Early Target Cells of Measles Virus after Aerosol Infection of Non-Human Primates
Measles virus (MV) is highly infectious, and has long been thought to enter the host by infecting epithelial cells of the respiratory tract. However, epithelial cells do not express signaling lymphocyte activation molecule (CD150), which is the high-affinity cellular receptor for wild-type MV strains. We have generated a new recombinant MV strain expressing enhanced green fluorescent protein (EGFP), based on a wild-type genotype B3 virus isolate from Khartoum, Sudan (KS). Cynomolgus macaques were infected with a high dose of rMVKSEGFP by aerosol inhalation to ensure that the virus could reach the full range of potential target cells throughout the entire respiratory tract. Animals were euthanized 2, 3, 4 or 5 days post-infection (d.p.i., n = 3 per time point) and infected (EGFP+) cells were identified at all four time points, albeit at low levels 2 and 3 d.p.i. At these earliest time points, MV-infected cells were exclusively detected in the lungs by fluorescence microscopy, histopathology and/or virus isolation from broncho-alveolar lavage cells. On 2 d.p.i., EGFP+ cells were phenotypically typed as large mononuclear cells present in the alveolar lumen or lining the alveolar epithelium. One to two days later, larger clusters of MV-infected cells were detected in bronchus-associated lymphoid tissue (BALT) and in the tracheo-bronchial lymph nodes. From 4 d.p.i. onward, MV-infected cells were detected in peripheral blood and various lymphoid tissues. In spite of the possibility for the aerosolized virus to infect cells and lymphoid tissues of the upper respiratory tract, MV-infected cells were not detected in either the tonsils or the adenoids until after onset of viremia. These data strongly suggest that in our model MV entered the host at the alveolar level by infecting macrophages or dendritic cells, which traffic the virus to BALT or regional lymph nodes, resulting in local amplification and subsequent systemic dissemination by viremia.
Vyšlo v časopise:
Early Target Cells of Measles Virus after Aerosol Infection of Non-Human Primates. PLoS Pathog 7(1): e32767. doi:10.1371/journal.ppat.1001263
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1001263
Souhrn
Measles virus (MV) is highly infectious, and has long been thought to enter the host by infecting epithelial cells of the respiratory tract. However, epithelial cells do not express signaling lymphocyte activation molecule (CD150), which is the high-affinity cellular receptor for wild-type MV strains. We have generated a new recombinant MV strain expressing enhanced green fluorescent protein (EGFP), based on a wild-type genotype B3 virus isolate from Khartoum, Sudan (KS). Cynomolgus macaques were infected with a high dose of rMVKSEGFP by aerosol inhalation to ensure that the virus could reach the full range of potential target cells throughout the entire respiratory tract. Animals were euthanized 2, 3, 4 or 5 days post-infection (d.p.i., n = 3 per time point) and infected (EGFP+) cells were identified at all four time points, albeit at low levels 2 and 3 d.p.i. At these earliest time points, MV-infected cells were exclusively detected in the lungs by fluorescence microscopy, histopathology and/or virus isolation from broncho-alveolar lavage cells. On 2 d.p.i., EGFP+ cells were phenotypically typed as large mononuclear cells present in the alveolar lumen or lining the alveolar epithelium. One to two days later, larger clusters of MV-infected cells were detected in bronchus-associated lymphoid tissue (BALT) and in the tracheo-bronchial lymph nodes. From 4 d.p.i. onward, MV-infected cells were detected in peripheral blood and various lymphoid tissues. In spite of the possibility for the aerosolized virus to infect cells and lymphoid tissues of the upper respiratory tract, MV-infected cells were not detected in either the tonsils or the adenoids until after onset of viremia. These data strongly suggest that in our model MV entered the host at the alveolar level by infecting macrophages or dendritic cells, which traffic the virus to BALT or regional lymph nodes, resulting in local amplification and subsequent systemic dissemination by viremia.
