Differential binding patterns to host cells associated with particles of several human alphapapillomavirus types

Broutian, Tatevik; Brendle, Sarah A.; Christensen, Neil D.

doi:10.1099/vir.0.012732-0

Cited by 16 publications

(18 citation statements)

References 32 publications

(44 reference statements)

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“…This is likely to be laminin‐332 or an associated cofactor as indicated by the blocking experiments with antibodies or the use of laminin‐332 deficient ECM. Hence, we corroborated that HPV‐16 can, like HPV‐11 and ‐45, bind to laminin‐332 (Culp et al ., 2006b; Selinka et al ., ; Broutian et al ., ). As heparin‐preincubated virus required the presence or accessibility of laminin‐332 for infection, binding occurred via laminin‐332.…”

Section: Discussionmentioning

confidence: 97%

Heparin increases the infectivity of Human Papillomavirus Type 16 independent of cell surface proteoglycans and induces L1 epitope exposure

et al. 2013

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Summary Human Papillomaviruses (HPVs) are the etiological agents of cervical cancer, and HPV-16 is the most prevalent type. Several HPVs require heparan sulfate proteoglycans (HSPGs) for cell-binding. Here, we analyze the phenomenon that preincubation of HPV-16 with increasing concentrations of heparin results in partial restoration rather than more efficient inhibition of infection. While corroborating that the HSPGs are cell-binding receptors for HPV-16, heparin-preincubated virus bound to the extracellular matrix (ECM) via laminin-332. Furthermore, the interaction of virions with heparin, a representative of the highly sulfated S-domains of heparan sulfate (HS) chains of HSPGs, allowed HPV-16 infection in the absence of cell surface HSPGs. Therefore, we concluded that specific glycan moieties but not specific HSPG protein backbones are required for infection. The increased binding of an epitope-specific antibody to the viral capsid after heparin-binding suggested that initial conformational changes in the HPV-16 virion occur during infection by interaction with ‘heparin-like’ domains of cellular HSPGs. We propose that HS sequences with specific sulfation patterns are required to facilitate HPV-16 infection.

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Section: Discussionmentioning

confidence: 97%

Heparin increases the infectivity of Human Papillomavirus Type 16 independent of cell surface proteoglycans and induces L1 epitope exposure

et al. 2013

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“…A more accurate atomic model is needed to fully capture the structural details of inter-pentamer contacts in HPV and to better understand how surface features control antigenicity and type specificity (Chen et al, 2000; Sadeyen et al, 2003). In vitro and in a mouse model system, there is strong evidence that the HPV capsid attaches to the host cell primarily through heparan sulfate proteoglycans (HSPGs) and the non-HSPG extracellular matrix receptor, laminin-332 (formerly laminin-5), secreted by epithelial lines (Broutian et al, 2010; Culp et al, 2006a, 2006b; Giroglou et al, 2001). L1, but not L2, is the major determinant in such attachment (Roden et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

The C-Terminal Arm of the Human Papillomavirus Major Capsid Protein Is Immunogenic and Involved in Virus-Host Interaction

Yan

et al. 2016

Structure

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SUMMARY Cervical cancer is the second most prevalent malignant tumor among women worldwide. High-risk human papillomaviruses (HPVs) are believed to be the major causative pathogens of mucosal epithelial cancers including cervical cancer. The HPV capsid is made up of 360 copies of major (L1) and 72 copies of minor (L2) capsid proteins. To date, limited high-resolution structural information about the HPV capsid has hindered attempts to understand details concerning the mechanisms by which HPV assembles and infects cells. In this study, we have constructed a pseudo-atomic model of the HPV59 L1-only capsid and demonstrate that the C-terminal arm of L1 participates in virus-host interactions. Moreover, when conjugated to a scaffold protein, keyhole limpet hemocyanin (KLH), this arm is immunogenic in vivo. These results provide new insights that will help elucidate HPV biology, and hence pave a way for the design of next-generation HPV vaccines.

