• tumour virus infections
• oncogenes

• Humans
• Neoplasms/virology
• Neoplasms/therapy
• Neoplasms/genetics
• Neoplasms/pathology
• Oncogenic Viruses/pathogenicity
• Oncogenic Viruses/genetics
• Carcinogenesis/genetics
• Tumor Virus Infections/virology
• Tumor Virus Infections/genetics
• Herpesvirus 4, Human/pathogenicity

• This study was supported by the Chongqing Science and Health Joint Medical Research Sprint, Key Projects, and Major Projects (2025DBXM002), Chongqing Innovative Medical Device Application Demonstration Project (CQEIC2024MDAD-050), the Key Project of Chongqing Technology Innovation and Application Development Special Project (CSTB2024TIAD-KPX0031), National Natural Science Foundation of China (82370114), Special Project for Performance Incentive Guidance of Scientific Research Institutions (2024JXJL-YFX0022), Natural Science Foundation of Chongqing, China (CSTB2022NSCQ-MSX1150), the Fundamental Research Funds for the Central Universities (2022CDJYGRH-001) and the Chongqing Professional Talents Plan (cstc2022ycjh-bgzxm0048).

• cell type
• diversity
• ecology
• evolution
• genotype-to-phenotype
• infection and cancer
• microbiote
• papillomavirus
• phenotype
• phenotype-to-environment
• virome
• virus–host interactions

• Humans
• Papillomavirus Infections/virology
• Microbiota
• Neoplasms/virology
• Human papillomavirus 16/genetics
• Human papillomavirus 16/physiology
• Human papillomavirus 16/pathogenicity
• Papillomaviridae/physiology
• Papillomaviridae/genetics

• ERC-CoG-647916 European Union
• Fondation pour la Recherche Médicale

• CRPV
• HNSCC
• cottontail rabbit papillomavirus
• head and neck cancer
• head and neck squamous cell carcinoma
• rabbit
• tumor model

• Animals
• Humans
• Rabbits
• Carcinoma, Squamous Cell/virology
• Carcinoma, Squamous Cell/veterinary
• Cottontail rabbit papillomavirus/genetics
• Cottontail rabbit papillomavirus/pathogenicity
• Disease Models, Animal
• Head and Neck Neoplasms/virology
• Papillomavirus Infections/virology
• Papillomavirus Infections/veterinary
• Squamous Cell Carcinoma of Head and Neck/virology

• cervical cancer
• cervical lesions
• detection methods
• human papillomavirus

• Animals
• Rabbits
• Cottontail rabbit papillomavirus/genetics
• Papillomavirus Infections/virology
• Papillomavirus Infections/genetics
• Papillomavirus Infections/metabolism
• Promoter Regions, Genetic
• Skin Neoplasms/virology
• Skin Neoplasms/genetics
• Skin Neoplasms/pathology
• Transcription, Genetic
• Genome, Viral
• RNA, Viral/genetics
• RNA, Viral/metabolism

• R01 CA047622 NCI NIH HHS
• ZIA SC010357 Intramural NIH HHS
• National Cancer Institute, NIH
• National Institutes of Health
• China Scholarship Council

• HPV
• HPV-related cancers
• cervical cancer
• co-infection
• microbiome
• viral pathogens

• Female
• Humans
• Papillomavirus Infections/complications
• Coinfection
• Epstein-Barr Virus Infections
• Herpesvirus 4, Human
• Neoplasms/complications
• Papillomaviridae

• CRPV
• E6
• E7
• HNSCC
• RNAi
• VX2 carcinoma
• head and neck cancer
• lipopolyplexes
• papillomavirus

• HR-HPV
• human immunodeficiency virus
• human papillomavirus
• sub-Saharan Africa

• Cottontail rabbit papillomavirus
• Human papillomavirus
• Notch signaling pathway

