Gene expression profiles during in vivo human rhinovirus infection: insights into the host response.
BACKGROUND
Human rhinovirus infections cause colds and trigger exacerbations of lower airway diseases.


OBJECTIVE
To define changes in gene expression profiles during in vivo rhinovirus infections.


METHODS
Nasal epithelial scrapings were obtained before and during experimental rhinovirus infection, and gene expression was evaluated by microarray. Naturally acquired rhinovirus infections, cultured human epithelial cells, and short interfering RNA knockdown were used to further evaluate the role of viperin in rhinovirus infections.


RESULTS
Symptom scores and viral titers were measured in subjects inoculated with rhinovirus or sham control, and changes in gene expression were assessed 8 and 48 hours after inoculation. Real-time reverse transcription-polymerase chain reaction for viperin and rhinoviruses was used in naturally acquired infections, and viperin mRNA levels and viral titers were measured in cultured cells. Rhinovirus-induced changes in gene expression were not observed 8 hours after viral infection, but 11,887 gene transcripts were significantly altered in scrapings obtained 2 days postinoculation. Major groups of up-regulated genes included chemokines, signaling molecules, interferon-responsive genes, and antivirals. Viperin expression was further examined and also was increased in naturally acquired rhinovirus infections, as well as in cultured human epithelial cells infected with intact, but not replication-deficient, rhinovirus. Knockdown of viperin with short interfering RNA increased rhinovirus replication in infected epithelial cells.


CONCLUSIONS
Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.
Proud
David
D
Department of Physiology and Biophysics, Health Sciences 1626, University of Calgary Faculty of Medicine, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1 Canada. dproud@ucalgary.ca
Turner
Ronald B
RB
Winther
Birgit
B
Wiehler
Shahina
S
Tiesman
Jay P
JP
Reichling
Tim D
TD
Juhlin
Kenton D
KD
Fulmer
Andy W
AW
Ho
Begonia Y
BY
Walanski
Amy A
AA
Poore
Cathy L
CL
Mizoguchi
Haruko
H
Jump
Lynn
L
Moore
Marsha L
ML
Zukowski
Claudine K
CK
Clymer
Jeffrey W
JW
D000293:Adolescent; D018929:Cell Culture Techniques; D018925:Chemokines / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010850:Picornaviridae Infections / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000235:genetics*; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult; D000090123:Viperin Protein
D018925:Chemokines; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; C444427:RSAD2 protein, human; D000090123:Viperin Protein