Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have characterized the entry leading to productive infection of a type C FMDV in two cell lines widely used for virus growth, BHK-21 and IBRS-2. Inhibition of clathrin-mediated endocytosis by sucrose treatment decreased both cell entry and virus multiplication. Evidence of a direct requirement of clathrin for productive viral entry was obtained using BHK21-tTA/anti-CHC cells, which showed a significant reduction of viral entry and infection when the synthesis and functionality of clathrin heavy chain was inhibited (Tet- cells). This was also observed for vesicular stomatitis virus (VSV) productive entry. The effect of NH(4)Cl and concanamycin A on FMDV entry and infection was consistent with the requirement of acidic compartments for decapsidation and virus replication. As expected from its higher stability at acidic pH, this requirement was higher for VSV. Since BHK-21 and IBRS-2 cells expressed caveolin-1, we explored the effect on productive virus entry of drugs that interfere with caveolae-mediated endocytosis. Treatment with nystatin did not reduce entry and infection of FMDV or VSV, while cholesterol depletion with MbetaCD significantly inhibited both steps of the FMDV cycle, indicating that plasma membrane cholesterol is required for virus productive entry.
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PMID:Productive entry of type C foot-and-mouth disease virus into susceptible cultured cells requires clathrin and is dependent on the presence of plasma membrane cholesterol. 1771 53

It has recently been shown that cell entry of mouse hepatitis virus type 2 (MHV-2) is mediated through endocytosis (Z. Qiu et al., J. Virol. 80:5768-5776, 2006). However, the molecular mechanism underlying MHV-2 entry is not known. Here we employed multiple chemical and molecular approaches to determine the molecular pathways for MHV-2 entry. Our results showed that MHV-2 gene expression and infectivity were significantly inhibited when cells were treated with chemical and physiologic blockers of the clathrin-mediated pathway, such as chlorpromazine and hypertonic sucrose medium. Furthermore, viral gene expression was significantly inhibited when cells were transfected with a small interfering RNA specific to the clathrin heavy chain. However, these treatments did not affect the infectivity and gene expression of MHV-A59, demonstrating the specificity of the inhibitions. In addition, overexpression of a dominant-negative mutant of caveolin 1 did not have any effect on MHV-2 infection, while it significantly blocked the caveolin-dependent uptake of cholera toxin subunit B. These results demonstrate that MHV-2 utilizes the clathrin- but not caveolin-mediated endocytic pathway for entry. Interestingly, when the cells transiently overexpressed a dominant-negative form (DIII) of Eps15, which is thought to be an essential component of the clathrin pathway, viral gene expression and infectivity were unaffected, although DIII expression blocked transferrin uptake and vesicular stomatitis virus infection, which are dependent on clathrin-mediated endocytosis. Thus, MHV-2 entry is mediated through clathrin-dependent but Eps15-independent endocytosis.
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PMID:Mouse hepatitis virus type 2 enters cells through a clathrin-mediated endocytic pathway independent of Eps15. 1855 Jun 63

Ebola virus (EBOV) infects several cell types and while viral entry is known to be pH-dependent, the exact entry pathway(s) remains unknown. To gain insights into EBOV entry, the role of several inhibitors of clathrin-mediated endocytosis in blocking infection mediated by HIV pseudotyped with the EBOV envelope glycoprotein (EbGP) was examined. Wild type HIV and envelope-minus HIV pseudotyped with Vesicular Stomatitis Virus glycoprotein (VSVg) were used as controls to assess cell viability after inhibiting clathrin pathway. Inhibition of clathrin pathway using dominant-negative Eps15, siRNA-mediated knockdown of clathrin heavy chain, chlorpromazine and sucrose blocked EbGP pseudotyped HIV infection. Also, both chlorpromazine and Bafilomycin A1 inhibited entry of infectious EBOV. Sensitivity of EbGP pseudotyped HIV as well as infectious EBOV to inhibitors of clathrin suggests that EBOV uses clathrin-mediated endocytosis as an entry pathway. Furthermore, since chlorpromazine inhibits EBOV infection, novel therapeutic modalities could be designed based on this lead compound.
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PMID:Ebola virus uses clathrin-mediated endocytosis as an entry pathway. 2020 62

Kif5b-driven anterograde transport and clathrin-mediated endocytosis (CME) are responsible for opposite intracellular trafficking, contributing to plasma membrane homeostasis. However, whether and how the two trafficking processes coordinate remain unclear. Here, we show that Kif5b directly interacts with clathrin heavy chain (CHC) at a region close to that for uncoating catalyst (Hsc70) and preferentially localizes on relatively large clathrin-coated vesicles (CCVs). Uncoating in vitro is decreased for CCVs from the cortex of kif5b conditional knockout (mutant) mouse and facilitated by adding Kif5b fragments containing CHC-binding site, while cell peripheral distribution of CHC or Hsc70 keeps unaffected by Kif5b depletion. Furthermore, cellular entry of vesicular stomatitis virus that internalizes into large CCV is inhibited by Kif5b depletion or introducing a dominant-negative Kif5b fragment. These findings showed a new role of Kif5b in regulating large CCV-mediated CME via affecting CCV uncoating, indicating Kif5b as a molecular knot connecting anterograde transport to CME.
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PMID:A new role of anterograde motor Kif5b in facilitating large clathrin-coated vesicle mediated endocytosis via regulating clathrin uncoating. 3060 1

Clathrin-mediated endocytosis is a mechanism used for the invasion of cells by a variety of viruses. Mortalin protein is involved in a variety of cellular functions and plays a role in viral infection. In this study, we found that mortalin significantly inhibited the replication of porcine epidemic diarrhea virus (PEDV) through restricting virus entry. Mechanistically, a biochemical interaction between the carboxyl terminus of mortalin and clathrin heavy chain (CLTC) was been found, and mortalin could induce CLTC degradation through the proteasomal pathway, thereby inhibiting the clathrin-mediated endocytosis of PEDV into host cells. In addition, artificial changes in mortalin expression affected the cell entry of transferrin, further confirming the above results. Finally, we confirmed that this host-mounted antiviral mechanism was broadly applicable to other viruses, such as vesicular stomatitis virus (VSV), rotavirus (RV), and transmissible gastroenteritis virus (TGEV), which use the same clathrin-mediated endocytic to entry. These results reveal a new function of mortalin in inhibiting endocytosis, and provide a novel strategy for treating PEDV infections.
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PMID:Mortalin restricts porcine epidemic diarrhea virus entry by downregulating clathrin-mediated endocytosis. 3176 73