Approximately 5% of all human cancers are attributable to human papillomavirus (HPV) infections. HPV-associated diseases and cancers remain a substantial public health and economic burden worldwide despite the availability of prophylactic HPV vaccines. Current diagnosis and treatments for HPV-associated diseases and cancers are predominantly based on cell/tissue morphological examination and/or testing for the presence of high-risk HPV types. There is a lack of robust targets/markers to improve the accuracy of diagnosis and treatments. Several naturally occurring animal papillomavirus models have been established as surrogates to study HPV pathogenesis. Among them, the Cottontail rabbit papillomavirus (CRPV) model has become known as the gold standard. This model has played a pivotal role in the successful development of vaccines now available to prevent HPV infections. Over the past eighty years, the CRPV model has been widely applied to study HPV carcinogenesis. Taking advantage of a large panel of functional mutant CRPV genomes with distinct, reproducible, and predictable phenotypes, we have gained a deeper understanding of viral–host interaction during tumor progression. In recent years, the application of genome-wide RNA-seq analysis to the CRPV model has allowed us to learn and validate changes that parallel those reported in HPV-associated cancers. In addition, we have established a selection of gene-modified rabbit lines to facilitate mechanistic studies and the development of novel therapeutic strategies. In the current review, we summarize some significant findings that have advanced our understanding of HPV pathogenesis and highlight the implication of the development of novel gene-modified rabbits to future mechanistic studies.

• CRPV
• HPV
• RNAseq
• cancer
• codon optimization
• disease progression
• gene modified rabbits
• immune responses
• papillomavirus
• rabbit
• tumor regression
• wound healing

Bone cement is a crucial material to treat bone metastases defects, and can fill the bone defect and provide mechanical support simultaneously, but the antitumor effect is very limited. Magnetic bone cement not only supports bone metastasis defects but can also achieve magnetic hyperthermia to eliminate tumor cells around the bone defect. However, the physicochemical properties of the bone cement matrix will change if the weight ratio of the magnetic nanoparticles in the cement is too high. We mixed 1 weight percent Zn_0.3Fe_2.7O₄ with good biocompatibility and high heating efficiency into a polymethyl methacrylate matrix to prepare magnetic bone cement, which minimized the affection for physicochemical properties and satisfied the hyperthermia requirement of the alternating magnetic field.

Malignant central airway stenosis is a life-threatening condition. However, treatment of malignant airway stenosis remains challenging. There is currently a severe lack of an excellent animal model of malignant airway stenosis to facilitate treatment approaches. This is the first study to establish a rabbit model of malignant airway stenosis for bronchoscopic interventional studies.

New Zealand White rabbits were used in this study, randomly divided into group A (18 rabbits) and group B (6 rabbits). A VX2 fragment suspension was injected into the submucosal layer of rabbits’ airway by bronchoscopy. Bronchoscopic examinations were performed once a week after VX2 tumor implantation to observe tumor growth and the degree of airway stenosis. Randomly, three rabbits were generally dissected after a weekly bronchoscopic examination in group A. The rabbits that reached grade III airway stenosis underwent stent implantation in group B.

A total of 24 rabbits were successfully implanted with the VX2 fragment suspension in the airway without significant adverse events, and the success rate of the tumor growth was 100%. The degree of airway stenosis reaching grade III took 2 to 3 weeks after implantation of the VX2 tumor. The median survival time of rabbit models without stent implantation and rabbits with stent implantation was 32.5 and 32.0 days, respectively.

The implanting method is safe and effective for the establishment of a rabbit model of malignant airway stenosis. When the tumor grows to 2 to 3 weeks, the rabbit model is available for stent implantation. We recommend the models for more preclinical animal studies on bronchoscopic interventional treatments.

• Lgr5
• cell of origin
• mouse papillomavirus

• Animals
• Carcinoma, Squamous Cell/etiology
• Humans
• Mice
• Mice, Transgenic
• Papillomaviridae
• Receptors, G-Protein-Coupled
• Skin Neoplasms
• Stem Cells

• P01 CA022443 NCI NIH HHS
• R35 CA210807 NCI NIH HHS

• Animal models
• DNA tumor Viruses
• Human papillomaviruses
• Infection models
• Merkel cell polyomavirus

High-risk human papillomavirus (HPV) infections induce squamous epithelial tumors in which the virus replicates. Initially, the virus-infected cells are untransformed, but expand in both number and area at the expense of uninfected squamous epithelial cells. We have developed an in vitro assay in which colonies of post-confluent HPV16 expressing cells outcompete and displace confluent surrounding uninfected keratinocytes. The enhanced colony competition induced by the complete HPV16 genome is conferred by E6 expression alone, not by individual expression of E5 or E7, and requires E6 interaction with p53. E6-expressing keratinocytes undermine and displace adjacent normal keratinocytes from contact with the attachment substrate, thereby expanding the area of the E6-expressing colony at the expense of normal keratinocytes. These new results separate classic oncogenicity that is primarily conferred by HPV16 E7 from cell competition that we show is primarily conferred by E6 and provides a new biological role for E6 oncoproteins from high-risk human papillomaviruses.