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“…After the virus assembles and accesses the target cells, entry of HPV16 into host cells starts with binding to heparan sulfate proteoglycans (HSPGs) that are situated within the plasma membrane or the extracellular matrix (ECM) (13)(14)(15)(16)(17)(18). Alternatively, the virus can bind to laminin-332 as a transient binding receptor (15,(19)(20)(21).…”

mentioning

confidence: 99%

“…Alternatively, the virus can bind to laminin-332 as a transient binding receptor (15,(19)(20)(21). Interaction with HSPGs facilitates a first conformational change in the virus that appears to be critical for infection (19).…”

mentioning

confidence: 99%

Kallikrein-8 Proteolytically Processes Human Papillomaviruses in the Extracellular Space To Facilitate Entry into Host Cells

Cerqueira

Ventayol

Vogeley

et al. 2015

J Virol

104

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The entry of human papillomaviruses into host cells is a complex process. It involves conformational changes at the cell surface, receptor switching, internalization by a novel endocytic mechanism, uncoating in endosomes, trafficking of a subviral complex to the Golgi complex, and nuclear entry during mitosis. Here, we addressed how the stabilizing contacts in the capsid of human papillomavirus 16 (HPV16) may be reversed to allow uncoating of the viral genome. Using biochemical and cell-biological analyses, we determined that the major capsid protein L1 underwent proteolytic cleavage during entry. In addition to a dispensable cathepsin-mediated proteolysis that occurred likely after removal of capsomers from the subviral complex in endosomes, at least two further proteolytic cleavages of L1 were observed, one of which was independent of the low-pH environment of endosomes. This cleavage occurred extracellularly. Further analysis showed that the responsible protease was the secreted trypsin-like serine protease kallikrein-8 (KLK8) involved in epidermal homeostasis and wound healing. Required for infection, the cleavage was facilitated by prior interaction of viral particles with heparan sulfate proteoglycans. KLK8-mediated cleavage was crucial for further conformational changes exposing an important epitope of the minor capsid protein L2. Occurring independently of cyclophilins and of furin that mediate L2 exposure, KLK8-mediated cleavage of L1 likely facilitated access to L2, located in the capsid lumen, and potentially uncoating. Since HPV6 and HPV18 also required KLK8 for entry, we propose that the KLK8-dependent entry step is conserved. IMPORTANCEOur analysis of the proteolytic processing of incoming HPV16, an etiological agent of cervical cancer, demonstrated that the capsid is cleaved extracellularly by a serine protease active during wound healing and that this cleavage was crucial for infection. The cleavage of L1 is one of at least four structural alterations that prime the virus extracellularly for receptor switching, internalization, and possibly uncoating. This step was also important for HPV6 and HPV18, which may suggest that it is conserved among the papillomaviruses. This study advances the understanding of how HPV16 initially infects cells, strengthens the notion that wounding facilitates infection of epidermal tissue, and may help the development of antiviral measures. Human papillomaviruses (HPVs) comprise a large family of small, nonenveloped DNA viruses with transforming potential. HPVs selectively infect basal keratinocytes of stratified skin and mucosal epithelia and persist, mostly without clinical symptoms, in virtually every part of the human skin. The biological costs of HPV persistence range from benign papilloma and genital warts over preneoplastic lesions to anogenital or oropharyngeal cancers (1). In fact, infection by the so-called "high-risk" HPV causes about 5% of all human cancers (2). Of these, cervical cancers are the most prevalent. However, HPV-associated oropharyngea...

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Differential binding patterns to host cells associated with particles of several human alphapapillomavirus types

Cited by 16 publications

References 32 publications

Heparin increases the infectivity of Human Papillomavirus Type 16 independent of cell surface proteoglycans and induces L1 epitope exposure

Heparin increases the infectivity of Human Papillomavirus Type 16 independent of cell surface proteoglycans and induces L1 epitope exposure

The C-Terminal Arm of the Human Papillomavirus Major Capsid Protein Is Immunogenic and Involved in Virus-Host Interaction

Kallikrein-8 Proteolytically Processes Human Papillomaviruses in the Extracellular Space To Facilitate Entry into Host Cells

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