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.
BACKGROUND
Respiratory syncytial virus (RSV) can cause prolonged infections in individuals with compromised immunity.


OBJECTIVE
To investigate whether RSV evolves during prolonged infection in an immunocompromised host.


METHODS
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.


CONCLUSIONS
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.
Lazar
Isaac
I
Department of Pediatrics, Section of Critical Care, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, United States. isaac.lazar@yale.edu
Canaan
Allon
A
Weibel
Carla
C
Kahn
Jeffrey S
JS
D000595:Amino Acid Sequence; D002675:Child, Preschool; D005260:Female; D005814:Genes, Viral; D006801:Humans; D016867:Immunocompromised Host; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000628:therapy*; D014759:Viral Envelope Proteins / Q000235:genetics; D017201:Virus Shedding / Q000235:genetics
D016756:Immunoglobulins, Intravenous; D014759:Viral Envelope Proteins