Microbial infections can change the fate and behavior of normal vertebrate cells to resemble oncogenic cells. High-risk papillomaviruses induce infected squamous epithelial cells to form tumors, some of which evolve into malignancies. The present work shows that the enhanced competitiveness of HPV16-infected cells for the basal cell surface is primarily due to the expression of the E6 oncoprotein and not the E7 or E5 oncoproteins. Compared to normal keratinocytes, E6 induces a super-competitor phenotype while E5 and E7 do not. This work shows the importance of measuring oncoprotein traits not only as cell autonomous traits, but in the context of competition with uninfected cells and shows the potential of papillomavirus oncoproteins to be novel genetic probes for the analysis of cell competition.

• Cell Competition
• Human papillomavirus 16/genetics
• Human papillomavirus 16/metabolism
• Humans
• Keratinocytes
• Oncogene Proteins, Viral/genetics
• Oncogene Proteins, Viral/metabolism
• Papillomavirus E7 Proteins/genetics
• Papillomavirus E7 Proteins/metabolism
• Papillomavirus Infections/genetics
• Repressor Proteins/genetics
• Repressor Proteins/metabolism

• R01 AI158426 NIAID NIH HHS
• R01 CA134737 NCI NIH HHS
• Division of Cancer Epidemiology and Genetics, National Cancer Institute
• National Institute of Allergy and Infectious Diseases
• University of Virginia

Infection is currently one of the main contributors to carcinogenesis. In fact, the International Agency for Research on Cancer has categorized eleven biological agents as group I carcinogens. It is estimated that around 16% of the 12.7 million new cancers diagnosed in 2008 were attributable to infectious agents. Although underdeveloped regions carry the highest incidence rates, about 7.4% of infection-related cancer cases occur in developed areas. Physicians are increasingly aware of the potential carcinogenic role of common virus like the Human Papilloma virus in cervical cancer, or the hepatitis B and C viruses in hepatocarcinoma. However, the carcinogenic role of several other infectious agents is less recognized. Given that gastrointestinal malignancies carry an overall poor prognosis, a better understanding of the carcinogenic mechanisms triggered by infectious agents is key to decrease the rate of cancer related deaths. Preventive measures directed to such infections would ideally impact survival. In this paper we review the main pathogenic mechanisms related to the development of gastrointestinal malignancies induced by infectious microorganisms and other pathogens which are currently under investigation.

• Gastrointestinal tumors
• Infectious agents
• Bacteria
• Virus
• Prevention

Introduction: TheraSphere^® microspheres containing yttrium ⁹⁰Y are among many radioembolization agents used clinically to reduce liver tumor burden, and their effects on cancer volume reduction are well-established. At the same time, concerns about off target tissue injury often limit their use. Deeper investigation into tissue distribution and long-term impact of these microspheres could inform us about additional ways to use them in practice.

Methods: Healthy rat liver and rabbit liver tumor samples from animals treated with TheraSpheres were sectioned and their elemental maps were generated by X-ray fluorescence microscopy (XFM) at the Advanced Photon Source (APS) synchrotron at Argonne National Laboratory (ANL).

Results: Elemental imaging allowed us to identify the presence and distribution of TheraSpheres in animal tissues without the need for additional sample manipulation or staining. Ionizing radiation produced by ⁹⁰Y radioactive contaminants present in these microspheres makes processing TheraSphere treated samples complex. Accumulation of microspheres in macrophages was observed.

Conclusions: This is the first study that used XFM to evaluate the location of microspheres and radionuclides in animal liver and tumor samples introduced through radioembolization. XFM has shown promise in expanding our understanding of radioembolization and could be used for investigation of human patient samples in the future.

