C. L. Afonso, G. K. Amarasinghe, K. Banyai, Y. Bao, C. F. Basler et al., Taxonomy of the order Mononegavirales: update, vol.161, pp.2351-60, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01911212

, , p.27216929

J. B. Domachowske and H. F. Rosenberg, Respiratory syncytial virus infection: immune response, immunopathogenesis, and treatment, Clin Microbiol Rev, vol.12, p.10194461, 1999.
DOI : 10.1128/cmr.12.2.298

URL : https://cmr.asm.org/content/cmr/12/2/298.full.pdf

G. Boivin, Y. Abed, G. Pelletier, L. Ruel, D. Moisan et al., Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups, J Infect Dis, vol.186, pp.1330-1334, 2002.

P. L. Collins and B. S. Graham, Viral and host factors in human respiratory syncytial virus pathogenesis, J Virol, vol.82, pp.2040-55, 2008.
DOI : 10.1128/jvi.01625-07

URL : https://jvi.asm.org/content/82/5/2040.full.pdf

H. Nair, D. J. Nokes, B. D. Gessner, M. Dherani, S. A. Madhi et al., Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis, Lancet, vol.375, pp.1545-55, 2010.

P. M. Hansbro, M. R. Starkey, J. Mattes, and J. C. Horvat, Pulmonary immunity during respiratory infections in early life and the development of severe asthma, Ann Am Thorac Soc, vol.11, issue.5, p.25525736, 2014.


I. Rudan, K. L. O'brien, H. Nair, L. Liu, E. Theodoratou et al., Epidemiology and etiology of childhood pneumonia in 2010: estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries, J Glob Health, vol.3, p.23826505, 2013.


R. Lozano, M. Naghavi, K. Foreman, S. Lim, K. Shibuya et al., Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study, Lancet, vol.380, pp.61728-61728, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00827612

M. Beem, F. H. Wright, D. Hamre, R. Egerer, and M. Oehme, Association of the chimpanzee coryza agent with acute respiratory disease in children, N Engl J Med, vol.263, pp.523-553, 1960.

R. E. Blount, . Jr, J. A. Morris, and R. E. Savage, Recovery of cytopathogenic agent from chimpanzees with coryza, Proc Soc Exp Biol Med, vol.92, p.13359460, 1956.


R. Chanock and L. Finberg, Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). II. Epidemiologic aspects of infection in infants and young children, Am J Hyg, vol.66, p.13478579, 1957.

R. Chanock, B. Roizman, and R. Myers, Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization, Am J Hyg, vol.66, pp.281-90, 1957.

E. E. Walsh and J. Hruska, Monoclonal antibodies to respiratory syncytial virus proteins: identification of the fusion protein, J Virol, vol.47, p.6345804, 1983.

J. S. Kahn, Human metapneumovirus, a newly emerging respiratory virus, Pediatr Infect Dis J, vol.22, pp.923-927, 2003.


M. S. Collins and R. E. Gough, Characterization of a virus associated with turkey rhinotracheitis, J Gen Virol, vol.69, pp.909-925, 1988.

J. K. Cook, Avian pneumovirus infections of turkeys and chickens, Vet J, vol.160, p.10985803, 2000.

, , pp.90486-90492

M. De-graaf, A. D. Osterhaus, R. A. Fouchier, and E. C. Holmes, Evolutionary dynamics of human and avian metapneumoviruses, J Gen Virol, vol.89, pp.2933-2975, 2008.

, PMID, 19008378.


V. Schildgen, B. Van-den-hoogen, R. Fouchier, R. A. Tripp, R. Alvarez et al., Human Metapneumovirus: lessons learned over the first decade, Clin Microbiol Rev, vol.24, p.21976607, 2011.


F. Feuillet, B. Lina, M. Rosa-calatrava, and G. Boivin, Ten years of human metapneumovirus research, J Clin Virol, vol.53, pp.97-105, 2012.

G. Boivin, D. Serres, G. Hamelin, M. E. Cote, S. Argouin et al., An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility, Clin Infect Dis, vol.44, pp.1152-1160, 2007.

, , p.17407031

L. Bont, J. Versteegh, W. T. Swelsen, C. J. Heijnen, A. Kavelaars et al., Natural reinfection with respiratory syncytial virus does not boost virus-specific T-cell immunity, Pediatr Res, vol.52, pp.363-370, 2002.


J. A. Pavlin, A. C. Hickey, N. Ulbrandt, Y. P. Chan, T. P. Endy et al., Human metapneumovirus reinfection among children in Thailand determined by ELISA using purified soluble fusion protein, J Infect Dis, vol.198, pp.836-878, 2008.

A. R. Falsey and E. E. Walsh, Respiratory syncytial virus infection in adults, Clin Microbiol Rev, vol.13, p.10885982, 2000.


L. Haas, S. Thijsen, L. Van-elden, and K. A. Heemstra, Human Metapneumovirus in Adults, Viruses, vol.5, pp.87-110, 2013.

E. E. Walsh, D. R. Peterson, and A. R. Falsey, Human metapneumovirus infections in adults: another piece of the puzzle, Arch Intern Med, vol.168, pp.2489-96, 2008.


