Human Metapneumovirus Induces Mucin 19 Which Contributes to Viral Pathogenesis

Abstract

Human Metapneumovirus (HMPV) remains one of the most common viral infections causing acute respiratory tract infections, especially in young children, elderly, and immunocompromised populations. Clinical symptoms can range from mild respiratory symptoms to severe bronchiolitis and pneumonia. The production of mucus is a common feature during HMPV infection, but its contribution to HMPV-induced pathogenesis and immune response is largely unknown. Mucins are a major component of mucus and they could have an impact on how the host responds to infections. Using an in vitro system and a mouse model of infection, we identified that Mucin 19 is predominantly expressed in the respiratory tract upon HMPV infection. Moreover, the lack of Muc19 led to an improved disease, lower lung viral titers and a decrease in the number of CD4+ T cells. These data indicate that mucin 19 contributes to the activation of the immune response to HMPV and to HMPV-induced pathogenesis.

METTL3aggravates cell damage induced byStreptococcus pneumoniaevia theNEAT1/CTCF/MUC19axis

“…Previously, it has been observed that MUC19 downregulation alleviates lung viral infection diseases. 18 Here, it was indicated that MUC19 transcription levels increased after SP induction and decreased after METTL3 silencing but increased again after NEAT1 overexpression ( p < 0.05, Figure 5C). Based on this, it was hypothesized that the binding of NEAT1 to CTCF promotes the transcription of MUC19.…”

“…It has been suggested that in human alveolar basal epithelial cells, HMPV can induce MUC19 production, 29 which is also involved in viral replication in the lungs of HMPV-infected mice. 18 Here, it was revealed that the SP induction elevated the MUC19 transcription levels, and MUC19 overexpression through intracellular transfection increased apoptosis and inflammatory factors in SP-induced AECs. Another study reported that overexpression of MUC19 can reduce oxidative stress and inflammation levels in AECs by inhibiting the TLR4/NF-κB signaling pathway.…”

“…In the lungs, there are four secreted MUCs: MUC2, MUC5AC, MUC5B, and MUC19 17 . It has been indicated that in the lungs of human metapneumovirus (HMPV)‐infected mice, MUC19 is significantly increased and its knockdown reduces HMPV‐induced lung inflammation 18 . Currently, the research on the specific MUC19 pathways in pneumonia is limited.…”

“…17 It has been indicated that in the lungs of human metapneumovirus (HMPV)-infected mice, MUC19 is significantly increased and its knockdown reduces HMPV-induced lung inflammation. 18 Currently, the research on the specific MUC19 pathways in pneumonia is limited. This investigation elucidated the effect of METTL3 on SP-induced AECs and explored the downstream pathways of METTL3 to provide a new theoretical basis for the treatment of bacterial pneumonia.…”

Abnormal Airway Mucus Secretion Induced by Virus Infection

“…HMPV infection significantly increased expression of MUC1, MUC2, MUC4, MUC5AC, and MUC19 in both normal human bronchial epithelial cells and BALB/c mice ( 82 ). A recent study compared the differences in mucin expression between hMPV and RSV infections.…”