Vesicular stomatitis virus (VSV) is a disease that primarily effects horses, cattle, and swine. Humans can contract this disease by coming in contact with an infected animal. The disease is most often found in North America and Central America. In humans, the symptoms are similar to a flu. The virus replicates quickly and its genome is small and easy to manipulate. Because of this, it has become a useful research tool, as a vaccine platform, and as an oncolytic vector.
There are multiple methods in use to modify viruses such as this. The most important factor in controlling the virus and putting it to use is to have control over the viruses natural ability to replicate. One method to take control over replication is the use of intein splicing. Intein splicing is often a spontaneous biochemical reaction, however, previous research has developed inteins that only undergo splicing in the presence of 4-hydroxytamoxifen.
In vitro Testing
In this way, 4-hydroxytamoxifen can be used as a molecular switch to either prevent or allow splicing to occur. This idea was tested by a team of researchers at Beijing Institute of Biotechnology. After first screening for the most effective intein insertion site, the in vitro replication regulation of the modified virus was assessed. They confirmed that the presence or absence of 4-hydroxytamoxifen directly controlled the replication ability.
In vivo Testing
After seeing the positive results in vitro, they then continued the research in vivo. Laboratory mice were first injected intracerebrally with the modified virus and then also injected intraperitoneally with 4-hydroxytamoxifen. The progression of this experiment was measured using luminescence imaging of the brain. They confirmed that the virus was still controlled in vivo.
This is an exciting improvement in manipulating and controlling a virus so that it may be used as a tool in biological systems. The same idea applied to vesicular stomatitis virus may also be useful in working with various other viruses too.
4-Hydroxytamoxifen is available at LKT Labs:
Zhao Z, Wang B, Wu S, et al. Regulated control of virus replication by 4-hydroxytamoxifen-induced splicing. Front Microbiol. 2023 Mar 13:14:1112580. doi: 10.3389/fmicb.2023.1112580. PMID: 36992923