P. F. Cespedes, P. A. Gonzalez, and A. M. Kalergis, Human metapneumovirus keeps dendritic cells from priming antigenspecific naive T cells, Immunology, vol.139, pp.366-76, 2013.


P. A. Gonzalez, C. E. Prado, E. D. Leiva, L. J. Carreno, S. M. Bueno et al., Respiratory syncytial virus impairs T cell activation by preventing synapse assembly with dendritic cells, Proc Natl Acad Sci U S A, vol.105, pp.14999-5004, 2008.

, , p.18818306

P. De-graaff, E. C. De-jong, T. M. Van-capel, M. Van-dijk, P. Roholl et al., Respiratory syncytial virus infection of monocyte-derived dendritic cells decreases their capacity to activate CD4 T cells, J Immunol, vol.175, pp.5904-5915, 2005.

L. Nou?-en, C. Hillyer, P. Brock, L. G. Winter, C. C. Rabin et al., Human metapneumovirus SH and G glycoproteins inhibit macropinocytosis-mediated entry into human dendritic cells and reduce CD4(C) T cell activation, J Virol, vol.88, pp.6453-69, 2014.

C. Deffrasnes, M. E. Hamelin, G. A. Prince, and G. Boivin, Identification and evaluation of a highly effective fusion inhibitor for human metapneumovirus, Antimicrob Agents Chemother, vol.52, p.17967906, 2008.


C. E. Palavecino, P. F. Cespedes, R. S. Gomez, A. M. Kalergis, and S. M. Bueno, Immunization with a Recombinant Bacillus Calmette-Guerin Strain Confers Protective Th1 Immunity against the Human Metapneumovirus, J Immunol, vol.192, pp.214-237, 2014.

N. I. Mazur, F. Martinon-torres, E. Baraldi, B. Fauroux, A. Greenough et al., Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics, Lancet Respir Med, vol.3, issue.11, pp.255-261, 2015.

Z. Sun, Q. Wang, R. Jia, S. Xia, Y. Li et al., Intranasal administration of maleic anhydride-modified human serum albumin for preexposure prophylaxis of respiratory syncytial virus infection, Viruses, vol.7, p.25690799, 2015.


J. H. Schickli, D. C. Whitacre, R. S. Tang, J. Kaur, H. Lawlor et al., Palivizumab epitope-displaying virus-like particles protect rodents from RSV challenge, J Clin Invest, vol.125, pp.1637-1684, 2015.

Q. N. Pham, S. Biacchesi, M. H. Skiadopoulos, B. R. Murphy, P. L. Collins et al., Chimeric recombinant human metapneumoviruses with the nucleoprotein or phosphoprotein open reading frame replaced by that of avian metapneumovirus exhibit improved growth in vitro and attenuation in vivo, J Virol, vol.79, p.16306583, 2005.

, , pp.15114-15122, 2005.

M. Gomez, M. A. Mufson, F. Dubovsky, C. Knightly, W. Zeng et al., Phase-I study MEDI-534, of a live, attenuated intranasal vaccine against respiratory syncytial virus and parainfluenza-3 virus in seropositive children, Pediatr Infect Dis J, vol.28, pp.655-663, 2009.

F. M. Munoz, P. A. Piedra, and W. P. Glezen, Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women, Vaccine, vol.21, pp.352-361, 2003.

K. M. Cautivo, S. M. Bueno, C. M. Cortes, A. Wozniak, C. A. Riedel et al., Efficient lung recruitment of respiratory syncytial virus-specific Th1 cells induced by recombinant bacillus Calmette-Guerin promotes virus clearance and protects from infection, J Immunol, vol.185, pp.7633-7678, 2010.

S. M. Bueno, P. A. Gonzalez, K. M. Cautivo, J. E. Mora, E. D. Leiva et al., Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG, Proc Natl Acad Sci U S A, vol.105, pp.20822-20829, 2008.

X. Ma, R. Endo, T. Ebihara, N. Ishiguro, H. Ishiko et al., Production and characterization of neutralizing monoclonal antibodies against human metapneumovirus F protein

, Hybridoma (Larchmt), vol.24, p.16120026, 2005.


A. Mejias, S. Chavez-bueno, A. M. Rios, M. F. Aten, B. Raynor et al., Comparative effects of two neutralizing anti-respiratory syncytial virus (RSV) monoclonal antibodies in the RSV murine model: time versus potency, Antimicrob Agents Chemother, vol.49, p.16251314, 2005.


K. N. Subramanian, L. E. Weisman, T. Rhodes, R. Ariagno, P. J. Sanchez et al., Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group, Pediatr Infect Dis J, vol.17, pp.110-115, 1998.

A. R. Falsey, P. A. Hennessey, M. A. Formica, C. Cox, and E. E. Walsh, Respiratory syncytial virus infection in elderly and high-risk adults, N Engl J Med, vol.352, pp.1749-59, 2005.


A. R. Falsey, H. K. Singh, and E. E. Walsh, Serum antibody decay in adults following natural respiratory syncytial virus infection, J Med Virol, vol.78, p.16998887, 2006.

