Human Metapneumovirus Persists in BALB/c Mice despite the Presence of Neutralizing Antibodies

• Rene Alvarez

  Division of Respiratory and Enteric Viruses

• Kevin S. Harrod

  Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico

• Wun-Ju Shieh

  Infectious Disease Pathology Activity, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

• Sherif Zaki

  Infectious Disease Pathology Activity, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

• Ralph A. Tripp

  Division of Respiratory and Enteric Viruses

抄録

Human metapneumovirus (HMPV) has emerged as an important human respiratory pathogen causing upper and lower respiratory tract infections in young children and older adults. Recent epidemiological evidence indicates that HMPV may cocirculate with respiratory syncytial virus, and HMPV infection has been associated with other respiratory diseases. In this study, we show that BALB/c mice are susceptible to HMPV infection, the virus replicates in the lungs with biphasic growth kinetics in which peak titers occur at days 7 and 14 postinfection (p.i.), and infectious HMPV can be recovered from lungs up to day 60 p.i. In addition, we show that genomic HMPV RNA can be detected in the lungs for ≥180 days p.i. by reverse transcription-PCR; however, neither HMPV RNA nor infectious virus can be detected in serum, spleen, kidneys, heart, trachea, and brain tissue. Lung histopathology revealed prevalent mononuclear cell infiltration in the interstitium beginning at day 2 p.i. and peaking at day 4 p.i. which decreased by day 14 p.i. and was associated with airway remodeling. Increased mucus production evident at day 2 p.i. was concordant with increased bronchial and bronchiolar inflammation. HMPV-specific antibodies were detected by day 14 p.i., neutralizing antibody titers reached ≥6.46 log 2 end-point titers by day 28 p.i., and depletion of T cells or NK cells resulted in increased HMPV titers in the lungs, suggesting some immune control of viral persistence. This study shows that BALB/c mice are amenable for HMPV studies and indicates that HMPV persists as infectious virus in the lungs of normal mice for several weeks postinfection.

収録刊行物

• Journal of Virology

  Journal of Virology 78 (24), 14003-14011, 2004-12-15

  American Society for Microbiology

キーワード

• Virology
• Insect Science
• Immunology
• Microbiology

詳細情報

• CRID: 1363670321304801152
• NII論文ID: 30020801637
• DOI: 10.1128/jvi.78.24.14003-14011.2004
• ISSN: 10985514
• ISSN: 0022538X
• Web Site: https://journals.asm.org/doi/pdf/10.1128/JVI.78.24.14003-14011.2004
• データソース種別:
  • Crossref
  • CiNii Articles