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doi: 10.7499/j.issn.1008-8830.2014.05.023

1 2 1
1. 2. 400014
HMPVHMPV
1 PRRs
HMPV PAMP Toll 3 4 I
F N

2014165548-554
Toll

Pathogenesis of human metapneumovirus infection and research on attenuated live

vaccine
TANG Mao-Zhi, DOU Ying, ZHAO Xiao-Dong. Department of Nephritic Immunology, Children's Hospital of Chongqing
Medical University, Chongqing 400014, China (Email: tmzm0130@163.com)
Abstract: Numerous studies have indicated that human metapneumovirus (hMPV) is an important viral pathogen
in acute respiratory infections in children, presenting similar manifestations with respiratory syncytial virus (RSV).
HMPV infection peaks in the winter-spring season and is more prevalent in younger ages, especially in children less than
1 year old. Host innate immune response has been implicated in recognition of pathogen-associated molecular patterns
(PAMPs) of the virus. This recognition occurs through host pattern recognition receptors (PRRs). Toll like receptors
(TLRs) are one of the largest class of PRRs which initiate and regulate adaptive immune responses. Some studies have
indicated that TLR 3 and TLR 4 may play critical roles in hMPV infection. Construction of recombinant mutant viruses
lacking one or two N-linked glycosylation sites in the F protein by using site-directed mutagenesis and reverse genetics
may be helpful for developing attenuated live vaccines.
[Chin J Contemp Pediatr, 2014, 16(5): 548-554]
Key words: Human metapneumovirus; Innate immunity; Toll-like receptor; Attenuated live vaccine

120

HMPV

[1]

WHO

[5] HMPV

5 [2] [3]

HMPV

RSV

HMPV

HMPV

RSV HMPV

[4]

3 1

2013-11-042014-02-09
cstc2013jjB10029

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1HMPV

70%~80%

HMPV 2001

HMPV A

2004

[21]HMPV RSV

HMPV HMPV Vero-E6

[4]

0~6

HMPV

HMPV IgG 6

HMPV

[6]

100 HMPV Ebihara

[7]

[5,24]

HMPV

2HMPV

14.6%~35.8%HMPV

HMPV 3' 5' N-P-M-F-M2-SH-

G-L 9 FG SH

NPL

HMPV 10%~27.8%6 ~2

HMPV

5.1%~8.2%2~6 4.5% >6

F G

0.2%~1.9%

[4,8-9]

[10-12]

RSV

1.7% HMPV

G SH

[13]

HMPV

HMPV

13 10 HMPV

G HMPV F

HMPV

[25-26] F

AB A1

RSV F

A2B1B2 2007~2011

HMPV F Arg-Gly-AspRGD

HMPV A2b

RGD

A2b

[9,15]

[14]

[16]

v1

2009~2010 B1

[27]HMPV

HMPV

F0

A2 A2aA2b

F1 F2 HMPV

A2b B2

F pH

A2

[5,28]F F

Li [23]

A2b A2

[28]Chang [29]

HRB H435 pH

pH H435

A2

MPRSS2

A1 B1

[12,17-22]

HMPV

F
[30]

RSV
30%~40%

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[40] RSV TLR3

3HMPV

gob5 mRNAIL-13 IL-5

[41]

HMPV A549

TLR3 TLR3 PolyI:C

HMPV HMPV

3.1HMPV

polyI:C TLR3 HMPV

[31]

[39,42]

TLR3 HMPV

TLR3 HMPV

TLR4 MyD88

TLR3 TRIF

NF-B I HMPV TLR4

HMPV

PRRs

I [31]

PAMPs

TLR7~9 MyD88

PRRs Toll TLRs

NF-B TRAF3

RLRs

7IRF7 I [5]

NLRs

HMPV HMPV

TLRs

TLR7~8 [39]

TLRs I

HMPV TLR7/8

[32-33]

TLRs

3.2HMPV

TLR3
dsRNATLR4 RSV F TLR7~8
ssRNA

[34-36]

TLR2

hMPV

A549 ,

HMPV TLR3~4TLR7~9

T CTL

IFN- TNF- ,

2~4

HA

[37]

[38-39]

TLRs

HMPV IRF-3 NF-B

FG SH HMPV

TLR3 RSV

AB 95%
[33]

TLR3

Skiadopoulos

ds-RNA MyD88

TRIF I

HMPV HMPV

[5]

HMPV SHG F

NF-B RSV

G SH

TLR3

HMPV F
550

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HMPV

[49] HMPV

CD3+CD4+CD25+CD8+CD19+

RSV HMPV F

CD19 CD23 NK

HMPV

[34-35]

HMPV [50]

HMPV

CD4+ CD8+T
CD4+T

5 HMPV

IL-6IL-1
TNF [36]

HMPV CTL Th2

HMPV

IL-4IL-10 IFN-

CTL CTL

HMPV [51-53]

Th1 IL-12 IFN-

cDNA

Th1

CTL HMPV

CTL HMPV

[39,43]

RSV

Th1/Th2 Th2

HMPV

Schowalter [26]
HMPV F

HMPV 4 F
3 57172353

HMPV

N- Western

Blot 3 WT F1

HMPV Th2

57172353

[5,54]

[44-45]

GFP HMPV

SH

NL/1/00WT cDNA

G M2-2

3 N-

6160 3200

M1 57 M2 172

4000

M3 353 M4

57+172 M5 172+353

[46]

M6 57+353 M7 57+172+353

HMPV SH rHMPV-

SHs 21

M1M2M4 M3M5M6M7

rHMPV-SHs

21 RSV F

353 353

[54]

[47-48]

M1M2M4 F

HMPV

[25]

Talaat

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WT
F

[54]

[55]

WT

Vero E6

WT 4

F HMPV

M1 WT

10 pfu/mL M2 M4

10 pfu/mL

F 57 172 353

M1 WT
M2M4 WT 1:110:1100:1

1000:1 Vero E6 M1 WT

N HMPV

M1 15
M2 WT 1:1 M2

1 HMPV

1 10:1

M2

M2 8 5
M2 100:1 1000:1

M4 M2

4 d M2 M4
WT 1:1 M4

1 10:1 M4
5 100:1 M4

M2

8 1000:1

5 d M4

201010106676 F

M2
F 172

WT M1

M2M4 M2 M4

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2014-06-03-034
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20~23 :

extracorporial membrane oxygenation, ECMO

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523900
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