In vitro Pneumovirus and Paramixovirus infection is modulated by the passage of mesenchymal stem cells

Volume 7, Issue 3, June 2022     |     PP. 167-179      |     PDF (660 K)    |     Pub. Date: May 3, 2022
DOI: 10.54647/cm32819    71 Downloads     3525 Views  

Author(s)

Karla Zarate, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), CP 04510, Mexico City, Mexico
Xóchitl Ambriz, BioLabs NTX 3033 Irving Blvd, Dallas TX 75247, USA
Javier R. Ambrosio, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), CP 04510, Mexico City, Mexico
Rocio Tirado, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), CP 04510, Mexico City, Mexico

Abstract
The human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV), and the human parainfluenza virus (hPIV) are the main etiological agents of acute respiratory infections in children and adults. Human mesenchymal stem cells (hMSCs) are also infected by these viruses. These cells differentially express receptors according to the number of passages, thereby, influencing susceptibility and permissiveness to viral infections. The aim of this study was to determine the susceptibility of amniotic hMSC to hRSV, hMPV, and hPIV. We examined the effect of hMSC passages on the viral gene expression by endpoint RT-PCR and the viral production by TCID50 and evaluated the effect on the hMSC cytoskeleton by light microscopy. We found that the viral titer increased with respect to the number of hMSC passages. This coincided with the highest gene expression levels documented at the same passages. As for the hMSC morphological changes, we suggest that these changes were associated with actin modifications. Taken together, viral infections of hMSCs cause altered gene expression and cytoskeleton morphology, with the viral loads ascending as a function of the number of passages.

Keywords
Mesenchymal stem cells; human respiratory viral infection; hRSV; hMPV; hPIV; cytoskeleton; susceptibility; permissiveness.

Cite this paper
Karla Zarate, Xóchitl Ambriz, Javier R. Ambrosio, Rocio Tirado, In vitro Pneumovirus and Paramixovirus infection is modulated by the passage of mesenchymal stem cells , SCIREA Journal of Clinical Medicine. Volume 7, Issue 3, June 2022 | PP. 167-179. 10.54647/cm32819

