Inhibition of cell growth by bafilomycin A1, a selective inhibitor of vacuolar H+-ATPase

Ohkuma, Shoji; Shimizu, Sakae; Noto, M; Sai, Yoshimichi; Kinoshita, Koichi; Tamura, Hiro Omi

doi:10.1007/bf02631364

Cited by 47 publications

(55 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experiments measuring the pH in cellular vesicles during treatment with acidification inhibitors have found that neither type of inhibitor raises the pH of endosomes to neutrality unless excessive concentrations are used, and the effectiveness of bafilomycin A1 and ammonium chloride in raising the pH was often not equivalent and can depend on cell type (37,42,67). We have shown that HMPV F protein-promoted fusion increases steadily as the pH to which the protein is exposed decreases (49).…”

Section: Discussionmentioning

confidence: 99%

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Schowalter

Chang

Robach

et al. 2009

J Virol

115

View full text Add to dashboard Cite

Human metapneumovirus (HMPV) is a significant respiratory pathogen classified in the Pneumovirinae subfamily of the paramyxovirus family. Recently, we demonstrated that HMPV F protein-promoted cell-cell fusion is stimulated by exposure to low pH, in contrast to what is observed for other paramyxovirus F proteins. In the present study, we examined the potential role of histidine protonation in HMPV F fusion and investigated the role of low pH in HMPV viral entry. Mutagenesis of the three ectodomain histidine residues of the HMPV F protein demonstrated that the mutation of a histidine in the heptad repeat B linker domain (H435) ablated fusion activity without altering cell surface expression or proteolytic processing significantly. Modeling of the HMPV F protein revealed several basic residues surrounding this histidine residue, and the mutation of these residues also reduced fusion activity. These results suggest that electrostatic repulsion in the heptad repeat B linker region may contribute to the triggering of HMPV F. In addition, we examined the effect of inhibitors of endosomal acidification or endocytosis on the entry of a recombinant green fluorescent proteinexpressing HMPV. Interestingly, chemicals that raise the pH of endocytic vesicles resulted in a 30 to 50% decrease in HMPV infection, while the inhibitors of endocytosis reduced infection by as much as 90%. These data suggest that HMPV utilizes an endocytic entry mechanism, in contrast to what has been hypothesized for most paramyxoviruses. In addition, our results indicate that HMPV uses the low pH of the endocytic pathway to enhance infectivity, though the role of low pH likely differs from classically described mechanisms.

show abstract

Section: Discussionmentioning

confidence: 99%

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Schowalter

Chang

Robach

et al. 2009

J Virol

115

View full text Add to dashboard Cite

show abstract

“…the erythroid cell differentia-K. Kinoshita et al IFEBS Letters 337 (1994) [221][222][223][224][225] tion of Friend leukemia cells; unpublished observation), due to its growth inhibitory activity [29], should help us to elucidate the general cascade of information transmission in cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Induction of phagocytic activity of M1 cells by an inhibitor of vacuolar FT‐ATPase, bafilomycin A₁

1994

Self Cite

View full text Add to dashboard Cite

Bafilomycin A,, a selective inhibitor of vacuolar H'-ATPase, time-and dose-dependently induced the differentiation of Ml cells, a murine myeloid leukemic cell line, into macrophage-like cells as revealed by the phagocytosis of polystyrene latex particles. This differentiation was inhibited not only by actinomycin D and cycloheximide but also by ST-638 (an inhibitor of tyrosine kinase). However, it was affected neither by K-252a (an inhibitor of C-kinase) nor by H-89 (an inhibitor of A-kinase), in contrast to the Ml cell differentiation induced by leukemia inhibitory factor &IF). Okadaic acid inhibited both the bafilomycin A,-induced and LIF-induced differentiation of Ml cells.

show abstract

“…These results are in close agreement with previous studies that have assessed the inhibition of VSV or MuLV-E by lysosomotropic agents (2,27,28,35). Experiments with BFLA1 were complicated by a toxic effect of the drug that inhibits cell growth (25,37). NIH 3T3 cell cultures treated with BFLA1 exhibited an initial lag in growth compared to untreated cells.…”

Section: Methodsmentioning

confidence: 99%

Infectious Entry by Amphotropic as well as Ecotropic Murine Leukemia Viruses Occurs through an Endocytic Pathway

Katen

Januszeski

Anderson

et al. 2001

J Virol

View full text Add to dashboard Cite

Infectious entry of enveloped viruses is thought to proceed by one of two mechanisms. pH-dependent viruses enter the cells by receptor-mediated endocytosis and are inhibited by transient treatment with agents that prevent acidification of vesicles in the endocytic pathway, while pH-independent viruses are not inhibited by such agents and are thought to enter the cell by direct fusion with the plasma membrane. Nearly all retroviruses, including amphotropic murine leukemia virus (MuLV) and human immunodeficiency virus type 1, are classified as pH independent. However, ecotropic MuLV is considered to be a pH-dependent virus. We have examined the infectious entry of ecotropic and amphotropic MuLVs and found that they were equally inhibited by NH 4 Cl and bafilomycin A. These agents inhibited both viruses only partially over the course of the experiments. Agents that block the acidification of endocytic vesicles also arrest vesicular trafficking. Thus, partial inhibition of the MuLVs could be the result of virus inactivation during arrest in this pathway. In support of this contention, we found that that the loss of infectivity of the MuLVs during treatment of target cells with the drugs closely corresponded to the loss of activity due to spontaneous inactivation at 37°C in the same period of time. Furthermore, the drugs had no effect on the efficiency of infection under conditions in which the duration of infection was held to a very short period to minimize the effects of spontaneous inactivation. These results indicate that the infectious processes of both ecotropic and amphotropic MuLVs were arrested rather than aborted by transient treatment of the cells with the drugs. We also found that infectious viruses were efficiently internalized during treatment. This indicated that the arrest occurred in an intracellular compartment and that the infectious process of both the amphotropic and ecotropic MuLVs very likely involved endocytosis. An important aspect of this study pertains to the interpretation of experiments in which agents that block endocytic acidification inhibit infectivity. As we have found with the MuLVs, inhibition of infectivity may be secondary to the block of endocytic acidification. While this strongly suggests the involvement of an endocytic pathway, it does not necessarily indicate a requirement for an acidic compartment during the infectious process. Likewise, a lack of inhibition during transient treatment with the drugs would not preclude an endocytic pathway for viruses that are stable during the course of the treatment.

show abstract

Inhibition of cell growth by bafilomycin A1, a selective inhibitor of vacuolar H+-ATPase

Cited by 47 publications

References 32 publications

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Induction of phagocytic activity of M1 cells by an inhibitor of vacuolar FT‐ATPase, bafilomycin A₁

Infectious Entry by Amphotropic as well as Ecotropic Murine Leukemia Viruses Occurs through an Endocytic Pathway

Contact Info

Product

Resources

About

Inhibition of cell growth by bafilomycin A1, a selective inhibitor of vacuolar H+-ATPase

Cited by 47 publications

References 32 publications

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry

Induction of phagocytic activity of M1 cells by an inhibitor of vacuolar FT‐ATPase, bafilomycin A1

Infectious Entry by Amphotropic as well as Ecotropic Murine Leukemia Viruses Occurs through an Endocytic Pathway

Contact Info

Product

Resources

About

Induction of phagocytic activity of M1 cells by an inhibitor of vacuolar FT‐ATPase, bafilomycin A₁