PYHIN Proteins and HPV: Role in the Pathogenesis of Head and Neck Squamous Cell Carcinoma

Riva, Giuseppe; Biolatti, Matteo; Pecorari, Giancarlo; Dell’Oste, Valentina; Landolfo, Santo

doi:10.3390/microorganisms8010014

Cited by 15 publications

(7 citation statements)

References 89 publications

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“…These chemokine responses may also be detrimental to HPV persistence, as evidenced by a recent mouse papillomavirus study where MmuPV1 was observed to specifically downregulate stress keratin-induced expression of CXCR3 ligands including CXCL10 [ 108 ]. IFI16 is a DNA-binding inflammasome component and can restrict HPV replication by epigenetically silencing viral gene expression reducing vDNA copy number [ 109 , 110 ]. Several of the genes upregulated by dsDNA transfection are counteracted by papillomavirus gene products.…”

Section: Discussionmentioning

confidence: 99%

Vesicular trafficking permits evasion of cGAS/STING surveillance during initial human papillomavirus infection

Uhlorn

Jackson

et al. 2020

PLoS Pathog

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Oncogenic human papillomaviruses (HPVs) replicate in differentiating epithelium, causing 5% of cancers worldwide. Like most other DNA viruses, HPV infection initiates after trafficking viral genome (vDNA) to host cell nuclei. Cells possess innate surveillance pathways to detect microbial components or physiological stresses often associated with microbial infections. One of these pathways, cGAS/STING, induces IRF3-dependent antiviral interferon (IFN) responses upon detection of cytosolic DNA. Virion-associated vDNA can activate cGAS/STING during initial viral entry and uncoating/trafficking, and thus cGAS/STING is an obstacle to many DNA viruses. HPV has a unique vesicular trafficking pathway compared to many other DNA viruses. As the capsid uncoats within acidic endosomal compartments, minor capsid protein L2 protrudes across vesicular membranes to facilitate transport of vDNA to the Golgi. L2/vDNA resides within the Golgi lumen until G2/M, whereupon vesicular L2/vDNA traffics along spindle microtubules, tethering to chromosomes to access daughter cell nuclei. L2/vDNA-containing vesicles likely remain intact until G1, following nuclear envelope reformation. We hypothesize that this unique vesicular trafficking protects HPV from cGAS/STING surveillance. Here, we investigate cGAS/STING responses to HPV infection. DNA transfection resulted in acute cGAS/STING activation and downstream IFN responses. In contrast, HPV infection elicited minimal cGAS/STING and IFN responses. To determine the role of vesicular trafficking in cGAS/STING evasion, we forced premature viral penetration of vesicular membranes with membrane-perturbing cationic lipids. Such treatment renders a non-infectious trafficking-defective mutant HPV infectious, yet susceptible to cGAS/STING detection. Overall, HPV evades cGAS/STING by its unique subcellular trafficking, a property that may contribute to establishment of infection.

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Section: Discussionmentioning

confidence: 99%

Vesicular trafficking permits evasion of cGAS/STING surveillance during initial human papillomavirus infection

Uhlorn

Jackson

et al. 2020

PLoS Pathog

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“…Another difference between HPV - and HPV + HNSCCs lies in expression of the two PYHIN proteins IFI16 and AIM2, the former nuclear and the second cytoplasmic sensors of double strand (ds) DNA. More specifically, while IFI16 is generally upregulated in HPV + HNSCC, AIM2 gene expression levels are usually found unchanged in HPV + HNSCCs with respect to their HPV - counterparts, where this gene is already expressed at high levels (10% vs. 50% of cases, respectively) [ 12 , 13 ].…”

Section: Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

“…In addition, APOBEC3B (A3B) has been involved in HPV + HNSCC mutagenesis [ 11 ]. Intriguingly, diminished exposure to exogenous carcinogens tends to favor APOBEC-mediated mutations of HPV + HNSCC, whereas HPV - HNSCC mostly retains a carcinogen-associated mutational profile [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

HPV Meets APOBEC: New Players in Head and Neck Cancer

Riva

Albano

Gugliesi

et al. 2021

IJMS

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Besides smoking and alcohol, human papillomavirus (HPV) is a factor promoting head and neck squamous cell carcinoma (HNSCC). In some human tumors, including HNSCC, a number of mutations are caused by aberrantly activated DNA-modifying enzymes, such as the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) family of cytidine deaminases. As the enzymatic activity of APOBEC proteins contributes to the innate immune response to viruses, including HPV, the role of APOBEC proteins in HPV-driven head and neck carcinogenesis has recently gained increasing attention. Ongoing research efforts take the cue from two key observations: (1) APOBEC expression depends on HPV infection status in HNSCC; and (2) APOBEC activity plays a major role in HPV-positive HNSCC mutagenesis. This review focuses on recent advances on the role of APOBEC proteins in HPV-positive vs. HPV-negative HNSCC.

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“…Tobacco, and betel nut use and genetic susceptibility are currently recognized worldwide as major HNSCC risk factors [3]. Moreover, human papillomavirus (HPV)-speci c subgroup infection (HPV16, HPV18) and dynamic change of the oral microbiome are also considered HNSCC promoting factors [5][6][7]. However, HNSCC pathogenesis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Application of weighted gene co-expression network analysis to explore potential prognostic markers of head and neck squamous cell carcinoma

Zeng

Gao

et al. 2022

Preprint

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Currently, there are no specific head and neck squamous cell carcinoma (HNSCC) prognostic markers. We explored the potential HNSCC prognostic markers using weighted gene co-expression network analysis (WGCNA). We obtained raw datasets of HNSCC and matched normal mucosal tissues and screened out differentially expressed genes (DEGs), then analyzed DEG enrichment. DEG co-expression network modules for both tumor and normal tissues were constructed using WGCNA, then hub genes in tumor set-specific modules were selected. Key genes underwent survival analysis using the HNSCC dataset in The Cancer Genome Atlas database. The key gene expression profiles in the clinical samples were verified with RT-qPCR and western blotting. We identified 893 DEGs: 518 were upregulated (mainly distributed in the exogenous metabolic processes, epidermal development, regulation of inflammatory mediators of TRP channels, and tyrosine metabolism) and 375 were downregulated (mainly related to cell adhesion, osteoblast and adipocyte lipolysis regulation, and the RIG-I-like receptor signaling pathway). The WGCNA constructs of the HNSCC co-expression module uncovered 10 hub genes. Survival analysis determined that EOMES (eomesodermin) and SPRYD3 (SPRYD domain-containing protein 3) were closely related to HNSCC prognosis and differentially expressed in oral cancer clinical tissues. EOMES and SPRYD3 might be potential HNSCC prognostic markers and therapeutic targets.

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PYHIN Proteins and HPV: Role in the Pathogenesis of Head and Neck Squamous Cell Carcinoma

Cited by 15 publications

References 89 publications

Vesicular trafficking permits evasion of cGAS/STING surveillance during initial human papillomavirus infection

Vesicular trafficking permits evasion of cGAS/STING surveillance during initial human papillomavirus infection

HPV Meets APOBEC: New Players in Head and Neck Cancer

Application of weighted gene co-expression network analysis to explore potential prognostic markers of head and neck squamous cell carcinoma

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