E. E. Walsh and A. R. Falsey, Humoral and mucosal immunity in protection from natural respiratory syncytial virus infection in adults, J Infect Dis, vol.190, pp.373-381, 2004.

, , p.15216475

M. Vissers, I. M. Ahout, M. I. De-jonge, and G. Ferwerda, Mucosal IgG levels correlate better with respiratory syncytial virus load and inflammation than plasma IgG levels, Clin Vaccine Immunol, vol.23, pp.243-248, 2015.

M. S. Habibi, A. Jozwik, S. Makris, J. Dunning, A. Paras et al., Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus, Am J Respir Crit Care Med, vol.191, pp.1040-1049, 2015.


E. Walsh and A. R. Falsey, Humoral and Mucosal immunity in protection from Natural Respiratory Syncytial virus infection in adults, J Infect Dis, vol.190, pp.373-381, 2004.

, , p.15216475

B. S. Graham, L. A. Bunton, J. Rowland, P. F. Wright, and D. T. Karzon, Respiratory syncytial virus infection in anti-mutreated mice, J Virol, vol.65, p.1908028, 1991.

N. Homaira, W. Rawlinson, T. L. Snelling, and A. Jaffe, Effectiveness of Palivizumab in Preventing RSV hospitalization in high risk children: A real-world perspective, Int J Pediatr, 2014.

L. Lambert, A. M. Sagfors, P. Openshaw, and F. J. Culley, Immunity to RSV in Early-Life, Frontiers Immunol, vol.5, p.466, 2014.

C. J. Sande, M. N. Mutunga, E. A. Okiro, G. F. Medley, P. A. Cane et al., Kinetics of the neutralizing antibody response to respiratory syncytial virus infections in a birth cohort, J Medical Virol, vol.85, pp.2020-2025, 2013.


D. H. Schuurhuis, A. Ioan-facsinay, B. Nagelkerken, J. J. Van-schip, C. Sedlik et al., Antigen-antibody immune complexes empower dendritic cells to efficiently prime specific CD8 C CTL responses in vivo, J Immunol, vol.168, p.11859111, 2002.


D. Kruijsen, M. J. Bakkers, N. O. Van-uden, M. C. Viveen, T. C. Van-der-sluis et al., Serum antibodies critically affect virus-specific CD4

. C-/cd8,

, C T cell balance during respiratory syncytial virus infections, J Immunol, vol.185, pp.6489-98, 2010.


D. Kruijsen, H. K. Einarsdottir, M. A. Schijf, F. E. Coenjaerts, E. C. Van-der-schoot et al., Intranasal administration of antibody-bound respiratory syncytial virus particles efficiently primes virus-specific immune responses in mice, J Virol, vol.87, pp.7550-7557, 2013.


F. P. Polack, M. N. Teng, P. L. Collins, G. A. Prince, M. Exner et al., A role for immune complexes in enhanced respiratory syncytial virus disease, The J Exp Med, vol.196, pp.859-65, 2002.

I. Rossey, K. Sedeyn, D. Baets, and S. ,

, C T cell immunity against human respiratory syncytial virus, Vaccine, vol.32, p.25223272, 2014.


A. F. Christiaansen, C. J. Knudson, K. A. Weiss, and S. M. Varga, The CD4 T cell response to respiratory syncytial virus infection, Immunol Res, vol.59, pp.109-126, 2014.

A. Jozwik, M. S. Habibi, A. Paras, J. Zhu, A. Guvenel et al., RSVspecific airway resident memory CD8

, C T cells and differential disease severity after experimental human infection, Nat Commun, vol.6, 2015.

C. B. Hall, K. R. Powell, N. E. Macdonald, C. L. Gala, M. E. Menegus et al., Respiratory syncytial viral infection in children with compromised immune function, N Engl J Med, vol.315, p.3724802, 1986.


M. J. Cannon, E. J. Stott, G. Taylor, and B. A. Askonas, Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells, Immunology, vol.62, p.3498683, 1987.

B. Bagga, J. E. Cehelsky, A. Vaishnaw, T. Wilkinson, R. Meyers et al., Effect of preexisting serum and mucosal antibody on experimental Respiratory Syncytial Virus (RSV) challenge and infection of adults, J Infect Dis, vol.212, pp.1719-1744, 2015.

X. Jiang, R. A. Clark, L. Liu, A. J. Wagers, R. C. Fuhlbrigge et al., Skin infection generates non-migratory memory CD8

C. , RM) cells providing global skin immunity, Nature, vol.483, p.22388819, 2012.


J. M. Schenkel, K. A. Fraser, V. Vezys, and D. Masopust, Sensing and alarm function of resident memory CD8(C) T cells, Nat Immunol, vol.14, p.23542740, 2013.


C. M. Oshansky, W. Zhang, E. Moore, and R. A. Tripp, The host response and molecular pathogenesis associated with respiratory syncytial virus infection, Future Microbiol, vol.4, pp.279-97, 2009.

G. J. De-bree, E. M. Van-leeuwen, T. A. Out, H. M. Jansen, R. E. Jonkers et al., Selective accumulation of differentiated CD8

, C T cells specific for respiratory viruses in the human lung, J Exp Med, vol.202, pp.1433-1475, 2005.


