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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Virology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1402589

Transcriptome profiling of macrophages persistently infected with human respiratory syncytial virus and effect of recombinant Taenia solium calreticulin on immune-related genes

Provisionally accepted
Evelyn Rivera-Toledo Evelyn Rivera-Toledo 1Miguel A. Fernández-Rojas Miguel A. Fernández-Rojas 1CARLOS SANTIAGO CARLOS SANTIAGO 1Mayra C. Rivera Mayra C. Rivera 1Vania Hernández-Bautista Vania Hernández-Bautista 1Fernanda Ávila-Horta Fernanda Ávila-Horta 1Ana Flisser Ana Flisser 1Fela Mendlovic Fela Mendlovic 1,2*
  • 1 National Autonomous University of Mexico, México City, México, Mexico
  • 2 Anahuac University of North Mexico, Huixquilucan de Degollado, México, Mexico

The final, formatted version of the article will be published soon.

    Human respiratory syncytial virus (hRSV) is a main cause of bronchiolitis in infants and its persistence has been described in immunocompromised subjects. Using a comprehensive microarray approach, we analyzed the transcriptome profile of a macrophage cell line that has supported hRSV persistence for over 150 passages. We compared the gene expression of persistently infected and non-infected macrophages. We also evaluated the effect of a recombinant Taenia solium-derived calreticulin (rTsCRT) on hRSV-infected macrophage gene transcription, as well as on cytokine production and number of copies of the persistent hRSV genome. Our results showed that hRSV long-term virus infection significantly alters mRNA expression of antiviral, inflammatory, as well as arginine and lipid metabolismassociated genes, revealing a transcriptional signature that suggests a mixed M1/M2 phenotype. The resulting host-virus equilibrium allows for the regulation of viral replication while evading the antiviral and proinflammatory responses. Interestingly, rTsCRT stimulus upregulated Tnfα, Il6 and Nos2 mRNA. We found increased levels of both proinflammatory cytokines and nitrite levels in the conditioned media of persistent macrophages treated with rTsCRT. This increase was associated with a significant reduction in viral genome copies. We conclude that hRSV persistently infected macrophages retain responsiveness to external stimuli and demonstrate that the profound changes induced by viral persistence are potentially reversible. Our observations contribute to the understanding of the mechanisms related to hRSV persistence in macrophages and have implications for the development of targeted therapies to eliminate persistent infections or reduce the negative effects related with chronic inflammatory diseases associated with hRSV infection.

    Keywords: P388D1 cell line, viral persistence, Antiviral activity, Calreticulin, HRSV

    Received: 17 Mar 2024; Accepted: 05 Aug 2024.

    Copyright: © 2024 Rivera-Toledo, Fernández-Rojas, SANTIAGO, Rivera, Hernández-Bautista, Ávila-Horta, Flisser and Mendlovic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Fela Mendlovic, National Autonomous University of Mexico, México City, 04510, México, Mexico

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