title: Tobacco mosaic virus in the lungs of mice following intra-tracheal inoculation.
abstract: Plant viruses are generally considered incapable of infecting vertebrates. Accordingly, they are not considered harmful for humans. However, a few studies questioned the certainty of this paradigm. Tobacco mosaic virus (TMV) RNA has been detected in human samples and TMV RNA translation has been described in animal cells. We sought to determine if TMV is detectable, persists, and remains viable in the lung tissues of mice following intratracheal inoculation, and we attempted to inoculate mouse macrophages with TMV. In the animal model, mice were intratracheally inoculated with 10(11) viral particles and were sacrificed at different time points. The virus was detected in the mouse lungs using immunohistochemistry, electron microscopy, real-time RT-PCR and sequencing, and its viability was studied with an infectivity assay on plants. In the cellular model, the culture medium of murine bone marrow derived macrophages (BMDM) was inoculated with different concentrations of TMV, and the virus was detected with real-time RT-PCR and immunofluorescence. In addition, anti-TMV antibodies were detected in mouse sera with ELISA. We showed that infectious TMV could enter and persist in mouse lungs via the intratracheal route. Over 14 days, the TMV RNA level decreased by 5 log(10) copies/ml in the mouse lungs and by 3.5 log(10) in macrophages recovered from bronchoalveolar lavage. TMV was localized to lung tissue, and its infectivity was observed on plants until 3 days after inoculation. In addition, anti-TMV antibody seroconversions were observed in the sera from mice 7 days after inoculation. In the cellular model, we observed that TMV persisted over 15 days after inoculation and it was visualized in the cytoplasm of the BMDM. This work shows that a plant virus, Tobacco mosaic virus, could persist and enter in cells in mammals, which raises questions about the potential interactions between TMV and human hosts.
authors: Aix-Marseille Univ., Unité de Recherche sur les Maladies Infectieuses et Tropicales Émergentes (URMITE) UM 63 CNRS 7278 IRD 3R198 INSERM U1095, IHU Méditerranée Infection, Facultés de Médecine et de Pharmacie, Marseille, France.
authors: Fanny
authors: F
authors: Balique
authors: Philippe
authors: P
authors: Colson
authors: Abdoulaye Oury
authors: AO
authors: Barry
authors: Claude
authors: C
authors: Nappez
authors: Audrey
authors: A
authors: Ferretti
authors: Khatoun Al
authors: KA
authors: Moussawi
authors: Tatsiana
authors: T
authors: Ngounga
authors: Hubert
authors: H
authors: Lepidi
authors: Eric
authors: E
authors: Ghigo
authors: Jean-Louis
authors: JL
authors: Mege
authors: Hervé
authors: H
authors: Lecoq
authors: Didier
authors: D
authors: Raoult
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D008168:Lung / Q000821:virology*; D008264:Macrophages / Q000166:cytology / Q000821:virology; D051379:Mice; D050296:Microbial Viability; D012698:Serologic Tests; D014027:Tobacco Mosaic Virus / Q000276:immunology / Q000502:physiology*; D014132:Trachea / Q000821:virology*
chemical_list: D000914:Antibodies, Viral
references: Virus Res. 2009 May;141(2):113-30
references: 19159652
references: J Clin Microbiol. 1998 Oct;36(10):3028-31
references: 9738061
references: Naturwissenschaften. 1975 Nov;62(11):533
references: 814472
references: Nucleic Acids Res. 1975 Oct;2(10):1719-26
references: 1187342
references: J Gen Virol. 1993 Mar;74 ( Pt 3):341-9
references: 8445364
references: PLoS One. 2010 Apr 06;5(4):e10041
references: 20386604
references: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):10757-8
references: 17581867
references: Genetics. 1974 Sep;78(1):383-94
references: 4474972
references: Mol Plant Pathol. 2011 Dec;12(9):938-54
references: 22017770
references: J Clin Virol. 2012 Dec;55(4):374-6
references: 22959216
references: J Immunol. 1957 Feb;78(2):95-103
references: 13429072
references: Plant Cell. 2004 May;16(5):1235-50
references: 15084715
references: Vaccine. 2000 Apr 28;18(21):2266-74
references: 10717347
references: Clin Diagn Lab Immunol. 2004 Jan;11(1):42-9
references: 14715543
references: PLoS Biol. 2006 Jan;4(1):e3
references: 16336043
references: Intervirology. 1983;19(3):129-34
references: 6832939
references: J Virol. 2004 May;78(10):4976-82
references: 15113877
references: J Immunol. 1953 Jul;71(1):30-7
references: 13069723
references: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):10986-91
references: 17573530
references: Infect Immun. 1997 Jun;65(6):2443-7
references: 9169787
references: PLoS Pathog. 2009 May;5(5):e1000417
references: 19412526
references: PLoS One. 2010 Jun 24;5(6):e11298
references: 20585574
references: Virology. 2005 Dec 20;343(2):224-35
references: 16185741
references: J Biosci Bioeng. 2006 May;101(5):398-402
references: 16781468
references: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12157-62
references: 17615233
references: Bioconjug Chem. 2006 Sep-Oct;17(5):1330-8
references: 16984144
references: J Gen Virol. 1997 Oct;78 ( Pt 10):2683-9
references: 9349491
references: Vaccine. 2005 Mar 7;23(15):1875-80
references: 15734059
references: PLoS One. 2009;4(1):e4219
references: 19156205
references: Am Rev Respir Dis. 1967 Mar;95(3):510-1
references: 6018711
references: PLoS One. 2010 Jul 22;5(7):e11713
references: 20676356
references: J Virol. 1999 Feb;73(2):930-8
references: 9882293
references: Annu Rev Med. 2009;60:167-79
references: 19630570
references: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2481-5
references: 9482911
references: Med Hypotheses. 2004;63(5):773-7
references: 15488645
references: Arch Virol. 2009;154(12):1967-72
references: 19862474
references: Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1175-80
references: 15657123
references: J Gen Virol. 1982 Oct;62 (Pt 2):343-7
references: 7142974
references: J Virol. 2007 Oct;81(19):10379-88
references: 17634237
references: Philos Trans R Soc Lond B Biol Sci. 1999 Mar 29;354(1383):521-9
references: 10212931
references: Biosci Rep. 2012 Apr 1;32(2):171-86
references: 21729006