A prospective study comparing human metapneumovirus with other respiratory viruses in adults with hematologic malignancies and respiratory tract infections

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2581, USA.
The Journal of Infectious Diseases (Impact Factor: 5.78). 10/2005; 192(6):1061-5. DOI: 10.1086/432732
Source: PubMed

ABSTRACT Human metapneumovirus (hMPV) is a recently described paramyxovirus associated with upper and lower respiratory-tract infection (URI and LRI, respectively). We conducted a prospective study of URI and LRI in adults with hematologic malignancies during a 4-year period. We retrospectively tested samples by reverse-transcription polymerase chain reaction for hMPV and analyzed clinical data. Twenty-two (9%) of 251 episodes of respiratory infection tested positive for hMPV. Sixteen (73%) of the illnesses occurred in hematopoietic stem-cell transplant recipients. Nine patients with hMPV developed LRI; 3 of these patients died. hMPV is a common cause of respiratory infections in adults with hematologic malignancies, with associated morbidity and mortality.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Human metapneumovirus (HMPV) is a leading cause of respiratory disease in infants, children, and the elderly worldwide, yet no licensed vaccines exist. Live- attenuated vaccines present safety challenges, and protein subunit vaccines induce primarily antibody responses. Virus-like particles (VLPs) are an attractive alternative vaccine approach because of reduced safety concerns compared with live vaccines. We generated HMPV VLPs by expressing viral proteins in suspension- adapted human embryonic kidney epithelial (293-F) cells and found that the viral matrix (M) and fusion (F) proteins were sufficient to form VLPs. We previously reported that the VLPs resemble virus morphology and incorporate fusion-competent F protein (R. G. Cox, S. B. Livesay, M. Johnson, M. D. Ohi, and J.V. Williams, J.Virol. 86: 12148 - 12160, 2012), which we hypothesized would elicit F-specific antibody and T cell responses. In this study, we tested whether VLP immunization could induce protective immunity to HMPV by using a mouse model. C57BL/6 mice were injected twice intraperitoneally with VLPs alone or with adjuvant and subsequently challenged with HMPV. Mice were euthanized 5 days postinfection, and virus titers, levels of neutralizing antibodies, and numbers of CD3(+) T cells were quantified. Mice immunized with VLPs mounted an F-specific antibody response and generated CD8(+) T cells recognizing an F protein-derived epitope. VLP immunization induced a neutralizing-antibody response that was enhanced by the addition of either TiterMax Gold or alpha-galactosylceramide adjuvant, though adjuvant reduced cellular immune responses. Two doses of VLPs conferred complete protection from HMPV replication in the lungs of mice and were not associated with a Th2-skewed cytokine response. These results suggest that nonreplicating VLPs are a promising vaccine candidate for HMPV.
    Journal of Virology 03/2014; 88(11). DOI:10.1128/JVI.00332-14 · 4.65 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human metapneumovirus (hMPV), discovered in 2001, most commonly causes upper and lower respiratory tract infections in young children, but is also a concern for elderly subjects and immune-compromised patients. hMPV is the major etiological agent responsible for about 5% to 10% of hospitalizations of children suffering from acute respiratory tract infections. hMPV infection can cause severe bronchiolitis and pneumonia in children, and its symptoms are indistinguishable from those caused by human respiratory syncytial virus. Initial infection with hMPV usually occurs during early childhood, but re-infections are common throughout life. Due to the slow growth of the virus in cell culture, molecular methods (such as reverse transcriptase PCR (RT-PCR)) are the preferred diagnostic modality for detecting hMPV. A few vaccine candidates have been shown to be effective in preventing clinical disease, but none are yet commercially available. Our understanding of hMPV has undergone major changes in recent years and in this article we will review the currently available information on the molecular biology and epidemiology of hMPV. We will also review the current therapeutic interventions and strategies being used to control hMPV infection, with an emphasis on possible approaches that could be used to develop an effective vaccine against hMPV.
    International Journal of Infectious Diseases 08/2014; 25. DOI:10.1016/j.ijid.2014.03.1394 · 2.33 Impact Factor

Full-text (2 Sources)

Available from
Jun 1, 2014