Human Metapneumovirus: Mechanisms and Molecular Targets Used by the Virus to Avoid the Immune System.

Jorge A Soto,Margarita K Lay,Magdalena S Pizarro-Ortega,Felipe M Benavente,Pablo A Gonzalez,Claudia Riedel,Nicolás M S Gálvez,Susan M Bueno,Alexis M Kalergis

doi:10.3389/fimmu.2018.02466

Abstract

Human metapneumovirus (hMPV) is a respiratory virus, first reported the year 2001. Since then, it has been described as one of the main etiological agents that causes acute lower respiratory tract infections (ALRTIs), which is characterized by symptoms such as bronchiolitis, wheezing and coughing. Susceptible population to hMPV-infection includes newborn, children, elderly and immunocompromised individuals. This viral agent is a negative-sense, single-stranded RNA enveloped virus, that belongs to the Pneumoviridae family and Metapneumovirus genus. Early reports—previous to 2001—state several cases of respiratory illness without clear identification of the responsible pathogen, which could be related to hMPV. Despite the similarities of hMPV with several other viruses, such as the human respiratory syncytial virus or influenza virus, mechanisms used by hMPV to avoid the host immune system are still unclear. In fact, evidence indicates that hMPV induces a poor innate immune response, thereby affecting the adaptive immunity. Among these mechanisms, is the promotion of an anergic state in T cells, instead of an effective polarization or activation, which could be induced by low levels of cytokine secretion. Further, the evidences support the notion that hMPV interferes with several pattern recognition receptors (PRRs) and cell signaling pathways triggered by interferon-associated genes. However, these mechanisms reported in hMPV are not like the ones reported for hRSV, as the latter has two non-structural proteins that are able to inhibit these pathways. Several reports suggest that viral glycoproteins, such as G and SH, could play immune-modulator roles during infection. In this work, we discuss the state of the art regarding the mechanisms that underlie the poor immunity elicited by hMPV. Importantly, these mechanisms will be compared with those elicited by other common respiratory viruses.

Highlights

Human Metapneumovirus is a respiratory virus discovered by van Den Hoogen et al the year 2001, in samples from Dutch children with acute lower respiratory tract illness (ALRTI) [1]
This study suggests that, despite the fact that infection caused by Human metapneumovirus (hMPV) shares similarities with those caused by human respiratory syncytial virus (hRSV)—including symptoms and pathology—hMPV induces significantly lower levels of respiratory inflammatory cytokines, as compared with the response observed in hRSV-infected children [55]
Some TLRs involved with hMPV-infection have been studied (Figure 2), suggesting that the absence of toll-like receptor 4 (TLR4) in mice infected with hMPV results in a decrease in the production of cytokines, FIGURE 2 | Toll-like receptors (TLRs) and their role in the evasion of the immune response induced by hMPV

Summary

Introduction

Human Metapneumovirus (hMPV) is a respiratory virus discovered by van Den Hoogen et al the year 2001, in samples from Dutch children with acute lower respiratory tract illness (ALRTI) [1]. Another study showed that the SH hMPV mutant strain did not affect viral replication capacity when compared to the WT virus, but it did exhibit an inhibition of the NF-kB pathway in human lung epithelial cells [29].

Results

Conclusion