune deficiency treated with intravenous immune globulin
AU - Lazar, Isaac
AU - Canaan, Allon
AU - Weibel, Carla
AU - Kahn, Jeffrey
N1 - Funding Information:
Grant support: this work was supported by The Patrick and Catherine Weldon Donaghue Medical Research Foundation. This work was also supported in part by the Yale Children's Clinical Research Center grant M01-RR06022, General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health.
PY - 2006/11
Y1 - 2006/11
N2 - Background: Respiratory syncytial virus (RSV) can cause prolonged infections in individuals with compromised immunity. Objectives: To investigate whether RSV evolves during prolonged infection in an immunocompromised host. Study design: We sequenced the envalope glycoprotein genes of RSV obtained at three time points during a 59-day period from a 4-year-old female with severe combined immune deficiency (SCID) treated with intravenous immunoglobulin (IVIG). Results: Sporadic silent mutations were found in the SH, G and F genes among three RSV samples collected at days 0, 19 and 59. Premature stop codons at amino acid positions 257 and 278 were present in the RSV G glycoprotein gene sequenced from each time point. None of the 48 RSV G sequences available on GenBank or any of 50 genetically diverse clinical isolates of RSV contained these mutations. These premature stop codon mutations occurred at the same positions of the G glycoprotein gene as those described in in vitro monoclonal-antibody resistant mutants reported elsewhere. Conclusion: Our patient was most likely infected with a single RSV strain that did not mutate during the study period. This strain contains unique mutations that may have previously evolved in this individual who had prolonged infection and was treated with monthly IVIG.
AB - Background: Respiratory syncytial virus (RSV) can cause prolonged infections in individuals with compromised immunity. Objectives: To investigate whether RSV evolves during prolonged infection in an immunocompromised host. Study design: We sequenced the envalope glycoprotein genes of RSV obtained at three time points during a 59-day period from a 4-year-old female with severe combined immune deficiency (SCID) treated with intravenous immunoglobulin (IVIG). Results: Sporadic silent mutations were found in the SH, G and F genes among three RSV samples collected at days 0, 19 and 59. Premature stop codons at amino acid positions 257 and 278 were present in the RSV G glycoprotein gene sequenced from each time point. None of the 48 RSV G sequences available on GenBank or any of 50 genetically diverse clinical isolates of RSV contained these mutations. These premature stop codon mutations occurred at the same positions of the G glycoprotein gene as those described in in vitro monoclonal-antibody resistant mutants reported elsewhere. Conclusion: Our patient was most likely infected with a single RSV strain that did not mutate during the study period. This strain contains unique mutations that may have previously evolved in this individual who had prolonged infection and was treated with monthly IVIG.
KW - Clinical isolates
KW - G glycoprotein mutations
KW - IVIG
KW - Premature stop codon
KW - Respiratory infections
KW - Respiratory syncytial virus
KW - SCID
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U2 - 10.1016/j.jcv.2006.07.006
DO - 10.1016/j.jcv.2006.07.006
M3 - Article
C2 - 16949862
AN - SCOPUS:33749621463
SN - 1386-6532
VL - 37
SP - 168
EP - 173
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
IS - 3
ER -