Murine respirovirus, now Respirovirus muris, formerly Sendai virus (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is an enveloped, 150–200 nm diameter, negative sense, single-stranded RNA virus of the family Paramyxoviridae. It typically infects rodents and it is not pathogenic for humans or domestic animals. Respirovirus muris is a member of the genus Respirovirus. The virus was isolated in the city of Sendai in Japan in the early 1950s. Since then, it has been actively used in research as a model pathogen. The virus is infectious for many cancer cell lines (see below), and has oncolytic properties demonstrated in animal models and in naturally occurring cancers in animals. Its ability to fuse eukaryotic cells and to form syncytium was used to produce hybridoma cells capable of manufacturing monoclonal antibodies in large quantities. Recent applications of SeV-based vectors include the reprogramming of somatic cells into induced pluripotent stem cells and vaccine creation. For vaccination purpose the Sendai virus-based constructs could be delivered in a form of nasal drops, which may be beneficial in inducing a mucosal immune response. SeV has several features that are important in a vector for a successful vaccine: the virus does not integrate into the host genome, it does not undergo genetic recombination, it replicates only in the cytoplasm without DNA intermediates or a nuclear phase and it does not cause any disease in humans or domestic animals. Sendai virus is used as a backbone for vaccine development against Mycobacterium tuberculosis that causes tuberculosis, against HIV-1 that causes AIDS and against other viruses, including those that cause severe respiratory infections in children. The latter include human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV) and human parainfluenza viruses (HPIV). The vaccine studies against M. tuberculosis, HMPV, HPIV1 and, HPIV2 are in the pre-clinical stage, against HRSV a phase I clinical trial has been completed. The phase I clinical studies of SeV-based vaccination were also completed for HPIV1. They were done in adults and in 1–6-year-old children. As a result of vaccination against HPIV1, a significant boost in virus-specific neutralizing antibodies was observed. A SeV-based vaccine development against HIV-1 has reached a phase II clinical trial. In Japan intranasal Sendai virus-based SARS-CoV-2 vaccine was created and tested in a mouse model. More recent applications (2024–2025) include non-integrative gene delivery for fertility restoration in mouse models, enhanced transduction in pancreatic cancer, and temperature-sensitive platforms for CRISPR-Cas9 editing in human stem cells and viral genome engineering.
As an infection agent SeV replication occurs exclusively in the cytoplasm of the host cell. The virus is using its own RNA polymerase. One replication cycle takes approximately 12–15 hours with one cell yielding thousands of virions.
Susceptible animals The virus is responsible for a highly transmissible respiratory tract infection in mice, hamsters, guinea pigs, rats, and occasionally marmosets, with infection passing through both air and direct contact routes. Natural infection occurs by way of the respiratory tract. In animal facility airborne transmission can occur over a distance of 5–6 feet as well as through air handling systems. The virus can be detected in mouse colonies worldwide, generally in suckling to young adult mice. A study in France reported antibodies to SeV in 17% of mouse colonies examined. Epizootic infections of mice are usually associated with a high mortality rate, while enzootic disease patterns suggest that the virus is latent and can be cleared over the course of a year. Sub-lethal exposure to SeV can promote long-lasting immunity to further lethal doses of SeV. The virus is immunosuppressive and may predispose to secondary bacterial infections. There are no scientific studies, which were performed using modern detection methods, which would identify SeV as an infectious and decease causative for humans or domestic animals.
Variable susceptibility to infection in mouse and rat strains Inbred and outbred mouse and rat strains have very different susceptibility to Sendai virus infection. Visualization of SeV infection in live animals demonstrates this difference. The 129/J mice tested were approximately 25,000-fold more sensitive than SJL/J mice. C57BL/6 mice are highly resistant to the virus, while DBA/2J mice are sensitive. C57BL/6 mice showed slight loss of body weight after SeV administration, which returned to normal later. Only 10% mortality rate was observed in C57BL/6 mice after the administration of very high virulent dose of 1*105 TCID50. It was shown that resistance to the lethal effects of Sendai virus in mice is genetically controlled and expressed through control of viral replication within the first 72 hours of infection. Treatment of both strains with exogenous IFN before and during viral infection led to an increase in survival time in C57BL/6 mice, but all animals of both strains ultimately succumb to SeV caused disease. If a mouse survives a SeV infection, it develops a lifelong immunity to subsequent viral infections. There are SeV-resistant F344 rats and susceptible BN rats.
Course of infection In the host airways the virus titer reaches a peak after 5–6 days post infection initiation that decreases to undetectable levels by day 14. The virus promotes a descending respiratory infection, which begins in the nasal passages, passes through the trachea into the lungs and causes necrosis of the respiratory epithelium. The necrosis is mild in the first few days of infection, but later became severe by peaking around day 5. By day 9, the cells of the surface of the airways regenerate. Focal interstitial pneumonia can developed accompanied by inflammation and lesions of various degrees on the lungs. Usually, the respiratory system shows signs of healing within 3 weeks of infection, however, residual lesions, inflammation, or permanent scarring can occur. 6–8 days after the infection initiation serum antibodies appear. They remain detectable for about 1 year.
Symptoms in animals Source:
Sneezing Hunched posture Respiratory distress Porphyrin discharge from eyes and/or nose Lethargy Failure to thrive in surviving babies and young rats Anorexia
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