Zdroje
1. GriffinDE
2007 Measles virus.
KnipeDM
HowleyPM
Fields Virology Philadelphia Lippincott Williams & Wilkins 1551 1585
2. WHO 2009 Global reductions in measles mortality 2000–2008 and the risk of measles resurgence. Wkly Epidemiol Rec 84 509 516
3. SmithEC
PopaA
ChangA
MasanteC
DutchRE
2009 Viral entry mechanisms: the increasing diversity of paramyxovirus entry. FEBS J 276 7217 7227
4. DörigRE
MarcilA
ChopraA
RichardsonCD
1993 The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 75 295 305
5. NanicheD
Varior-KrishnanG
CervoniF
WildTF
RossiB
1993 Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol 67 6025 6032
6. BucklandR
WildTF
1997 Is CD46 the cellular receptor for measles virus? Virus Res 48 1 9
7. TatsuoH
OnoN
TanakaK
YanagiY
2000 SLAM (CDw150) is a cellular receptor for measles virus. Nature 406 893 897
8. YanagiY
TakedaM
OhnoS
SekiF
2006 Measles virus receptors and tropism. Jpn J Infect Dis 59 1 5
9. LeonardVHJ
SinnPL
HodgeG
MiestT
DevauxP
2008 Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed. J Clin Invest 118 2448 2458
10. TaharaM
TakedaM
ShiroganeY
HashiguchiT
OhnoS
2008 Measles virus infects both polarized epithelial and immune cells using distinctive receptor-binding sites on its hemagglutinin. J Virol 82 4630 4637
11. TakedaM
TaharaM
HashiguchiT
SatoTA
JinnouchiF
2007 A human lung carcinoma cell line supports efficient measles virus growth and syncytium formation via SLAM- and CD46-independent mechanism. J Virol 81 12091 12096
12. TakedaM
TakeuchiK
MiyajimaN
KobuneF
AmiY
2000 Recovery of pathogenic measles virus from cloned cDNA. J Virol 74 6643 6647
13. HashimotoK
OnoN
TatsuoH
MinagawaH
TakedaM
2002 SLAM (CD150)-independent measles virus entry as revealed by recombinant virus expressing green fluorescent protein. J Virol 76 6743 6749
14. De SwartRL
LudlowM
De WitteL
YanagiY
Van AmerongenG
2007 Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques. PLoS Pathog 3 e178
15. LeonardVH
HodgeG
Reyes-delVJ
McChesneyMB
CattaneoR
2010 Measles virus selectively blind to signaling lymphocytic activation molecule (SLAM; CD150) is attenuated and induces strong adaptive immune responses in rhesus monkeys. J Virol 84 3413 3420
16. LudlowM
RennickL
SarlangS
SkibinskiG
McQuaidS
2010 Wild-type measles virus infection of primary epithelial cells occurs via the basolateral surface without syncytium formation or release of infectious virus. J Gen Virol 91 971 979
17. ShiroganeY
TakedaM
TaharaM
IkegameS
NakamuraT
2010 Epithelial-mesenchymal transition abolishes the susceptibility of polarized epithelial cell lines to measles virus. J Biol Chem 285 20882 20890
18. Von MesslingV
SvitekN
CattaneoR
2006 Receptor (SLAM [CD150]) recognition and the V protein sustain swift lymphocyte-based invasion of mucosal tissue and lymphatic organs by a morbillivirus. J Virol 80 6084 6092
19. De WitteL
AbtM
Schneider-SchauliesS
van KooykY
GeijtenbeekTBH
2006 Measles virus targets DC-SIGN to enhance dendritic cell infection. J Virol 80 3477 3486
20. De WitteL
De VriesRD
Van der VlistM
YükselS
LitjensM
2008 DC-SIGN and CD150 have distinct roles in transmission of measles virus from dendritic cells to T-lymphocytes. PLoS Pathog 4 e1000049
21. El MubarakHS
Van de BildtMWG
MustafaOA
VosHW
MukhtarMM
2000 Serological and virological characterization of clinically diagnosed cases of measles in suburban Khartoum. J Clin Microbiol 38 987 991
22. El MubarakHS
Van de BildtMWG
MustafaOA
VosHW
MukhtarMM
2002 Genetic characterisation of wild type measles viruses circulating in suburban Khartoum, 1997–2000. J Gen Virol 83 1437 1443
23. IbrahimSA
MustafaOM
MukhtarMM
SalehIA
El MubarakHS
2002 Measles in suburban Khartoum: an epidemiological and clinical study. Trop Med Int Health 7 442 449
24. El MubarakHS
YükselS
Van AmerongenG
MulderPGH
MukhtarMM
2007 Infection of cynomolgus macaques (Macaca fascicularis) and rhesus macaques (Macaca mulatta) with different wild-type measles viruses. J Gen Virol 88 2028 2034
25. De VriesRD
LemonK
LudlowM
McQuaidS
YukselS
2010 In vivo tropism of attenuated and pathogenic measles virus expressing green fluorescent protein in macaques. J Virol 84 4714 4724
26. Von MesslingV
MilosevicD
CattaneoR
2004 Tropism illuminated: lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system. Proc Natl Acad Sci USA 101 14216 14421
27. KawamataN
XuB
NishijimaH
AoyamaK
KusumotoM
2009 Expression of endothelia and lymphocyte adhesion molecules in bronchus-associated lymphoid tissue (BALT) in adult human lung. Respir Res 10 97
28. FerreiraCS
FrenzkeM
LeonardVH
WelsteadGG
RichardsonCD
2010 Measles virus infection of alveolar macrophages and dendritic cells precedes spread to lymphatic organs in transgenic mice expressing human signaling lymphocytic activation molecule (SLAM, CD150). J Virol 84 3033 3042
29. SternbergS
1997 Histology for pathologists Philadelphia Lippincott & Raven 1200
30. PabstR
TschernigT
2010 Bronchus-associated lymphoid tissue: an entry site for antigens for successful mucosal vaccinations? Am J Respir Cell Mol Biol 43 137 141
31. ToyoshimaM
ChidaK
SatoA
2000 Antigen uptake and subsequent cell kinetics in bronchus-associated lymphoid tissue. Respirology 5 141 145
32. TeitelbaumR
SchubertW
GuntherL
KressY
MacalusoF
1999 The M cell as a portal of entry to the lung for the bacterial pathogen Mycobacterium tuberculosis. Immunity 10 641 650
33. MorinMJ
WarnerA
FieldsBN
1994 A pathway for entry of reoviruses into the host through M cells of the respiratory tract. J Exp Med 180 1523 1527
34. LemonK
RimaBK
McQuaidS
AllenIV
DuprexWP
2007 The F gene of rodent brain-adapted mumps virus is a major determinant of neurovirulence. J Virol 81 8293 8302
35. DubusJC
VecellioL
De MonteM
FinkJB
GrimbertD
2005 Aerosol deposition in neonatal ventilation. Pediatr Res 58 10 14
36. El MubarakHS
De SwartRL
OsterhausADME
SchuttenM
2005 Development of a semi-quantitative real-time RT-PCR for the detection of measles virus. J Clin Virol 32 313 317
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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