• X-ray fluorescence microscopy
• hepatocellular carcinoma
• rabbit (Lagomorph)
• radioembolization of liver malignancies
• yttrium 90 microspheres

• CD28
• HPV
• T cell
• cutaneous horn
• immunodeficiency
• oncogene
• papillomavirus
• somatic reversion
• tree man syndrome
• wart

• Adult
• Amino Acid Sequence
• Animals
• Base Sequence
• CD28 Antigens/deficiency
• CD28 Antigens/genetics
• CD28 Antigens/metabolism
• CD4-Positive T-Lymphocytes/immunology
• Child
• Endopeptidases/metabolism
• Female
• Genes, Recessive
• HEK293 Cells
• Homozygote
• Humans
• Immunity, Humoral
• Immunologic Memory
• Inheritance Patterns/genetics
• Jurkat Cells
• Keratinocytes/pathology
• Male
• Mice, Inbred C57BL
• Oncogenes
• Papilloma/pathology
• Papilloma/virology
• Papillomaviridae/physiology
• Pedigree
• Protein Sorting Signals
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Skin/virology
• T-Lymphocytes/immunology
• Mice

• MC_U117584278 Medical Research Council
• 28754 Cancer Research UK
• MC_PC_13050 Medical Research Council
• U19 AI057229 NIAID NIH HHS
• UL1 TR001866 NCATS NIH HHS
• MR/S024409/1 Medical Research Council
• R01 AI143810 NIAID NIH HHS

• cervical cancer
• human papillomavirus (HPV)
• low- and middle- income countries (LMIC)
• prophylactic vaccines

• Alphapapillomavirus/drug effects
• Alphapapillomavirus/metabolism
• Alphapapillomavirus/pathogenicity
• Female
• Furin/metabolism
• Heparan Sulfate Proteoglycans/metabolism
• Host-Pathogen Interactions/drug effects
• Host-Pathogen Interactions/physiology
• Humans
• Molecular Targeted Therapy/methods
• Papillomavirus Infections/etiology
• Papillomavirus Infections/prevention & control
• Polysaccharides/chemistry
• Polysaccharides/pharmacology

• research grant Cancer Association of South Africa
• TMA2018SF-2446 European and Developing Countries Clinical Trials Partnership
• 104837 National Research Foundation
• 105887 National Research Foundation
• 18/21 Poliomyelitis Research Foundation

Establishing the efficacy of novel photosensitizers (PSs) for phototherapy of lung cancer requires in vivo study prior to clinical evaluation. However, previously described animal models are not ideal for assessing transbronchial approaches with such PSs.

An ultra-small parallel-type composite optical fiberscope (COF) with a 0.97 mm outer diameter tip. The integration of illumination and laser irradiation fibers inside the COF allows simultaneous white-light and fluorescence imaging, as well as real-time monitoring of tip position during laser phototherapy. An orthotopic lung cancer mouse model was created with three human lung cancer cell lines transbronchially inoculated into athymic nude mice. The COF was inserted transbronchially into a total of 15 mice for tumor observation. For in vivo fluorescence imaging, an organic nanoparticle, porphysome, was used as a PS. Laser excitation through the COF was performed at 50 mW using a 671 nm source.

The overall success rate for creating orthotopic lung tumors was 71%. Transbronchial white light images were successfully captured by COF. Access to the left main bronchus was successful in 87% of mice (13/15), the right main bronchus to the cranial lobe bronchus level in 100% (15/15), and to the right basal trifurcation of the middle lobe, caudal lobe and accessory lobe in 93% (14/15). For transbronchial tumor localization of orthotopic lung cancer tumors, PS-laden tumor with the strong signal was clearly contrasted from the normal bronchial wall.

The ultra-small COF enabled reliable transbronchial access to orthotopic human lung cancer xenografts in vivo. This method could serve as a versatile preclinical research platform for PS evaluation in lung cancer, enabling transbronchial approaches in in vivo survival models inoculated with human lung cancer cells.

• Fluorescence imaging
• bronchoscopy
• lung cancer
• orthotopic lung cancer mouse model
• photosensitizer

• Bos taurus papillomavirus
• anal fibropapilloma
• anogenital neoplasms
• anogenital papillomavirus
• bovine papillomavirus
• vulval papilloma

Although, there is a variable burden of human papillomavirus (HPV) in women infected with HIV in developing countries, there are few studies that attempted to surmise such variable evidences. This review aimed to estimate the pooled prevalence of HPV genotype distribution and risk factors contributing to HPV infection among women infected with HIV in low- and middle-income countries.

We conducted a systematic review and meta-analysis of studies conducted in developing countries and reported HPV prevalence. We searched electronic databases: PubMed/Medline, SCOPUS, ScienceDirect, Excerpta Medical Database from Elsevier, Web of science, Cumulative Index of Nursing and allied Health Sciences and Google scholar databases to retrieve primary studies published in English language till 11th August 2019. We used random-effects model to estimate the pooled prevalence of HPV genotypes, and funnel plot to assess publication bias. The registration number of this review study protocol is CRD42019123549.

