Common Cold, Uncommon Variation
生醫電資所 碩士班 楊謹榕 , M.D.
Instructor: Prof. 趙坤茂
Common Cold,
Uncommon Variation
• Gregory A. Poland, M.D., and Mich ael A. Barry, Ph.D.
• New England Journal of Medicine 2009;360(21): 2245-6
Whole life, 80 years
Common cold,
5 years (6.3%)
Who is the enemy?
Common Pathogens of Common Cold
PIV: parainfluenza virus, RSV: respiratory syncytial virus, MPV: metapneumovirus, Group A Strept: group A streptococcal disease.
Rhinovirus
鼻病毒 50-
80%
Rhinovirus
Science, 27
thMarch, 2009, Vol. 324, Issue 5923 Cover
Blue: vp1 Green: vp2 Red: vp3
Rhinovirus
• Discovered in the 19 50s
• Single-stranded, posi tive-sense RNA
30 nm
There is NO vaccine against Rhinovirus!
目前並沒有抗鼻病毒的疫苗
Against Influenza Virus
Genome of HRV (1)
VP: viral protein PRO: proteinase POL: polymerase
製作外殼 其他功能
Genotype Serotype 基因型
血清型
Palmenberg et al. 2009
Sequencing the full genomes of 99 HRV serotypes
Palmenberg et al. 2009
Whole genome amino acid sequence identity comparison
HRV-A HRV-B
HRV-C HRV-A
HRV-C HRV-B
比較不同血清型的 鼻病毒的胺基酸序 列
將所有已知
的鼻病毒定
序,排列出
Genome Tree
PRT: pyrimidine-rich tract
IRES: internal ribosome entry site
UTR: untranslated region
“Uncommon Variation”
Pyrimidine-rich tract
• Different code in different HRV species
• Different code among isolates within the same serotype
Highly variable region: may be associated with pathological potential
Highly conserved region
Moreover
Recombination between HRV species
相 似 程 度
Hrv-53 Hrv-80 Hrv-46
Palmenberg AC, J Allergy Clin Immunol. 2010 Jun;125(6):1190-9
Recombination between HRV species
Huang T, et al. PLoS One. 2009 Jul 27;4(7):e6355
Recombinations between HRV species
• Variations in nasal-wash i solates from patients wit h the same serotype HRV infection
• Prolonged course
• Poor therapeutic efficacy of antiviral drug
Applications: Vaccine
• Influenza: trivalent vaccine (2A1B)
三價流感疫苗:對抗兩種 A 型流感 病毒,一種 B 型流感病毒
• Rhinovirus: multivalent vaccine?
鼻病毒:多價疫苗,一次對抗多種 病毒?
Applications: Gene therapy?
• HRV target upper-airway m ucosa
• Generally, low comparative pathogenicity
• Broad antigenic diversity
Take Home Message
• Rhinovirus is the major pathogen of common c old.
• Pyrimidine-rich tract is highly variable among r hinovirus.
• Recombination increases the variability of rhin ovirus.
• Genome variation increases the pathogenic po tential of rhinovirus.