References

[ 1 ] Wu, M., Han, Z.B., Liu, J.F., Wang, Y.W., Zhang, J.Z., Li, C.T., Xin, P. L., Han, Z. C., Zhu, X. P. Serum-Free Media and the Immunoregulatory Properties of Mesenchymal Stem Cells In Vivo and In Vitro. Cell. Physiol. Biochem. 2014, 33(3), 569–580.
[ 2 ] Naji, A., Eitoku, M., Favier, B., Deschaseaux, F., Rouas-Freiss, N., Suganuma, N. Biological functions of mesenchymal stem cells and clinical implications. Cell. Mol. Life Sc 2019, 76(17), 3323–3348.
[ 3 ] Taechangam, N., Kol, A., Arzi, B., Borjesson, D.L. Multipotent Stromal Cells and Viral Interaction: Current Implications for Therapy. Stem Cell Rev. Rep. 2021, 18(1), 214–227.
[ 4 ] Docheva, D., Haasters, F., Schieker, M. Mesenchymal Stem Cells and Their Cell Surface Receptors. Curr. Rheumatol. Rev. 2008, 4(3), 155–160.
[ 5 ] Dimitrov, D.S. Virus entry: molecular mechanisms and biomedical applications. Nat. Rev. Microbiol. 2004, 2(2), 109–122.
[ 6 ] Avanzi, S., Leoni, V., Rotola, A., Alviano, F., Solimando, L., Lanzoni, G., Bonsi, L., di Luca, D., Marchionni, C., Alvisi, G., Ripalti, A. Susceptibility of human placenta derived mesenchymal stromal/stem cells to human herpesviruses infection. PLoS One 2013, 8(8), e71412.
[ 7 ] Behzadi Fard, M., Kaviani, S., Atashi, A. Parvovirus B19 infection in human bone marrow mesenchymal stem cells affects gene expression of IL-6 and TNF-α and also affects hematopoietic stem cells differentiation. Indian J. Hematol. Blood Transfus. 2019, 35(4), 765–772.
[ 8 ] Arzi, B., Kol, A., Murphy, B., Walker, N.J., Wood, J.A., Clark, K., Verstraete, F.J., Borjesson, D. L. Feline foamy virus adversely affects feline mesenchymal stem cell culture and expansion: Implications for animal model development. Stem Cell. Develop. 2015, 24(7), 814–823.
[ 9 ] Cheung, M.B., Sampayo-Escobar, V., Green, R., Moore, M.L., Mohapatra, S., Mohapatra, S.S. Respiratory syncytial virus-infected mesenchymal stem cells regulate immunity via interferon beta and indoleamine-2,3-dioxygenase. PLoS One 2016, 11(10), e0163709.
[ 10 ] Claessen, C., Favoreel, H., Ma, G., Osterrieder, N., de Schauwer, C., Piepers, S., van de Walle, G.R. Equid herpesvirus 1 (EHV1) infection of equine mesenchymal stem cells induces a pUL56-dependent downregulation of select cell surface markers. Vet. Microbiol. 2015, 176(1–2), 32–39.
[ 11 ] Khatri, M., Saif, Y.M. Influenza virus infects bone marrow mesenchymal stromal cells in vitro: Implications for bone marrow transplantation. Cell Transplant. 2013, 22(3), 461–468.
[ 12 ] Meisel, R., Heseler, K., Nau, J., Schmidt, S.K., Leineweber, M., Pudelko, S., Wenning, J., Zimmermann, A., Hengel, H., Sinzger, C., Degistirici, Z., Volker Sorg, R., Däubener, W. Cytomegalovirus infection impairs immunosuppressive and antimicrobial effector functions of human multipotent mesenchymal stromal cells. Mediators Inflamm. 2014, 2014, 1–7.
[ 13 ] Beys-da-Silva, W.O., Rosa, R.L., Santi, L., Berger, M., Park, S.K., Campos, A.R., Terraciano, P., Varela, A.P. M., Teixeira, T. F., Roehe, P. M., Quincozes-Santos, A., Yates, J.R., Souza, D. O., Cirne-Lima, E.O., Guimarães, J. A. Zika virus infection of human mesenchymal stem cells promotes differential expression of proteins linked to several neurological diseases. Mol. Neurobiol. 2018, 56(7), 4708–4717.
[ 14 ] Renaud, C., Xie, H., Seo, S., Kuypers, J., Cent, A., Corey, L., Leisenring, W., Boeckh, M., Englund, J. A. Mortality rates of human metapneumovirus and respiratory syncytial virus lower respiratory tract infections in hematopoietic cell transplantation recipients. Biol. Blood Marrow Transplant. 2013, 19(8), 1220–1226.
[ 15 ] Clementi, N., Ghosh, S., de Santis, M., Castelli, M., Criscuolo, E., Zanoni, I., Clementi, M., Mancini, N. Viral respiratory pathogens and lung injury. Clin. Microbiol. Rev. 2021, 34(3), e00103-20.
[ 16 ] Jethani, J., Samad, S., Kumar, P., Angel, B., Wig, N., Choudhary, A., Brijwal, M., Kumar, L., Dar, L. Human metapneumovirus infection in haematopoietic stem cell transplant recipients: a case series. VirusDisease 2021, 32(1), 140–145.