T. Ostler, W. Davidson, and S. Ehl, Virus clearance and immunopathology by CD8(C) T cells during infection with respiratory syncytial virus are mediated by IFNgamma, Eur J Immunol, vol.32, pp.2117-2140, 2002.

, , vol.32, 200208.

M. J. Cannon, P. J. Openshaw, and B. A. Askonas, Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus, J Exp Med, vol.168, pp.1163-1171, 1988.

M. L. Everard, A. Swarbrick, M. Wrightham, J. Mcintyre, C. Dunkley et al., Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection, Arch Dis Child, vol.71, pp.428-460, 1994.

P. S. Mcnamara, P. Ritson, A. Selby, C. A. Hart, and R. L. Smyth, Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis, Arch Dis Child, vol.88, pp.922-928, 2003.

T. P. Welliver, R. P. Garofalo, Y. Hosakote, K. H. Hintz, L. Avendano et al., Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses, J Infect Dis, vol.195, pp.1126-1162, 2007.

Y. M. Hosakote, P. D. Jantzi, D. L. Esham, H. Spratt, A. Kurosky et al., Viral-mediated inhibition of antioxidant enzymes contributes to the pathogenesis of severe respiratory syncytial virus bronchiolitis, Am J Respir Crit Care Med, vol.183, pp.1550-60, 2011.

, , pp.201010-1755

G. A. Funchal, N. Jaeger, R. S. Czepielewski, M. S. Machado, S. P. Muraro et al., Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils, PLoS One, vol.10, 2015.

C. M. El-saleeby, J. Suzich, M. E. Conley, and J. P. Devincenzo, Quantitative effects of palivizumab and donorderived T cells on chronic respiratory syncytial virus infection, lung disease, and fusion glycoprotein amino acid sequences in a patient before and after bone marrow transplantation, Clin Infect Dis, vol.39, pp.17-20, 2004.

M. Roman, W. J. Calhoun, K. L. Hinton, L. F. Avendano, V. Simon et al., Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response, Am J Respir Crit Care Med, vol.156, pp.190-195, 1997.

J. F. Bermejo-martin, G. Mc, D. Lejarazu, R. O. Ardura, J. Eiros et al., Predominance of Th2 cytokines, CXC chemokines and innate immunity mediators at the mucosal level during severe respiratory syncytial virus infection in children, Eur Cytokine Netw, vol.18, p.17823085, 2007.

J. H. Aberle, S. W. Aberle, M. N. Dworzak, C. W. Mandl, W. Rebhandl et al., Reduced interferon-gamma expression in peripheral blood mononuclear cells of infants with severe respiratory syncytial virus disease, Am J Respir Crit Care Med, vol.160, pp.1263-1271, 1999.

R. Y. Sung, S. H. Hui, C. K. Wong, C. W. Lam, and J. Yin, A comparison of cytokine responses in respiratory syncytial virus and influenza A infections in infants, Eur J Pediatr, vol.160, pp.117-139, 2001.

P. S. Mcnamara, B. F. Flanagan, A. M. Selby, C. A. Hart, and R. L. Smyth, Pro-and anti-inflammatory responses in respiratory syncytial virus bronchiolitis, Eur Respir J, vol.23, pp.106-118, 2004.

H. C. Lee, M. B. Headley, Y. M. Loo, A. Berlin, M. Gale et al., Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection, J Allergy Clin Immunol, vol.130, pp.1187-96, 2012.


N. W. Lukacs, K. K. Tekkanat, A. Berlin, C. M. Hogaboam, A. Miller et al., Respiratory syncytial virus predisposes mice to augmented allergic airway responses via IL-13-mediated mechanisms, J Immunol, vol.167, pp.1060-1065, 2001.

T. Rothoeft, K. Fischer, S. Zawatzki, V. Schulz, U. Schauer et al., Differential response of human naive and memory/effector T cells to dendritic cells infected by respiratory syncytial virus, Clin Exp Immunol, vol.150, pp.263-73, 2007.

R. He and R. S. Geha, Thymic stromal lymphopoietin, Ann N Y Acad Sci, vol.1183, pp.13-24, 2010.

V. Soumelis, P. A. Reche, H. Kanzler, W. Yuan, G. Edward et al., Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP, Nat Immunol, vol.3, pp.673-80, 2002.

J. Qiao, A. Li, and J. X. , TSLP from RSV-stimulated rat airway epithelial cells activates myeloid dendritic cells, Immunol Cell Biol, vol.89, pp.231-239, 2011.


T. Ito, Y. H. Wang, O. Duramad, T. Hori, G. J. Delespesse et al., TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand, J Exp Med, vol.202, pp.1213-1236, 2005.

D. You, N. Marr, J. Saravia, B. Shrestha, G. I. Lee et al.,

, C T cells plays a pathogenic role in respiratory syncytial virus reinfection in mice infected initially as neonates, J Leukoc Biol, vol.93, pp.933-975, 2013.