We included nineteen studies with a total of 8,175 participants in this review. The prevalence of HPV was extremely heterogeneous across the studies (χ²₌ 3782.80, p value < 0.001, I² = 99.6%). The estimated pooled prevalence of all HPV genotypes was 63.0% (95% CI: 48.0–78.0) while the pooled prevalence of high risk and low risk HPV genotypes were 51.0% (95% CI: 38.0–63.0) and 28.0% (95% CI: 12.0–43.0), respectively. The pooled prevalence of HPV genotype 16 was 20%, while genotype 18 and 52 were 15% and 13%, respectively. Different risk factors reported for HPV infection and the frequently reported were low CD4 count below 200 cells/mm³ and high HIV viral load.

The pooled prevalence of HPV among HIV infected women in low- and middle-income countries was considerable and the proportion of high risk HPV genotypes were high when compared with low risk genotypes. Therefore, it is essential for the HPV prevention program to prevent the double burden of HPV and HIV in women.

• Developing countries
• Genotype
• Human immunodeficiency virus
• Human papillomavirus
• Meta-analysis
• Women/females

Globally, the burden of papilloma virus-associated cancers is high. About 5% of all cancers worldwide are caused by the human papillomavirus (HPV). Photodynamic therapy (PDT) is considered as a useful therapeutic option to treat cancers, particularly those near the tissue surface, since it is typically well tolerated and less invasive with a lower risk of severe complications as compared to conventional treatment strategies. PDT requires the combination of a photosensitizer, light of a specific wavelength, and tissue oxygen. In the present study, we examined the effectiveness of PDT together with a curcumin (liposome)-based photosensitizer in three papilloma virus-associated cell lines. PDT with curcumin liposomes could inhibit proliferation, cell migration, and colony formation of the tested tumor cells. The results suggest that curcumin-encapsulated liposomes in conjunction with PDT could be a useful tool for the treatment of papilloma virus-associated tumors.

Photodynamic therapy (PDT) is a minimally invasive therapeutic approach used in the treatment of various medical conditions and cancerous diseases, involving light, a photosensitizing substance, and oxygen. Curcumin, a naturally occurring compound, carries antitumor activities and potentially could be exploited as a photosensitizer in PDT. Only little is known about liposomal-encapsulated curcumin that could help in increasing the efficacy, stability, and bioavailability of this compound. This study investigates the in vitro effects of curcumin-loaded liposomes in combination with PDT. Three papilloma virus-associated cell lines were treated with curcumin-loaded liposomes corresponding to a curcumin concentration of 0–100 µmol/L for 4 h followed by illumination at 457 nm (blue) for 45, 136, and 227 s at a fluence of 220.2 W/m² (100 mA) corresponding to 1, 3 and 5 J·cm⁻². After 24 h, the biological outcome of the treatment was assessed with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), SYTO9/PI (propidium iodide), Annexin V-FITC (fluorescein isothiocyanate)/PI, clonogenic survival, and scratch (wound closure) assays. Photoactivation of curcumin-loaded liposomes led to a significant reduction in colony formation and migratory abilities, as well as to an increase in tumor cell death. The results point to the combination of curcumin-loaded liposomes with PDT as a potentially useful tool for the treatment of papillomavirus-associated malignancies.

• cervical cancer
• curcumin liposomes
• head and neck cancer
• head and neck squamous cell carcinoma (HNSCC)
• papilloma virus
• photodynamic therapy

• bovine
• oncoproteins
• papillomavirus
• review
• species-specific

Since its first discovery as part of the Rous sarcoma virus (RSV) genome, the c-SRC (SRC) proto-oncogene has been proved a key regulator of cancer development and progression, and thus it has been highlighted as an attractive target for anti-cancer therapeutic strategies. Though the exact mechanisms of its action are still not fully understood, SRC protein mediates crucial normal cell functions, such as cell development, proliferation and survival, and its dysregulation is considered as an oncogenic signature and a driving force for cancer initiation. In the present review, we present a flashback to the history of the Src research, while focusing on the most important milestones in the field. Moreover, we investigate the proposed regulatory mechanisms and molecules that mediate its action in order to designate putative therapeutic targets and useful prognostic and/or diagnostic tools. Furthermore, we present and discuss existing therapeutic approaches that are explored in clinical settings.

