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Common Cold, Uncommon Variation

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Common Cold, Uncommon Variation

生醫電資所 碩士班 楊謹榕 , M.D.

Instructor: Prof. 趙坤茂

(2)

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

(3)

Whole life, 80 years

Common cold,

5 years (6.3%)

(4)

Who is the enemy?

(5)

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%

(6)

Rhinovirus

Science, 27

th

March, 2009, Vol. 324, Issue 5923 Cover

Blue: vp1 Green: vp2 Red: vp3

(7)

Rhinovirus

• Discovered in the 19 50s

• Single-stranded, posi tive-sense RNA

30 nm

(8)

There is NO vaccine against Rhinovirus!

目前並沒有抗鼻病毒的疫苗

Against Influenza Virus

(9)

Genome of HRV (1)

VP: viral protein PRO: proteinase POL: polymerase

製作外殼 其他功能

(10)

Genotype Serotype 基因型

血清型

(11)

Palmenberg et al. 2009

Sequencing the full genomes of 99 HRV serotypes

(12)

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

(13)

將所有已知

的鼻病毒定

序,排列出

Genome Tree

(14)

PRT: pyrimidine-rich tract

IRES: internal ribosome entry site

UTR: untranslated region

(15)

“Uncommon Variation”

Pyrimidine-rich tract

• Different code in different HRV species

• Different code among isolates within the same serotype

(16)

Highly variable region: may be associated with pathological potential

Highly conserved region

(17)

Moreover

(18)

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

(19)

Recombination between HRV species

Huang T, et al. PLoS One. 2009 Jul 27;4(7):e6355

(20)

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

(21)

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?

(22)

Applications: Gene therapy?

• HRV target upper-airway m ucosa

• Generally, low comparative pathogenicity

• Broad antigenic diversity

(23)

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.

(24)

The End

2013/06/03

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