, , p.23543769

B. S. Graham, L. A. Bunton, P. F. Wright, and D. T. Karzon, Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice, J Clin Invest, vol.88, pp.1026-1059, 1991.

, PMID, 1909350.

A. Cherukuri, K. Patton, R. A. Gasser, . Jr, F. Zuo et al., Adults 65 years old and older have reduced numbers of functional memory T cells to respiratory syncytial virus fusion protein, Clin Vaccine Immunol, vol.20, pp.239-286, 2013.

P. J. Openshaw and C. Chiu, Protective and dysregulated T cell immunity in RSV infection, Curr Opin Virol, vol.3, pp.468-74, 2013.

B. C. Petersen, V. Dolgachev, A. Rasky, and N. W. Lukacs, IL-17E (IL-25) and IL-17RB promote respiratory syncytial virus-induced pulmonary disease, J Leukoc Biol, 2014.

, , vol.95, pp.809-815

S. Mukherjee, D. M. Lindell, A. A. Berlin, S. B. Morris, T. P. Shanley et al., IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease, Am J Pathol, vol.179, pp.248-58, 2011.

L. Qin, C. P. Hu, J. T. Feng, and Q. Xia, Activation of lymphocytes induced by bronchial epithelial cells with prolonged RSV infection, PLoS One, vol.6, p.22216085, 2011.


T. Chirkova, S. Boyoglu-barnum, K. A. Gaston, F. M. Malik, S. P. Trau et al., Respiratory syncytial virus G protein CX3C motif impairs human airway epithelial and immune cell responses, J Virol, vol.87, pp.13466-79, 2013.

T. E. Faber, H. Groen, M. Welfing, K. J. Jansen, and L. J. Bont, Specific increase in local IL-17 production during recovery from primary RSV bronchiolitis, J Med Virol, vol.84, pp.1084-1092, 2012.

K. L. Stokes, M. G. Currier, K. Sakamoto, S. Lee, P. L. Collins et al., The respiratory syncytial virus fusion protein and neutrophils mediate the airway mucin response to pathogenic respiratory syncytial virus infection, J Virol, vol.87, pp.10070-82, 2013.

M. Gengs, . Okamotot, . Yaoy, . Lur, . Pagek et al., Emergence, origin, and function of neutrophil-dendritic cell hybrids in experimentally induced inflammatory lesions in mice, Blood, vol.121, 2013.

H. Matsushima, S. Geng, R. Lu, T. Okamoto, Y. Yao et al., Neutrophil differentiation into a unique hybrid population exhibiting dual phenotype and functionality of neutrophils and dendritic cells, Blood, vol.121, pp.1677-89, 2013.

C. P. Halfhide, B. F. Flanagan, S. P. Brearey, J. A. Hunt, A. M. Fonceca et al., Respiratory syncytial virus binds and undergoes transcription in neutrophils from the blood and airways of infants with severe bronchiolitis, J Infect Dis, vol.204, pp.451-459, 2011.

A. B. Kulkarni, H. C. Morse, J. R. Bennink, J. W. Yewdell, and B. R. Murphy, Immunization of mice with vaccinia virus-M2 recombinant induces epitope-specific and cross-reactive Kd-restricted CD8

C. Cells, J Virol, vol.67, p.7685408, 1993.

C. Bartholdy, W. Olszewska, A. Stryhn, A. R. Thomsen, and P. J. Openshaw, Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced pneumonitis, J Gen Virol, vol.85, pp.3017-3043, 2004.

C. P. Simmons, T. Hussell, T. Sparer, G. Walzl, P. Openshaw et al., Mucosal delivery of a respiratory syncytial virus CTL peptide with enterotoxin-based adjuvants elicits protective, immunopathogenic, and immunoregulatory antiviral CD8

C. , J Immunol, vol.166, pp.1106-1119, 2001.

T. J. Ruckwardt, C. Luongo, A. M. Malloy, J. Liu, M. Chen et al., Responses against a subdominant CD8

, C T cell epitope protect against immunopathology caused by a dominant epitope, J Immunol, vol.185, pp.4673-80, 2010.

J. Liu, E. K. Haddad, J. Marceau, K. M. Morabito, S. S. Rao et al., A Numerically Subdominant CD8 T Cell response to matrix protein of respiratory syncytial virus controls infection with limited immunopathology, PLoS Pathog, vol.12, 2016.

D. Baets, S. Schepens, B. Sedeyn, K. Schotsaert, M. Roose et al., Recombinant influenza virus carrying the respiratory syncytial virus (RSV) F85-93 CTL epitope reduces RSV replication in mice, J Virol, vol.87, pp.3314-3337, 2013.

M. Venter, M. Rock, A. J. Puren, C. T. Tiemessen, J. E. Crowe et al., Respiratory syncytial virus nucleoprotein-specific cytotoxic T-cell epitopes in a South African population of diverse HLA types are conserved in circulating field strains, J Virol, vol.77, p.12805430, 2003.


J. Heidema, G. J. De-bree, D. Graaff, P. M. Van-maren, W. W. Hoogerhout et al., Human CD8(C) T cell responses against five newly identified respiratory syncytial virus-derived epitopes, J Gen Virol, vol.85, pp.2365-74, 2004.