[ 17 ] Shah, D.P., Shah, P.K., Azzi, J.M., Chemaly, R.F. Parainfluenza virus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: A systematic review. Cancer Lett. 2016, 370(2), 358–364.
[ 18 ] Kim, Y.J., Guthrie, K.A., Waghmare, A., Walsh, E.E., Falsey, A.R., Kuypers, J., Cent, A., Englund, J.A., Boeckh, M. Respiratory syncytial virus in hematopoietic cell transplant recipients: Factors determining progression to lower respiratory tract disease. J. Infect. Dis. 2013, 209(8), 1195–1204.
[ 19 ] Shah, D. P., Shah, P. K., Azzi, J. M., el Chaer, F., Chemaly, R. F. Human metapneumovirus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: A systematic review. Cancer Lett. 2016, 379(1), 100–106.
[ 20 ] Naji, A., Eitoku, M., Favier, B., Deschaseaux, F., Rouas-Freiss, N., Suganuma, N. Biological functions of mesenchymal stem cells and clinical implications. Cell. Mol. Life Sci. 2019, 76(17), 3323–3348.
[ 21 ] Brügger, M., Démoulins, T., Barut, G.T., Zumkehr, B., Oliveira Esteves, B.I., Mehinagic, K., Haas, Q., Schögler, A., Rameix-Welti, M.A., Eléouët, J.F., Moehrlen, U., Marti, T.M., Schmid, R.A., Summerfield, A., Posthaus, H., Ruggli, N., Hall, S.R.R., Alves, M.P. Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection. PLoS Pathog. 2021, 17(7), e1009789.
[ 22 ] Wang, I.H., Burckhardt, C., Yakimovich, A., Greber, U. Imaging, tracking and computational analyses of virus entry and egress with the cytoskeleton. Viruses 2018, 10(4), 166.
[ 23 ] el Najjar, F., Cifuentes-Muñoz, N., Chen, J., Zhu, H., Buchholz, U.J., Moncman, C.L., Dutch, R.E. Human metapneumovirus induces reorganization of the actin cytoskeleton for direct cell-to-cell spread. PLoS Pathog. 2016, 12(9), e1005922.
[ 24 ] Singh, B.K., Pfaller, C.K., Cattaneo, R., Sinn, P.L. Measles virus ribonucleoprotein complexes rapidly spread across well-differentiated primary human airway epithelial cells along F-actin rings. mBio 2019, 10(6), e02434-19.
[ 25 ] Rodríguez-Fuentes, N., Rodríguez-Hernández, A.G., Enríquez-Jiménez, J., Alcántara-Quintana, L.E., Fuentes-Mera, L., Piña-Barba, M.C., Zepeda-Rodríguez, A., & Ambrosio, J.R. Nukbone® promotes proliferation and osteoblastic differentiation of mesenchymal stem cells from human amniotic membrane. Biochem, Biophys. Res. Commun. 2013, 434(3), 676–680.
[ 26 ] Rodríguez-Fuentes, N., Reynoso-Ducoing, O., Rodríguez-Hernández, A., Ambrosio-Hernández, J.R., Piña-Barba, M. C., Zepeda-Rodríguez, A., Cerbón-Cervantes, M.A., Tapia-Ramírez, J., Alcantara-Quintana, L.E. Isolation of human mesenchymal stem cells and their cultivation on the porous bone matrix. J. Vis. Exp. 2015, 96, e51999.
[ 27 ] Payment, P., Trudel M. Methods and Techniques in Virology; Marcel Dekker, INC. N.Y. USA, 1993, pp.309-310.
[ 28 ] Perezbusta-Lara, N., Tirado-Mendoza, R., Ambrosio-Hernández, J.R. Respiratory infections and coinfections: geographical and population patterns. Gaceta de México 2020, 156(4), 263–269.
[ 29 ] Persson, B.D., Jaffe, A.B., Fearns, R., Danahay, H. Respiratory syncytial virus can infect basal cells and alter human airway epithelial differentiation. PLoS One 2014, 9(7), e102368.
[ 30 ] Villenave, R., Shields, M.D., Power, U.F. Respiratory syncytial virus interaction with human airway epithelium. Trends Microbiol. 2013, 21(5), 238–244.
[ 31 ] Zhang, L., Collins, P.L., Lamb, R.A., Pickles, R.J. Comparison of differing cytopathic effects in human airway epithelium of parainfluenza virus 5 (W3A), parainfluenza virus type 3, and respiratory syncytial virus. Virology 2011, 421(1), 67–77.
[ 32 ] Villenave, R., Thavagnanam, S., Sarlang, S., Parker, J., Douglas, I., Skibinski, G., Heaney, L.G., McKaigue, J.P., Coyle, P.V., Shields, M.D., Power, U.F. In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo. PNAS 2012, 109(13), 5040–5045.
[ 33 ] Baron, S. Medical Microbiology 4th ed.; University of Texas Medical Branch at Galvestone: Galvestone, USA, 1996, Chapter 59 Paramixoviruses..
[ 34 ] Guo-Parke, H., Canning, P., Douglas, I., Villenave, R., Heaney, L.G., Coyle, P.V., Lyons, J.D., Shields, M.D., Power, U.F. Relative respiratory syncytial virus cytopathogenesis in upper and lower respiratory tract epithelium. Am. J. Respir. Crit. Care Med. 2013, 188(7), 842–851.