Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats Sigmodon hispidus.
Viruses
; 15(2)2023 02 09.
Article
en En
| MEDLINE
| ID: mdl-36851691
ABSTRACT
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 S. hispidus immunosuppressed by cyclophosphamide were infected with hMPV, and viral replication and pulmonary inflammation in these animals were compared to those in normal hMPV-infected S. hispidus. 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sigmodontinae
/
Huésped Inmunocomprometido
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Infecciones por Paramyxoviridae
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Metapneumovirus
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Viruses
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos