HPV virions hitchhike a ride on retromer complexes

Sapp, Martin

doi:10.1073/pnas.1305245110

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…This interaction with the host cell induces conformational changes in both capsid proteins and cleavage of the inner virion protein L2, which allows virus transfer to a secondary receptor complex (Evander et al, 1997;Richards et al, 2006;Selinka et al, 2007;Bienkowska-Haba et al, 2009b;Surviladze et al, 2012;Woodham et al, 2012;Cerqueira et al, 2013). Cell entry of HPV16 is facilitated by a clathrin-, caveolinand dynamin-independent but tetraspanin-and actindependent endocytosis pathway (Spoden et al, 2008;2013;Schelhaas et al, 2012;Scheffer et al, 2013). After cell entry, intracellular trafficking through endosomal and Golgi compartments leads to capsid disassembly and release of the L2/HPV genome complex (Bienkowska-Haba et al, 2009b;Cerqueira and Schelhaas, 2012;Florin et al, 2012;Day et al, 2013;Lipovsky et al, 2013;Sapp, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Cell entry of HPV16 is facilitated by a clathrin-, caveolinand dynamin-independent but tetraspanin-and actindependent endocytosis pathway (Spoden et al, 2008;2013;Schelhaas et al, 2012;Scheffer et al, 2013). After cell entry, intracellular trafficking through endosomal and Golgi compartments leads to capsid disassembly and release of the L2/HPV genome complex (Bienkowska-Haba et al, 2009b;Cerqueira and Schelhaas, 2012;Florin et al, 2012;Day et al, 2013;Lipovsky et al, 2013;Sapp, 2013). The minor capsid protein L2 chaperones the viral genome into the nucleus and accumulates at subnuclear foci, the PML nuclear bodies (PML-NBs) (Day et al, 1998;Florin et al, 2002a) leading to manifestation of infection, stimulation of cell proliferation, vegetative amplification of the genome, and, finally, viral morphogenesis (Chiang et al, 1992;Florin et al, 2002a;Becker et al, 2004;Day et al, 2004;Doorbar, 2005;Munger et al, 2006;Graham, 2008;Schwartz, 2008).…”

Section: Introductionmentioning

confidence: 99%

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An L2 SUMO interacting motif is important for PML localization and infection of human papillomavirus type 16

et al. 2014

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SummaryHuman papillomaviruses (HPV) induce warts and cancers on skin and mucosa. The HPV16 capsid is composed of the proteins L1 and L2. After cell entry and virus disassembly, the L2 protein accompanies the viral DNA to promyelocytic leukaemia nuclear bodies (PML-NBs) within the host nuclei enabling viral transcription and replication. Multiple components of PML-NBs are regulated by small ubiquitin-like modifiers (SUMOs) either based on covalent SUMO modification (SUMOylation), or based on non-covalent SUMO interaction via SUMO interacting motifs (SIMs). We show here that the HPV16 L2 comprises at least one SIM, which is crucial for the L2 interaction with SUMO2 in immunoprecipitation and colocalization with SUMO2 in PML-NBs. Biophysical analysis confirmed a direct L2 interaction with SUMO substantiated by identification of potential L2-SUMO interaction structures in molecular dynamics simulations. Mutation of the SIM resulted in absence of the L2-DNA complex at PML-NB and in a loss of infectivity of mutant HPV16 pseudoviruses. In contrast, we found that L2 SUMOylation has no effect on L2 localization in PML-NBs and SUMO interaction. Our data suggest that the L2 SIM is important for L2 interaction with SUMO and/or SUMOylated proteins, which is indispensable for the delivery of viral DNA to PML-NBs and efficient HPV infection.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An L2 SUMO interacting motif is important for PML localization and infection of human papillomavirus type 16

et al. 2014

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“…The basal layer contains the long-lived keratinocyte stem cells and is the only location in the normal epithelium where cell division is known to occur 31 . Following cell entry 32,33 , the virus undergoes genome replication to establish a stable pool of episomal viral genomes. Overall viral gene expression is suppressed.…”

Section: The Hpv Life Cyclementioning

confidence: 99%

The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

Woodby

Scott

Bodily

2016

Progress in Molecular Biology and Translational Science

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Human papillomaviruses (HPV) are small, double-stranded DNA viruses that replicate in stratified squamous epithelia and cause a variety of malignancies. Current efforts in HPV biology are focused on understanding the virus-host interactions that enable HPV to persist for years or decades in the tissue. The importance of interactions between tumor cells and the stromal microenvironment has become increasingly apparent in recent years, but how stromal interactions impact the normal, benign life cycle of HPVs or progression of lesions to cancer is less understood. Furthermore, how productively replicating HPV impacts cells in the stromal environment is also unclear. Here we bring together some of the relevant literature on keratinocyte-stromal interactions and their impacts on HPV biology. We discuss how HPV oncogenes in infected cells manipulate other cells in their environment, and, conversely, how neighboring cells may impact the efficiency or course of HPV infection.

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“…HPV is a non-enveloped double-stranded DNA virus containing two major capsid proteins (L1 and L2) that function in cooperative fashion to mediate viral entry into host cells (Fig. 3B) (Lipovsky et al, 2013;Sapp, 2013). The virus is taken up into the cell through a process known as "micropinocytosis" (Schelhaas et al, 2012).…”

Section: Cargo Name Notation Function Referencesmentioning

confidence: 99%

“…The logical analysis of these results leads to the theory that L2 proteins directly interact with retromer CRCs, likely by penetrating the endosomal membrane, though it is also possible that L2 interacts with a receptor that is then bound by the retromer (Fig. 3B) (Popa et al, 2015;Sapp, 2013). Both HIV-1 and HPV appear to hijack the retromer complex and its recycling pathway for the ultimate gain of the virus.…”

Section: Cargo Name Notation Function Referencesmentioning

confidence: 99%