Virus-induced Brain Tumor Models

Virus-induced brain tumors model

Due to the discovery of a relationship between viruses and the development of brain tumors, some scholars have attempted to use viruses for brain tumor induction experiments. However, their pathogenesis has not been completely elucidated. The possible mechanism is that the virus itself has a replicative and genetic role, and upon infection of cells releases genetic material that integrates into the host cell genome and causes carcinogenesis. Some viruses carry oncogenes within their genes that encode proteins that contribute to host cell carcinogenesis.

We provide services for the building of viral-induced brain tumors model

Researchers often study brain tumors in virus-free models, but viruses may play an important role in brain tumors. Alfa Cytology can build viral-induced brain tumor models for our customers, which are well suited for studying the effects of radiation/chemotherapy in glioma. Both ribonucleic acid viruses and deoxyribonucleic acid viruses (adenoviruses) can induce brain tumors. Virus-induced brain tumors can be transmitted continuously in homozygous animals and cloned to produce biologically stable models.

Viruses	Induced tumor types	Inducible animals
Rous sarcoma vires (RSV)	It can induce brain tumors, mainly mesenchymal gliomas and sarcomas.	Rats Gopher Canine Monkey
Simian virus40 (SV40)	SV40 is closely associated with the development of human glioma and can be targeted for glioma prevention and treatment. It can induce the production of ventricular meningiomas and choroid plexus tumors, and the tumorigenic effect of the virus is proportional to the amount of inoculum.
Cytomegalovirus (CMV)	In cancer cells with mutations in oncogenes, CMV promotes the development of glioblastoma through the STAT3 signaling pathway.
JC virus (JCV)	Infection can induce a variety of brain tumors, such as cerebellar medulloblastoma, thalamic glioma, ventricular meningioma, meningioma, and pineal tumor.

The type of tumor-induced depends on the site of inoculation and the age of the animal. The convex surface of the brain or the cerebellar earthworm is susceptible to sarcoma, and the subventricular canal is susceptible to glioma. Neonatal animals are more susceptible than adult animals. From the established models of virus-induced brain tumors, it is clear that inbred animals are prone to mimic the biology of human brain tumors. We provide viral-induced brain tumors as both a model to explore the pathogenesis of brain tumors and as a source to study therapeutic models.

General services flow of virus-induced brain tumors model building

This in vitro grown cortical organoid model has a variety of neuronal cells and brain regions, and the in vivo growth and invasion of GBM is closely related to various neuronal cells. The cortical organoid model combines the advantages of three-dimensional matrix gel culture and oscillatory culture to simulate the entire process in vivo starting from embryonic stem cells, growing into the inner, middle and outer germ layers, and then differentiating into neuroepithelial tissue, neural tube structures, and cerebral cortex. The cortical organoid model can maintain the individual genotype and the expression level of functional proteins of the organ, which can be applied to human brain disease research and drug screening.

Culture of cortical organoids

Virus preparation. The virus is cultured, propagated, released, and enriched by ultracentrifugation.
Experimental animal preparation. Independently housed in an animal biosafety level II laboratory.
Virus infection. The infectious dose is determined according to pre-experiments and the virus is injected after light anesthesia.
Model analysis. The analysis indexes included symptom observation (animals were observed for 14 days after infection, and weight change, symptoms, and mortality were recorded), virus detection (major tissues and organs were isolated at a certain time after infection, RNA was extracted, and viral load in tissues was detected by real-time fluorescence quantitative PCR, and viral replication was recorded), and pathological diagnosis (major tissues and organs were isolated at a certain time after infection, and HE staining to observe pathological changes).
Evaluation and validation of animal models.

Case Study - Lentiviral Vector-Induced Glioblastoma Model

Model Introduction

The lentiviral vector-induced glioblastoma model provides a versatile preclinical platform for studying GBM initiation and progression in adult immunocompetent mice. This model utilizes Cre-loxP–controlled lentiviral vectors to deliver activated H-Ras and AKT into a small number of GFAP+ cells in specific brain regions, recapitulating the sporadic nature of human GBM. The model enables region- and cell type–specific oncogene expression, allowing investigation of the cellular origin of GBM and the role of the tumor microenvironment. Incorporation of Tp53 heterozygosity faithfully reproduces key histopathological and molecular hallmarks of human glioblastoma multiforme.

Model Information

Model: Lentiviral Vector-Induced Glioblastoma Model
Animal: GFAP-Cre Tp53+/− Mice
Weight: 18-22 g

Cancer Type: Glioblastoma Multiforme
Age: 8-10 Weeks
Vector System: Cre-loxP–controlled Lentiviral Vectors (Tomo Vectors)

Model Construction

The model is established by stereotaxic injection of Cre-loxP–controlled lentiviral vectors (Tomo vectors) expressing activated H-RasV12 and AKT into the hippocampus of adult GFAP-Cre Tp53+/− mice. Cell inoculum is 0.8 µL of viral mixture (1×10⁸ infectious units) per injection site.

Fig. 1 Workflow of lung cancer brain metastasis CDX model establishment. (Source: Alfa Cytology)

Model Data

Tumorigenicity: Injection of H-RasV12 and AKT lentiviral vectors into the hippocampus of GFAP-Cre Tp53+/− mice results in 100% tumor formation with a median latency of approximately 80 days.
Histopathological Fidelity: Tumors recapitulate human glioblastoma multiforme features, including high cellular density, necrosis with pseudopalisading, nuclear pleomorphism (giant cells), microvascular proliferation, and invasive growth.

Fig. 2 Loss of p53 accelerates tumor formation and reduces survival in the glioma model. Data are presented as mean ± standard error (SEM). (Source: Alfa Cytology)

Viruses are widely used as carcinogens because of their short latency period for tumor production and relatively high rate of brain tumor production with a wide species range. Alfa Cytology can build viral-induced brain tumor models for our customers, please feel free to contact us for your customized services.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.