Human metapneumovirus: review of an important respiratory pathogen

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.

Keywords: Bronchiolitis; Human metapneumovirus; Respiratory diseases; Viral pneumonia.

Figure 1

Schematic diagram of the human metapneumovirus particle and the ribonucleoprotein (RNP) complex.

Figure 2

Genomic organization of (a) human metapneumovirus (hMPV) and (b) respiratory syncytial virus (RSV), showing the important differences between the two viruses. In comparison to hMPV, RSV expresses two extra proteins, NS1 and NS2, differs in the organization of SH and G proteins, and the reading frames for M2 and L overlap each other. N, nucleoprotein; P, phosphoprotein; M, matrix protein; F, fusion protein; SH, small hydrophobic protein; G, attachment protein; L, large polymerase protein; NS1 and NS2, non-structural proteins 1 and 2.

Figure 3

Geographical distribution of hMPV genotypes. Map showing the geographical distribution of hMPV genotypes among humans. Human metapneumovirus isolates are divided into four major subgroups (A1, A2, B1, and B2) and each has its own geographical localization.

Figure 4

Molecular events in the pathogenesis of hMPV infection. Virus attachment to toll-like receptors (TLR) of macrophage and/or dendritic cells activates several adapter molecules of the immune system (TRIF and MYD88), which in turn activates Nuclear factor kappa beta (NFκβ). RNA of internalized virus is detected by cytoplasmic RIG1-like receptor (RLR), which in turn activates NFκβ by activation of mitochondrial antiviral signalling protein (MAVS) and transcription activators interferon regulatory factors 3 and 7 (IRF-3 and IRF-7). Finally NFκβ and IRFs induce the production of several interferons and interleukins.