Chlamydia trachomatis Co-opts the FGF2 Signaling Pathway to Enhance Infection

Kim, Jung Hwa; Jiang, Shaobo; Elwell, Cherilyn A.; Engel, Joanne N.

doi:10.1371/journal.ppat.1002285

Cited by 58 publications

(62 citation statements)

References 74 publications

(84 reference statements)

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“…Chlamydia trachomatis, cytomegalovirus, herpes simplex virus, hepatitis C virus, and others activate GFR pathways, in many cases bridging via soluble factors (89)(90)(91)(92)(93). Further, cytomegalovirus, enterovirus 71, and human immunodeficiency virus type 1 also employ annexin A2 interactions during infection (50)(51)(52)(53)55).…”

Section: Discussionmentioning

confidence: 99%

Annexin A2 and S100A10 Regulate Human Papillomavirus Type 16 Entry and Intracellular Trafficking in Human Keratinocytes

Dziduszko

Ozbun

2013

J Virol

125

143

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Human papillomaviruses (HPVs) cause benign and malignant tumors of the mucosal and cutaneous epithelium. The initial events regulating HPV infection impact the establishment of viral persistence, which is requisite for malignant progression of HPV-infected lesions. However, the precise mechanisms involved in HPV entry into host cells, including the cellular factors regulating virus uptake, are not clearly defined. We show that HPV16 exposure to human keratinocytes initiates epidermal growth factor receptor (EGFR)-dependent Src protein kinase activation that results in phosphorylation and extracellular translocation of annexin A2 (AnxA2). HPV16 particles interact with AnxA2 in association with S100A10 as a heterotetramer at the cell surface in a Ca 2؉ -dependent manner, and the interaction appears to involve heparan-sulfonated proteoglycans. We show multiple lines of evidence that this interaction promotes virus uptake into host cells. An antibody to AnxA2 prevents HPV16 internalization, whereas an antibody to S100A10 blocks infection at a late endosomal/lysosomal site. These results suggest that AnxA2 and S100A10 have separate roles during HPV16 binding, entry, and trafficking. Our data additionally imply that AnxA2 and S100A10 may be involved in regulating the intracellular trafficking of virus particles prior to nuclear delivery of the viral genome.

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Section: Discussionmentioning

confidence: 99%

Annexin A2 and S100A10 Regulate Human Papillomavirus Type 16 Entry and Intracellular Trafficking in Human Keratinocytes

Dziduszko

Ozbun

2013

J Virol

125

143

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“…Our results suggest a more important role of glucuronosyltransferase I in Chlamydia attachment. Furthermore, FGF2 enhances binding of Chlamydia in an heparan sulfate proteoglycan-dependent manner (37). Candidate Chlamydia proteins involved in these interactions include the Chlamydia OmcB protein, which binds to glycosaminoglycans, such as heparan sulfate (38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Attachment ofChlamydia trachomatisL2 to host cells requires sulfation

Rosmarin

Carette

Olive

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Chlamydia trachomatis is a pathogen responsible for a prevalent sexually transmitted disease. It is also the most common cause of infectious blindness in the developing world. We performed a loss-of-function genetic screen in human haploid cells to identify host factors important in C. trachomatis L2 infection. We identified and confirmed B3GAT3 , B4GALT7 , and SLC35B2 , which encode glucuronosyltransferase I, galactosyltransferase I, and the 3′-phosphoadenosine 5′-phosphosulfate transporter 1, respectively, as important in facilitating Chlamydia infection. Knockout of any of these three genes inhibits Chlamydia attachment. In complementation studies, we found that the introduction of functional copies of these three genes into the null clones restored full susceptibility to Chlamydia infection. The degree of attachment of Chlamydia strongly correlates with the level of sulfation of the host cell, not simply with the amount of heparan sulfate. Thus, other, as-yet unidentified sulfated macromolecules must contribute to infection. These results demonstrate the utility of screens in haploid cells to study interactions of human cells with bacteria. Furthermore, the human null clones generated can be used to investigate the role of heparan sulfate and sulfation in other settings not limited to infectious disease.

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“…It is possible that these kinases might function redundantly in the internalization step. 29,37 The last stage in the cascade is probably regulated by another bacterial protein, CT166, which inactivates Rac1 (but not Rho A) via glucosylation, 38 thus completing the activation/ inactivation cycle of Rac1. In summation, this is a complex and tightly regulated process in which diverse bacterial and host proteins play essential roles in the attachment and entry of Chlamydia, in which Rac1 plays an important function throughout the process (Fig.…”

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confidence: 99%