Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats <i>Sigmodon hispidus</i>
Human metapneumovirus (hMPV) is an important cause of respiratory disease in immunocompromised individuals, yet hMPV infection has not been modeled before in immunocompromised animals. In this work, cotton rats <i>S. hispidus</i> immunosuppressed by cyclophosphamide were infected with hM...
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MDPI AG
2023-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/2/476 |
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| author | Kevin C. Yim Jarrod J. Mousa Jorge C. G. Blanco Sonnie Kim Marina S. Boukhvalova |
| author_facet | Kevin C. Yim Jarrod J. Mousa Jorge C. G. Blanco Sonnie Kim Marina S. Boukhvalova |
| author_sort | Kevin C. Yim |
| collection | DOAJ |
| description | Human metapneumovirus (hMPV) is an important cause of respiratory disease in immunocompromised individuals, yet hMPV infection has not been modeled before in immunocompromised animals. In this work, cotton rats <i>S. hispidus</i> immunosuppressed by cyclophosphamide were infected with hMPV, and viral replication and pulmonary inflammation in these animals were compared to those in normal hMPV-infected <i>S. hispidus</i>. The efficacy of prophylactic and therapeutic administration of the anti-hMPV antibody MPV467 was also evaluated. Immunosuppressed animals had higher pulmonary and nasal titers of hMPV on day 5 post-infection compared to normal animals, and large amounts of hMPV were still present in the respiratory tract of immunosuppressed animals on days 7 and 9 post-infection, indicating prolonged viral replication. Immunosuppression was accompanied by reduced pulmonary histopathology in hMPV-infected cotton rats compared to normal animals; however, a delayed increase in pathology and pulmonary chemokine expression was seen in immunosuppressed cotton rats. Prophylactic and therapeutic MPV467 treatments protected both upper and lower respiratory tracts against hMPV infection. The lung pathology and pulmonary expression of IP-10 and MIP-1α mRNA were reduced by therapeutic MPV467 administration. These results indicate that immunosuppressed cotton rats represent a useful model for studying hMPV pathogenesis and for evaluating therapeutics that could alleviate hMPV-induced disease in immunocompromised subjects. |
| first_indexed | 2024-03-11T08:00:46Z |
| format | Article |
| id | doaj.art-72300d55b1a9440fad55fae81e7ca724 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T08:00:46Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-72300d55b1a9440fad55fae81e7ca7242023-11-16T23:49:32ZengMDPI AGViruses1999-49152023-02-0115247610.3390/v15020476Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats <i>Sigmodon hispidus</i>Kevin C. Yim0Jarrod J. Mousa1Jorge C. G. Blanco2Sonnie Kim3Marina S. Boukhvalova4Sigmovir Biosystems, Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USACenter for Vaccines and Immunology, Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USASigmovir Biosystems, Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USANIH/NIAID, Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases, Rockville, MD 20852, USASigmovir Biosystems, Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USAHuman metapneumovirus (hMPV) is an important cause of respiratory disease in immunocompromised individuals, yet hMPV infection has not been modeled before in immunocompromised animals. In this work, cotton rats <i>S. hispidus</i> immunosuppressed by cyclophosphamide were infected with hMPV, and viral replication and pulmonary inflammation in these animals were compared to those in normal hMPV-infected <i>S. hispidus</i>. The efficacy of prophylactic and therapeutic administration of the anti-hMPV antibody MPV467 was also evaluated. Immunosuppressed animals had higher pulmonary and nasal titers of hMPV on day 5 post-infection compared to normal animals, and large amounts of hMPV were still present in the respiratory tract of immunosuppressed animals on days 7 and 9 post-infection, indicating prolonged viral replication. Immunosuppression was accompanied by reduced pulmonary histopathology in hMPV-infected cotton rats compared to normal animals; however, a delayed increase in pathology and pulmonary chemokine expression was seen in immunosuppressed cotton rats. Prophylactic and therapeutic MPV467 treatments protected both upper and lower respiratory tracts against hMPV infection. The lung pathology and pulmonary expression of IP-10 and MIP-1α mRNA were reduced by therapeutic MPV467 administration. These results indicate that immunosuppressed cotton rats represent a useful model for studying hMPV pathogenesis and for evaluating therapeutics that could alleviate hMPV-induced disease in immunocompromised subjects.https://www.mdpi.com/1999-4915/15/2/476hMPVcotton ratimmunocompromisedMPV467 |
| spellingShingle | Kevin C. Yim Jarrod J. Mousa Jorge C. G. Blanco Sonnie Kim Marina S. Boukhvalova Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats <i>Sigmodon hispidus</i> Viruses hMPV cotton rat immunocompromised MPV467 |
| title | Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats <i>Sigmodon hispidus</i> |
| title_full | Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats <i>Sigmodon hispidus</i> |
| title_fullStr | Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats <i>Sigmodon hispidus</i> |
| title_full_unstemmed | Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats <i>Sigmodon hispidus</i> |
| title_short | Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats <i>Sigmodon hispidus</i> |
| title_sort | human metapneumovirus hmpv infection and mpv467 treatment in immunocompromised cotton rats i sigmodon hispidus i |
| topic | hMPV cotton rat immunocompromised MPV467 |
| url | https://www.mdpi.com/1999-4915/15/2/476 |
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