A. G. Telcian, V. Laza-stanca, M. R. Edwards, J. A. Harker, H. Wang et al., RSV-induced bronchial epithelial cell PD-L1 expression inhibits CD8

, C T cell nonspecific antiviral activity, J Infect Dis, vol.203, pp.85-94, 2011.


T. Hussell and P. J. Openshaw, Intracellular IFN-gamma expression in natural killer cells precedes lung CD8 C T cell recruitment during respiratory syncytial virus infection, J Gen Virol, vol.79, pp.2593-601, 1998.


M. Q. Ge, A. W. Ho, Y. Tang, K. H. Wong, B. Y. Chua et al., NK cells regulate CD8

, C T cell priming and dendritic cell migration during influenza A infection by IFN-gamma and perforin-dependent mechanisms, J Immunol, vol.189, p.22869906, 2012.


M. V. Lukens, A. C. Van-de-pol, F. E. Coenjaerts, N. J. Jansen, V. M. Kamp et al., A systemic neutrophil response precedes robust CD8(C) T-cell activation during natural respiratory syncytial virus infection in infants, J Virol, vol.84, pp.2374-83, 2010.

R. Fearns and P. L. Collins, Role of the M2-1 transcription antitermination protein of respiratory syncytial virus in sequential transcription, J Virol, vol.73, pp.5852-64, 1999.

H. Jin, X. Cheng, H. Z. Zhou, S. Li, and A. Seddiqui, Respiratory syncytial virus that lacks open reading frame 2 of the M2 gene (M2-2) has altered growth characteristics and is attenuated in rodents, J Virol, vol.74, pp.74-82, 2000.

, , p.10590093

J. S. Mclellan, W. C. Ray, and M. E. Peeples, Structure and function of respiratory syncytial virus surface glycoproteins, Curr Top Microbiol Immunol, vol.372, pp.83-104, 2013.

A. Bukreyev, L. Yang, J. Fricke, L. Cheng, J. M. Ward et al., The secreted form of respiratory syncytial virus G glycoprotein helps the virus evade antibody-mediated restriction of replication by acting as an antigen decoy and through effects on Fc receptor-bearing leukocytes, J Virol, vol.82, pp.12191-204, 2008.

J. Harcourt, R. Alvarez, L. P. Jones, C. Henderson, L. J. Anderson et al., Respiratory syncytial virus G protein and G protein CX3C motif adversely affect CX3CR1C T cell responses, J Immunol, vol.176, p.16424189, 2006.


J. Schlender, G. Walliser, J. Fricke, and K. K. Conzelmann, Respiratory syncytial virus fusion protein mediates inhibition of mitogen-induced T-cell proliferation by contact, J Virol, vol.76, 2002.

S. W. Gan, E. Tan, X. Lin, D. Yu, J. Wang et al., The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels, J Biol Chem, vol.287, pp.24671-89, 2012.

S. Fuentes, K. C. Tran, P. Luthra, M. N. Teng, and B. He, Function of the respiratory syncytial virus small hydrophobic protein, J Virol, vol.81, p.17494063, 2007.


R. A. Tripp, D. Moore, L. Jones, W. Sullender, J. Winter et al., Respiratory syncytial virus G and/or SH protein alters Th1 cytokines, natural killer cells, and neutrophils responding to pulmonary infection in BALB/c mice, J Virol, vol.73, pp.7099-107, 1999.

K. M. Spann, K. C. Tran, and P. L. Collins, Effects of nonstructural proteins NS1 and NS2 of human respiratory syncytial virus on interferon regulatory factor 3, NFkappaB, and proinflammatory cytokines, J Virol, vol.79, pp.5353-5362, 2005.

S. Barik, Respiratory syncytial virus mechanisms to interfere with type 1 interferons, Curr Top Microbiol Immunol, vol.372, p.24362690, 2013.
DOI : 10.1007/978-3-642-38919-1_9

J. Elliott, O. T. Lynch, Y. Suessmuth, P. Qian, C. R. Boyd et al., Respiratory syncytial virus NS1 protein degrades STAT2 by using the Elongin-Cullin E3 ligase, J Virol, vol.81, pp.3428-3464, 2007.

R. M. Liesman, U. J. Buchholz, C. L. Luongo, L. Yang, A. D. Proia et al., RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction, J Clin Invest, vol.124, pp.2219-2252, 2014.
DOI : 10.1172/jci72948

URL : http://www.jci.org/articles/view/72948/files/pdf


S. Munir, L. Nouen, C. Luongo, C. Buchholz, U. J. Collins et al., Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells, J Virol, vol.82, pp.8780-96, 2008.

S. Munir, P. Hillyer, L. Nouen, C. Buchholz, U. J. Rabin et al., Respiratory syncytial virus interferon antagonist NS1 protein suppresses and skews the human T lymphocyte response, PLoS Pathog, vol.7, 2011.

A. Kotelkin, I. M. Belyakov, L. Yang, J. A. Berzofsky, P. L. Collins et al., The NS2 protein of human respiratory syncytial virus suppresses the cytotoxic T-cell response as a consequence of suppressing the type I interferon response, J Virol, vol.80, p.16731934, 2006.


