Oncolytic virotherapy

Host-specific pathogenicity

The family paramyxoviridae contains several important pathogens for humans and domestic animals such as Measles virus, Canine distemper virus (CDV), Rinderpest virus and Nipah virus. Previous studies have revealed that these viruses cause host species-specific pathogenesis. For example, Measles virus causes measles to humans, but causes no disease to mice or dogs. On the other hand, CDV causes no disease to humans, but causes fatal disease to many kinds of wild and domestic animals including dogs and lions. Similarly, Nipah virus causes fatal disease to humans as well as horses and dogs, but causes no disease to bats (See below). Therefore, bats harboring Nipah virus is recognized as infectious sources of outbreaks. We have investigated the causes of different symptoms depending on host animals by analyzing host gene response and virus-host interaction.

Mechanism underlying pathogenesis of virus infection

Previous studies have revealed that viruses replicate in specific types of cells and tissues, and the virus tropism is the major cause of the symptoms unique to the virus. For example, Measles virus infects immune cells, such as lymphoid cells, which causes the transient immunosuppression, and Niaph virus infects neurons and vascular endothelial cells causing encephalitis and multi-organ failure. It has been known that the virus tropism is corelated to the expression pattern of receptor molecules on the cell surface in each tissue types, but the exact mechanism by which viruses efficiently replicate only in the specific cell types has not been clarified. We have investigated this mechanism by analyzing host cell type-specific gene responses and virus-host interactions.

How do viruses exploit host machineries?

Viruses lack information to replicate by themselves, and therefore, they need to exploit machineries in host cells for their replication. The life cycle of paramyxoviruses consists of entry, viral protein expression, replication of viral genome, their assembly and egression of new virions. Functions of each viral protein have not been fully understood, and the elucidation of the mechanisms would lead to the discovery of the novel antiviral mechanism as well as identification of the novel targets for infection control and prevention. We have performed the function analysis of viral products and have published many novel findings.
See the list of past publications here.

It has been known that morbilliviruses, including Measles virus and CDV, induce strong immune response, so called life-long immunity. We have investigated the morbillivirus for many years and are familiar with their characteristics. Besides, we have established the reverse genetics systems to produce recombinant viruses. By taking advantage of these knowledge and technics, we have developed various bivalent vaccines for various viral and parasitic infections using Measles virus as a vector. Especially, the recombinant Nipah virus vaccine using a Measles virus vector was recognized as a promising candidate, and we are currently developing it as the world’s first practical Nipah vaccine together with CEPI (Coalition for Epidemic Preparedness Innovations).

For the detail for CEPI Nipah Vaccine project, please see here.

Through our research history, we found that our HL strain of measles virus had strong cytotoxicity to various types of cancer, including breast cancer. Then, we introduced a genetic modification to the Measles virus strain by reverse genetics method to generate the recombinant Measles virus, called SLAMblind (rMV SLAMblind), which has strong cytotoxicity to cancer cells without causing measles. To date, our results have suggested that rMV SLAMblind has significant anti-tumor effects in tumor-bearing mouse models and is a promising candidate as a novel therapeutic agent for cancer in humans and domestic dogs. We are currently prepaering for clinical research to develop rMV SLAM blind as a novel cancer therapy.