HPV entry into cells

Aksoy, Pınar; Gottschalk, Elinor; Meneses, Patricio

doi:10.1016/j.mrrev.2016.09.004

Cited by 73 publications

(94 citation statements)

References 103 publications

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“…HPV infection occurs following microabrasions exposing the basement membrane and polarized adherent basal keratinocytes to HPV 34,35 . Following interactions of the viral capsid proteins with ECM, apical cellular proteins, and receptors, the HPV capsid is internalized and undergoes retrograde endosomal trafficking toward the nucleus, where it resides within vesicles until breakdown of the nuclear envelope 36 .…”

Section: Discussionmentioning

confidence: 99%

Optimization of human papillomavirus-based pseudovirus techniques for efficient gene transfer

Gilson

Gibson

Androphy

2020

Preprint

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Human papillomavirus (HPV) L1 and L2 capsid proteins self-assemble into virions capable of efficiently packaging either its 8 kilobase genome or non-viral DNA. The ability of HPV capsids to package non-viral DNA makes these a useful tool for delivering plasmids to study proteins of interest in a variety of cell types. We describe optimization of current methods and present new protocols for using HPV capsids to deliver non-viral DNA thereby providing an alternative to DNA transfection. Using keratinocyte generated extracellular matrices can enhance infection efficiency in keratinocytes, hepatocytes and neuronal cells. Furthermore, we describe a suspension-based efficient technique for infecting different cell types.

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Section: Discussionmentioning

confidence: 99%

Optimization of human papillomavirus-based pseudovirus techniques for efficient gene transfer

Gilson

Gibson

Androphy

2020

Preprint

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“…HPV infectious entry involves a complex series of steps, including the attachment of virus to the extracellular matrix, the structural remodelling of the virion, receptor attachment, endocytic uptake, intracellular trafficking through the endosomal compartment, uncoating, and the recruitment of different components of the cellular transport machinery to ensure delivery of the incoming viral genomes to the nucleus through the trans-Golgi network (25)(26)(27). However, no studies have been performed to investigate whether potential phosphorylation of the HPV capsid proteins can play any roles in any of these processes.…”

Section: Discussionmentioning

confidence: 99%

“…Interactions of the viral capsid proteins with cellular components play an important role in papillomavirus infectious entry (25)(26)(27). Intracellular processing of the viral capsid is dependent on a number of different host factors, such as furin (13), cyclophilin (16), and gamma-secretase (21,(28)(29)(30), among others.…”

mentioning

confidence: 99%

Phosphorylation of Human Papillomavirus Type 16 L2 Contributes to Efficient Virus Infectious Entry

Broniarczyk

Massimi

Pim

et al. 2019

J Virol

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The human papillomavirus (HPV) capsid comprises two viral proteins, L1 and L2, with the L2 component being essential to ensure efficient endocytic transport of incoming viral genomes. Several studies have previously reported that L1 and L2 are posttranslationally modified, but it is uncertain whether these modifications affect HPV infectious entry. Using a proteomic screen, we identified a highly conserved phospho-acceptor site on the HPV-16 and bovine papillomavirus 1 (BPV-1) L2 proteins. The phospho-modification of L2 and its presence in HPV pseudovirions (PsVs) were confirmed using anti-phospho-L2-specific antibodies. Mutation of the phosphoacceptor sites of both HPV-16 and BPV-1 L2 resulted in the production of infectious virus particles, with no differences in efficiencies of packaging the reporter DNA. However, these mutated PsVs showed marked defects in infectious entry. Further analysis revealed a defect in uncoating, characterized by a delay in the exposure of a conformational epitope on L1 that indicates capsid uncoating. This uncoating defect was accompanied by a delay in the proteolysis of both L1 and L2 in mutated HPV-16 PsVs. Taken together, these studies indicate that phosphorylation of L2 during virus assembly plays an important role in optimal uncoating of virions during infection, suggesting that phosphorylation of the viral capsid proteins contributes to infectious entry. IMPORTANCE The papillomavirus L2 capsid protein plays an essential role in infectious entry, where it directs the successful trafficking of incoming viral genomes to the nucleus. However, nothing is known about how potential posttranslational modifications may affect different aspects of capsid assembly or infectious entry. In this study, we report the first phospho-specific modification of the BPV-1 and HPV-16 L2 capsid proteins. The phospho-acceptor site is very highly conserved across multiple papillomavirus types, indicating a highly conserved function within the L2 protein and the viral capsid. We show that this modification plays an essential role in infectious entry, where it modulates susceptibility of the incoming virus to capsid disassembly. These studies therefore define a completely new means of regulating the papillomavirus L2 proteins, a regulation that optimizes endocytic processing and subsequent completion of the infectious entry pathway.

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“…During HR-HPV infection, the virus binds to the receptors on the target cell surface, resulting in its internalization, and subsequently, the viral DNA is released and transported to the cell nucleus (45,64). After the viral DNA is integrated, it synthesizes the E6 and E7 oncoproteins that promote proliferation for TP53 degradation by E6 and pRB degradation by E7; it has been observed that the degradation of pRb leads to the overexpression of OCT3/4 and that the degradation of p53 leads to an increase in the expression of NANOG (65,66), and it is well known that NANOG can directly bind to the OCT3/4 gene promoter to induce its expression (67-69).…”

Section: Oct3/4 and E6 And E7 Oncoproteinsmentioning

confidence: 99%

Role of Oct3/4 in Cervical Cancer Tumorigenesis

et al. 2020

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Cervical cancer (CC) is the fourth most common type of cancer that affects women. Compared to other types of cancer, CC has a high mortality rate in women worldwide. Several factors contribute to the development of CC, but persistent high-risk human papillomavirus infection is the main etiologic agent associated with the development of CC. Moreover, several studies reported that alterations in the expression of transcription factors present in a small subpopulation of cells within tumors called cancer stem cells (CSCs), which contribute to the development of CC by promoting tumorigenicity and metastasis. These transcription factors affect self-renewal and maintenance of pluripotency and differentiation in stem cells. OCT3/4 belongs to the family of transcription factors with the POU domain. It consists of five exons and can be edited by alternative splicing into three main transcripts: OCT3/4A, OCT3/4B, and OCT3/4B1. The OCT3/4 expression in CSCs promotes carcinogenesis and the development of malignant tumors, and the loss of expression leads to the loss of self-renewal and proliferation and favors apoptosis. This review describes the main roles of OCT3/4 in CC and its importance in several biological processes that contribute to the development of CC and may serve as molecular targets to improve prognosis of CC.

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HPV entry into cells

Cited by 73 publications

References 103 publications

Optimization of human papillomavirus-based pseudovirus techniques for efficient gene transfer

Optimization of human papillomavirus-based pseudovirus techniques for efficient gene transfer

Phosphorylation of Human Papillomavirus Type 16 L2 Contributes to Efficient Virus Infectious Entry

Role of Oct3/4 in Cervical Cancer Tumorigenesis

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