K. Reimers, K. Buchholz, and H. Werchau, Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B, Virology, vol.331, p.15629770, 2005.


S. E. Bakker, S. Duquerroy, M. Galloux, C. Loney, E. Conner et al., The respiratory syncytial virus nucleoprotein-RNA complex forms a left-handed helical nucleocapsid, J Gen Virol, 2013.

, , vol.94, pp.1734-1742

A. W. Lifland, J. Jung, E. Alonas, C. Zurla, J. E. Crowe et al., Human respiratory syncytial virus nucleoprotein and inclusion bodies antagonize the innate immune response mediated by MDA5 and MAVS, J Virol, vol.86, pp.8245-58, 2012.

P. F. Cespedes, S. M. Bueno, B. A. Ramirez, R. S. Gomez, S. A. Riquelme et al., Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells, Proc Natl Acad Sci U S A, vol.111, pp.3214-3237, 2014.

N. Osman, S. Lucas, and D. Cantrell, The role of tyrosine phosphorylation in the interaction of cellular tyrosine kinases with the T cell receptor zeta chain tyrosine-based activation motif, Eur J Immunol, vol.25, pp.2863-2872, 1995.


J. Leung, F. Esper, C. Weibel, and J. S. Kahn, Seroepidemiology of human metapneumovirus (hMPV) on the basis of a novel enzyme-linked immunosorbent assay utilizing hMPV fusion protein expressed in recombinant vesicular stomatitis virus, J Clin Microbiol, vol.43, pp.1213-1222, 2005.

, , pp.1213-1219, 2005.

A. R. Falsey, P. A. Hennessey, M. A. Formica, M. M. Criddle, J. M. Biear et al., Humoral immunity to human metapneumovirus infection in adults, Vaccine, vol.28, pp.1477-80, 2010.

R. Alvarez and R. A. Tripp, The immune response to human metapneumovirus is associated with aberrant immunity and impaired virus clearance in BALB/c mice, J Virol, vol.79, pp.5971-5979, 2005.

R. Alvarez, K. S. Harrod, W. J. Shieh, S. Zaki, and R. A. Tripp, Human metapneumovirus persists in BALB/c mice despite the presence of neutralizing antibodies, J Virol, vol.78, pp.14003-14014, 2004.

M. Debiaggi, F. Canducci, M. Sampaolo, M. C. Marinozzi, M. Parea et al., Persistent symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients, J Infect Dis, vol.194, pp.474-482, 2006.

Y. Abed and G. Boivin, Human metapneumovirus infection in immunocompromised child, Emerg Infect Dis, vol.14, pp.854-860, 2008.

K. A. Herd, M. Nelson, S. Mahalingam, and R. W. Tindle, Pulmonary infection of mice with human metapneumovirus induces local cytotoxic T-cell and immunoregulatory cytokine responses similar to those seen with human respiratory syncytial virus, J Gen Virol, vol.91, pp.1302-1312, 2010.

D. Kolli, E. L. Bataki, L. Spetch, A. Guerrero-plata, A. M. Jewell et al., T lymphocytes contribute to antiviral immunity and pathogenesis in experimental human metapneumovirus infection, J Virol, vol.82, p.18562525, 2008.


M. K. Lay, P. F. Cespedes, C. E. Palavecino, M. A. Leon, R. A. Diaz et al., Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice, Eur J Immunol, vol.45, issue.6, pp.1680-95, 2015.
URL : https://hal.archives-ouvertes.fr/inserm-02146519

K. A. Herd, M. D. Nissen, P. M. Hopkins, T. P. Sloots, and R. W. Tindle, Major histocompatibility complex class I cytotoxic T lymphocyte immunity to human metapneumovirus (hMPV) in individuals with previous hMPV infection and respiratory disease, J Infect Dis, vol.197, pp.584-92, 2008.

, , p.18240952

S. Diehl and M. Rincon, The two faces of IL-6 on Th1/Th2 differentiation, Mol Immunol, vol.39, pp.531-537, 2002.

, , pp.210-219

R. N. Douville, N. Bastien, Y. Li, P. Pochard, F. E. Simons et al., Human metapneumovirus elicits weak IFN-gamma memory responses compared with respiratory syncytial virus, J Immunol, vol.176, pp.5848-55, 2006.


F. R. Laham, V. Israele, J. M. Casellas, A. M. Garcia, L. Prugent et al., Differential production of inflammatory cytokines in primary infection with human metapneumovirus and with other common respiratory viruses of infancy, J Infect Dis, vol.189, pp.2047-56, 2004.

L. Nouen, C. Hillyer, P. Brock, L. G. Winter, C. C. Rabin et al., Human metapneumovirus SH and G glycoproteins inhibit macropinocytosis-mediated entry into human dendritic cells and reduce CD4

, C T cell activation, J Virol, vol.88, p.24672038, 2014.


A. Guerrero-plata, A. Casola, G. Suarez, X. Yu, L. Spetch et al., Differential response of dendritic cells to human metapneumovirus and respiratory syncytial virus, Am J Respir Cell Mol Biol, vol.34, pp.320-329, 2006.

