Human metapneumovirus uses endocytosis pathway for host cell entry

Yang, Hui; He, Hao; Tan, Bin; Liu, Enmei; Zhao, Xiaodong; Zhao, Yongkun

doi:10.1016/j.mcp.2016.06.003

Cited by 10 publications

(6 citation statements)

References 27 publications

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“…The binding of hMPV and RGD‐binding integrin activates downstream signaling cascades and promotes clathrin‐mediated endocytosis . Our previous study had showed that hMPV existed whole particles in the cytoplasm and membrane fusion occurred in the cytoplasm . Taken together, these data indicated that hMPV may enter host cells via endocytosis.…”

Section: Discussionmentioning

confidence: 77%

“…According to different vectors, the main four kinds of endocytic pathways are defined, such as clathrin‐, caveolae‐, cholesterol‐mediated endocytosis, and macropinocytosis . Recently, hMPV had been found to invade BEAS‐2B cells via endocytosis and in our previous studies, we also found that hMPV uses endocytosis pathway in Vero E6 and LLC‐MK2 cell lines …”

Section: Introductionmentioning

confidence: 84%

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The role of lipid rafts in cell entry of human metapneumovirus

Chen

Yang

et al. 2019

Journal of Medical Virology

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Human metapneumovirus (hMPV) is a crucial pathogen in children. A cell entry is the first step for infection. Our previous study indicated that there was an endocytosis pathway for hMPV cell entry. Lipid raft is a specific structure at the cell surface and it has been demonstrated to play an important role in endocytosis process of many viruses. In this study, we investigated whether and how lipid raft can take part in the hMPV entry. The confocal microscope was used to detect colocalization of hMPV and lipid raft marker. We demonstrated that colocalizations were increased along with the viral infection and hMPV particles transferred to the perinuclear region with lipid raft. When specific lipid raft inhibitors: methyl‐β cyclodextrin and nystatin were used, hMPV cell entry was inhibited and viral titer decreased dramatically. With the replenishment of exogenous cholesterol, hMPV recovered quickly. These data suggest that lipid raft plays an important role in hMPV endocytosis and maybe one of the pathways for hMPV cell entry.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 84%

The role of lipid rafts in cell entry of human metapneumovirus

Chen

Yang

et al. 2019

Journal of Medical Virology

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“…The isolation of A 2 hMPV viral strain, showed the first signs of CPE in the third blind passage, at 14 d.p.i, characterized by cell rounding and formation of refractive corsages of cells, similarly to what has been previously reported (Abiko et al, 2007; Boivin et al, 2002; Chan et al, 2003; Deffrasnes et al, 2005; Kinder et al, 2020). In contrast, other authors have described that hMPV can appear as a syncytium (Bernal et al, 2019; Sato et al, 2017; Van Den Hoogen et al, 2001; Yang et al, 2016) such as RSV (member of the same family) and this difference in CPE may be related to the cell lines that were infected (e.g. LLC-MK2) or to the viral genotype (Jumat et al, 2014; Nao et al, 2019; Reina et al, 2007; Tollefson et al, 2010; Williams et al, 2005; Zhang et al, 2012b).…”

Section: Discussionmentioning

confidence: 94%

“…In this sense, it is known that isolation of respiratory viruses from clinical specimens often show low efficiency in in vitro cell cultures. This low efficiency could be associated to the cell type and/or the virus subtype and its entry pathway (Cifuentes-muñoz et al, 2017; Cifuentes-Muñoz and Ellis Dutch, 2019; Cox et al, 2015; Kinder et al, 2020; Lee et al, 2019; Yang et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Actin cytoskeleton dynamics affect replication of Human Metapneumovirus

Rodriguez

Gil

Cámara

et al. 2022

Preprint

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Human metapneumovirus (hMPV) is a virus responsible for acute respiratory infection in humans with clinical and epidemiological relevance in pediatric, immunocompromised, and elderly populations. Little is known about hMPV in vitro replication biological processes and their relationship with cellular structures such as the cytoskeleton. Our goal was to evaluate the viral replication curve in order to study the role of the actin cytoskeleton in hMPV replication at different stages of viral growth. Human metapneumovirus was isolated in a Vero cell line from a clinical sample and identified as A2 genotype. The cytopathic effect was detected by the appearance of cell rounding and refractory cell clusters. The growth curve showed that viral replication maximum level was between 48 and 72 h.p.i. The highest percentage of infected cells and intracellular hMPV-protein were detected at the early stages of the replication cycle (8 h.p.i). Disruption of actin microfilaments with cytochalasin D (CytD) during the early events of infection provoked an increase in both intracellular and extracellular viruses. We demonstrate that the early phase of the hMPV curve is crucial for viral replication. We also show that disruption of actin filaments during this time increments both viral protein expression in the cytoplasm and the release of viruses to the extracellular space. This study contributes to elucidate wild-type hMPV growth kinetics, providing new insights on the actin cytoskeleton role in viral replication mechanisms. In addition, it points out putative targets to develop new antiviral treatments.

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“…Follow up studies utilizing single virus particle tracking and fusion assays showed that a portion of hMPV fuses at the plasma membrane as is typical of paramyxoviruses, but also that a significant fraction of the virus is endocytosed and fuses with endosomal membranes in a manner characteristic of low pH-dependent viruses, such as influenza A virus (IAV) [13][14][15]. These data suggested that hMPV utilizes a bifurcated cellular entry strategy with characteristics typified by both SeV and IAV.…”

Section: Introductionmentioning

confidence: 95%

Opposing roles of endosomal innate immunity proteins IFITM3 and TLR7 in human metapneumovirus infection

McMichael

Kenney

Zhang

et al. 2018

Preprint

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Human metapneumovirus (hMPV) utilizes a bifurcated cellular entry strategy, fusing either with the plasma membrane or, after endocytosis, with the endosome membrane. Whether cellular factors restrict or enhance either entry pathway is largely unknown. We found that the interferon-induced transmembrane protein 3 (IFITM3) inhibits hMPV infection to an extent similar to endocytosis-inhibiting drugs, and an IFITM3 variant that accumulates at the plasma membrane in addition to its endosome localization provided increased virus restriction. Mechanistically, IFITM3 blocks hMPV F protein-mediated membrane fusion, and inhibition of infection was reversed by the membrane destabilizing drug amphotericin B. Conversely, we unexpectedly found that infection by some hMPV strains is enhanced by Toll-like receptor 7 (TLR7), an endosomal protein, suggesting that cellular entry via endocytosis may be particularly advantageous for hMPV despite eventual restriction of this pathway upon induction of IFITM3. Overall, our results identify IFITM3 and TLR7 as endosomal factors differentially regulating hMPV infection.

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Human metapneumovirus uses endocytosis pathway for host cell entry

Cited by 10 publications

References 27 publications

The role of lipid rafts in cell entry of human metapneumovirus

The role of lipid rafts in cell entry of human metapneumovirus

Actin cytoskeleton dynamics affect replication of Human Metapneumovirus

Opposing roles of endosomal innate immunity proteins IFITM3 and TLR7 in human metapneumovirus infection

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