In a new study, researchers from Southern Methodist University and the University of Texas MD Anderson Cancer Center found that oleandrin can stop the spread of HTLV-1 by targeting a stage in the virus’s replication that has not yet been targeted by existing drugs. Related research results were recently published in the Journal of Antivirals & Antiretrovirals, the paper titled “The The Botanical Glycoside Oleandrin Inhibits Human T-cell Leukemia Virus Type-1 Infectivity and Env-Dependent Virological Synapse Formation.”
Figure 1 Diagram of the chemical structure of oleandrin
The HTLV-1 virus was first discovered in 1980. It belongs to the mammalian type C virus of the subfamily of retroviral oncovirus and is the first retrovirus found to be associated with human diseases. HTLV-1 is mainly transmitted through sexual contact, blood transfusion, vertical mother-to-child transmission, and breastfeeding. Similar to the human immunodeficiency virus HIV, the main target cells of HTLV-1 are also CD4 T cells. Although the virus is related to the HIV virus, most infected people have almost no symptoms, so the virus is little known. It is estimated to infect 10 to 15 million people worldwide. There is no cure or treatment for HTLV-1 infection. Therefore, this study is important for the treatment of HTLV-1 virus infection.
HIV-1 can kill infected T cells, whereas HTLV-1 causes them to divide uncontrollably, which in turn can lead to the development of aggressive leukemia. People infected with HTLV-1 can also develop a progressive neuropathy called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM / TSP). It is a progressive inflammatory disease of the nervous system that can affect a person’s ability to walk and can cause severe symptoms that can lead to coma and even death.
Retroviral particles transcribe their RNA into DNA after entering the cell, thereby replicating themselves within the infected cell. This process is called the retroviral life cycle. The more cells produced by the virus, the more severe the symptoms of those infected with HTLV-1.
The Corresponding author Robert Harrod, associate professor of the Department of Biological Sciences at Southern Methodist University, said, “Our results suggest that oleandrin may limit the spread and spread of HTLV-1 by targeting a unique phase of the retrovirus life cycle. ”
Harrod said, “As shown by HIV-1, oleandrin treatment did not affect the ability of infected cells to produce and release new virus particles. However, the virus particles produced are defective, meaning they contain less encapsulated glycoproteins on their surfaces. This impairs their ability to form viral synapses that allow the virus to spread efficiently between cells.”
In order for virus-infected cells to fuse with uninfected T cells, a so-called “envelope” must be present. It forms the outer layer of HTLV-1 virus particles and binds to receptors on the surface of target cells, allowing the virus to enter cells and spread disease. Without this envelope, the HTLV-1 retrovirus cannot successfully spread to other cells. Oleander can uniquely block the integration of HTLV-1 envelope glycoprotein into mature virus particles released from infected cells.
To confirm that purified oleander or oleander extract inhibits the formation of synapses in HTLV-1 virus, Harrod and his team labeled the cell lines infected with HTLV -1 with green fluorescent protein (GFP), so the cells could be easily identified under a microscope by “green” fluorescence. They placed the cells in the same culture medium as the healthy T cells. T cells infected with HTLV-1 were easily detected because they could observe the connection between the two cells, and then a green fluorescent signal appeared in the newly infected T cells.
The mechanism of oleandrin resistance against HTLV-1 virus is different from the existing highly-active antiretroviral therapy (HAART). Since no HAART drug has been found to be effective against the HTLV-1 virus so far, this new study offers new hope for the development of drugs that resist this virus.
- Tetiana Hutchison et al. The Botanical Glycoside Oleandrin Inhibits Human T-cell Leukemia Virus Type-1 Infectivity and Env-Dependent Virological Synapse Formation. Journal of Antivirals & Antiretrovirals, 2019.