L. Nouen, C. Hillyer, P. Munir, S. Winter, C. C. Mccarty et al., Effects of human respiratory syncytial virus, metapneumovirus, parainfluenza virus 3 and influenza virus on CD4 C T cell activation by dendritic cells, PLoS One, vol.5, p.21124776, 2010.


S. C. Wen, J. E. Schuster, P. Gilchuk, K. L. Boyd, S. Joyce et al., Lung, vol.8

, C T cell impairment occurs during human metapneumovirus infection despite virus-like particle (VLP) induction of functional CD8 C T cells, J Virol, vol.89, issue.17, pp.8713-8739, 2015.

G. A. Melendi, F. Zavala, U. J. Buchholz, G. Boivin, P. L. Collins et al., Mapping and characterization of the primary and anamnestic H-2(d)-restricted cytotoxic T-lymphocyte response in mice against human metapneumovirus, J Virol, vol.81, p.17670840, 2007.


A. K. Hastings, J. J. Erickson, J. E. Schuster, K. L. Boyd, S. J. Tollefson et al., Role of type I interferon signaling in human metapneumovirus pathogenesis and control of viral replication, J Virol, vol.89, pp.4405-4425, 2015.

J. J. Erickson, P. Gilchuk, A. K. Hastings, S. J. Tollefson, M. Johnson et al.,

S. Joyce, Viral acute lower respiratory infections impair CD8

, C T cells through PD-1, J Clin Invest, 2012.

, , vol.122, pp.2967-82

J. J. Erickson, M. C. Rogers, A. K. Hastings, S. J. Tollefson, and J. V. Williams, Programmed death-1 impairs secondary effector lung CD8(C) T cells during respiratory virus reinfection, J Immunol, vol.193, pp.5108-5125, 2014.

C. Deffrasnes, M. E. Hamelin, and G. Boivin, Human metapneumovirus, Semin Respir Crit Care Med, vol.28, pp.213-234, 2007.

N. Ishiguro, T. Ebihara, R. Endo, X. Ma, H. Kikuta et al., High genetic diversity of the attachment (G) protein of human metapneumovirus, J Clin Microbiol, vol.42, pp.3406-3420, 2004.

X. Bao, T. Liu, Y. Shan, K. Li, R. P. Garofalo et al., Human metapneumovirus glycoprotein G inhibits innate immune responses, PLoS Pathog, vol.4, 2008.

X. Bao, D. Kolli, T. Liu, Y. Shan, R. P. Garofalo et al., Human metapneumovirus small hydrophobic protein inhibits NF-kappaB transcriptional activity, J Virol, vol.82, pp.8224-8233, 2008.

T. Takimoto and A. Portner, Molecular mechanism of paramyxovirus budding, Virus Res, vol.106, pp.133-178, 2004.


A. Bagnaud-baule, R. O. Perret, M. Berland, J. L. Maache, M. Peyrefitte et al., The human metapneumovirus matrix protein stimulates the inflammatory immune response in vitro, PLoS One, vol.6, p.21412439, 2011.


H. Cai, Y. Zhang, Y. Ma, J. Sun, X. Liang et al., Zinc binding activity of human metapneumovirus M2-1 protein is indispensable for viral replication and pathogenesis in vivo, J Virol, vol.89, pp.6391-405, 2015.


U. J. Buchholz, S. Biacchesi, Q. N. Pham, K. C. Tran, L. Yang et al., Deletion of M2 gene open reading frames 1 and 2 of human metapneumovirus: effects on RNA synthesis, attenuation, and immunogenicity, J Virol, vol.79, pp.6588-97, 2005.

Y. Kitagawa, M. Zhou, M. Yamaguchi, T. Komatsu, K. Takeuchi et al., Human metapneumovirus M2-2 protein inhibits viral transcription and replication, Microbes Infect, vol.12, pp.135-180, 2010.


J. Ren, Q. Wang, D. Kolli, D. J. Prusak, C. T. Tseng et al., Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS, J Virol, vol.86, p.23015697, 2012.


A. Busche, A. C. Jirmo, S. P. Welten, J. Zischke, J. Noack et al., , p.8

, C T cells against cytomegalovirus-encoded antigens is dominated by cross-presentation, J Immunol, vol.190, p.23390296, 2013.


R. G. Cox, J. J. Erickson, A. K. Hastings, J. C. Becker, M. Johnson et al., Human metapneumovirus virus-like particles induce protective B and T cell responses in a mouse model, J Virol, vol.88, pp.6368-79, 2014.

R. Singleton, N. Etchart, S. Hou, and L. Hyland, Inability to evoke a long-lasting protective immune response to respiratory syncytial virus infection in mice correlates with ineffective nasal antibody responses, J Virol, vol.77, pp.11303-11314, 2003.

T. Hussell, L. C. Spender, A. Georgiou, A. O'garra, and P. J. Openshaw, Th1 and Th2 cytokine induction in pulmonary T cells during infection with respiratory syncytial virus, J Gen Virol, vol.77, p.8887477, 1996.