• Rous sarcoma virus
• Src oncogene
• cancer therapy
• carcinogenesis
• miRNAs

• MmuPV1
• animal models
• human papillomavirus
• murine papillomavirus
• papillomavirus
• viral oncology
• viral pathogenesis

• Animals
• Carcinogenesis
• Disease Models, Animal
• Mice
• Papillomaviridae/metabolism
• Papillomaviridae/pathogenicity
• Papillomavirus Infections/veterinary
• Papillomavirus Infections/virology

• P50 DE026787 NIDCR NIH HHS
• R50 CA211246 NCI NIH HHS
• R01 CA228543 NCI NIH HHS
• R35 CA210807 NCI NIH HHS
• P01 CA022443 NCI NIH HHS
• HHS | National Institutes of Health (NIH)

• DNA vaccine
• anti-viral treatment
• immunization
• infection
• papillomavirus
• rabbit

• HPV
• Rab5
• Rab6A
• Rab7
• Rab9A
• epithelial biology
• virus entry
• virus infection

• R01 CA207368 NCI NIH HHS
• T32 AI007538 NIAID NIH HHS

• genetic diversity
• human and wildlife cancer
• inbreeding
• oncogenic mutations
• oncogenic pathogens

Background: Minimally invasive modalities are of great interest in the field of treating bone tumors. However, providing reliable mechanical support and fast killing of tumor cells to achieve rapid recovery of physical function is still challenging in clinical works.

Methods: A material with two functions, mechanical support and magnetic thermal ablation, was developed from Fe₃O₄ nanoparticles (NPs) distributed in a polymethylmethacrylate (PMMA) bone cement. The mechanical properties and efficiency of magnetic field-induced thermal ablation were systematically and successfully evaluated in vitro and ex vivo. CT images and pathological examination were successfully applied to evaluate therapeutic efficacy with a rabbit bone tumor model. Biosafety evaluation was performed with a rabbit in vivo, and a cytotoxicity test was performed in vitro.

Results: An NP content of 6% Fe₃O₄ (PMMA-6% Fe₃O₄, m_Fe: 0.01 g) gave the most suitable performance for in vivo study. At the 56-day follow-up after treatment, bone tumors were ablated without obvious side effects. The pathological examination and new bone formation in CT images clearly illustrate that the bone tumors were completely eliminated. Correspondingly, after treatment, the tendency of bone tumors toward metastasis significantly decreased. Moreover, with well-designed mechanical properties, PMMA-6%Fe₃O₄ implantation endowed tumor-bearing rabbit legs with excellent bio-mimic bone structure and internal support. Biosafety evaluation did not induce an increase or decrease in the immune response, and major functional parameters were all at normal levels.

Conclusion: We have presented a novel, highly efficient and minimally invasive approach for complete bone tumor regression and bone defect repair by magnetic thermal ablation based on PMMA containing Fe₃O₄ NPs; this approach shows excellent heating ability for rabbit VX2 tibial plateau tumor ablation upon exposure to an alternating magnetic field (AMF) and provides mechanical support for bone repair. The new and powerful dual-function implant is a promising minimally invasive agent for the treatment of bone tumors and has good clinical translation potential.

• PMMA
• bone tumors
• magnetic thermal ablation
• mechanical support, fast clinical translation

• cancer
• molecular biology
• tumor viruses

Human papillomaviruses (HPVs), like all PVs, predominantly cause benign tumors, or warts, in stratifying squamous epithelial tissues. Virions are released from apical surfaces of the skin and mucosa and, to initiate a new infection, must utilize a break in the epithelial barrier to access mitotically active basal epithelial cells. Laboratory models currently used to study the HPV infectious process reveal that heparan sulfate proteoglycans and cellular enzymes are utilized to prime virions and activate cell signaling to coordinate virus association with a receptor complex for uptake into keratinocytes. Conventional cell-based infection systems lack many aspects relevant to determining the role of epithelial wounding in HPV infections. Nevertheless, many cellular factors involved in virion interaction with cells have been shown to actively coordinate their activities in the dynamic state of an epithelial wound. In this review, I summarize the current knowledge regarding how HPVs interact with extracellular components to prime virus particles for eventual disassembly and effectuate association with the viral receptor complex. Additionally, I propose a model to account for how epithelial injury and the wound response may actively participate in successful HPV infection of basal epithelial cells.

• Capsid conformational changes
• Epithelial wounding
• HPV16
• Heparan sulfonated proteoglycans
• Keratinocyte signaling
• Oncogenic HPV genotypes
• Papillomavirus infection

Papillomaviruses (PVs) and polyomaviruses (PyVs) infect diverse vertebrates including human and cause a broad spectrum of outcomes from asymptomatic infection to severe disease. There has been no PV and only one PyV detected in tree shrews, though the genomic properties of tree shrews are highly similar to those of the primates.

Swab and organ samples of tree shrews collected in the Yunnan Province of China, were tested by viral metagenomic analysis and random PCR to detect the presence of PVs and PyVs. By PCR amplification using specific primers, cloning, sequencing and assembling, genomes of two PVs and one PyV were identified in the samples.

Two novel PVs and a novel PyV, named tree shrew papillomavirus 1 and 2 (TbelPV1 and TbelPV2) and polyomavirus 1 (TbelPyV1) were characterized in the Chinese tree shrew (Tupaia belangeri chinensis). The genomes of TbelPV1, TbelPV2, and TbelPyV1 are 7410 bp, 7526 bp, and 4982 bp in size, respectively. The TbelPV1 genome contains 7 putative open-reading frames (ORFs) coding for viral proteins E1, E2, E4, E6, E7, L1, and L2; the TbelPV2 genome contains 6 ORFs coding for viral proteins E1, E2, E6, E7, L1, and L2; and the TbelPyV1 genome codes for the typical small and large T antigens of PyV, as well as the VP1, VP2, and VP3 capsid proteins. Genomic comparison and phylogenetic analysis indicated that TbelPV1 and TbelPV2 represented 2 novel PV genera of Papillomaviridae, and TbelPyV1 represented a new species of genus Alphapolyomavirus. Our epidemiologic study indicated that TbelPV1 and TbelPV2 were both detected in oral swabs, while TbelPyV1 was detected in oral swabs and spleens.

Two novel PVs (TbelPV1 and TbelPV2) and a novel PyV (TbelPyV) were discovered in tree shrews and their genomes were characterized. TbelPV1, TbelPV2, and TbelPyV1 have the highest similarity to Human papillomavirus type 63, Ursus maritimus papillomavirus 1, and Human polyomavirus 9, respectively. TbelPV1 and TbelPV2 only showed oral tropism, while TbelPyV1 showed oral and spleen tropism.

The online version of this article (10.1186/s12985-019-1141-9) contains supplementary material, which is available to authorized users.

• Papillomavirus
• Polyomavirus
• Tree shrew
• Tumor virus
• Tupaia belangeri

• AX7 cells
• Angiogenesis
• metastatic liver carcinoma
• rabbit

The purpose of the present work is to establish an ultra-minimal invasive percutaneous puncture inoculation method for a VX2 orthotopic lung cancer rabbit model with fewer technical difficulties, lower mortality of rabbits, a higher success rate and a shorter operation time, to evaluate the growth, metastasis and apoptosis of tumor by CT scans, necropsy, histological examination, flow cytometry and immunohistochemistry. The average inoculation time was 10–15 min per rabbit. The tumor-bearing rate was 100%. More than 90% of the tumor-bearing rabbits showed local solitary tumor with 2–10 mm diameters after two weeks post-inoculation, and the rate of chest seeding was only 8.3% (2/24). The tumors diameters increased to 4–16 mm, and irregularly short thorns were observed 3 weeks after inoculation. Five weeks post-inoculation, the liquefaction necrosis and a cavity developed, and the size of tumor grew further. Before natural death, the CT images showed that the tumors spread to the chest. The flow cytometry and immunohistochemistry indicated that there was less apoptosis in VX2 orthotopic lung cancer rabbit model compared to chemotherapy drug treatment group. Minimal invasive percutaneous puncture inoculation is an easy, fast and accurate method to establish the VX2 orthotopic lung cancer rabbit model, an ideal in situ tumor model similar to human malignant tumor growth.

• Fast method
• Minimal invasive
• Percutaneous puncture inoculation
• VX2 orthotopic lung cancer rabbit model

• clonal amplification
• clonal integration
• oncovirus
• tumor virus
• whole-genome sequencing (WGS)