Did you know elephants can get herpes and die from it?

12 August 2020

Posted by: Mia Rozenbaum

Category: Research & medical benefits

Did you know elephants can get herpes and die from it?  

Herpesviruses are a very broad family which can infect a wide range of animals, and Asian elephants are one of them. But despite nearly two decades of research, the elephant endotheliotropic herpesvirus remains largely unknown. However, scientists have finally discovered where the deadly virus replicates in the body and can now move on to studying the disease in cell cultures. A huge win for an endangered species threatened by more than just this virus.  

When you think herpes, your thoughts don’t immediately go to elephants, and for a reason. Herpesviruses are very common within human populations, causing cold sores and fever blisters on various parts of the body. In the US, about half of human adolescents and adults under the age of 50 are infected with the herpes simplex virus (HSV)-1, and about one in eight are infected with HSV-2. 

So, when you first encounter the virus, it is usually in the form of a small pimple on the corner of a mouth, rather than a deadly disease that can kill elephants. 

Herpesviruses affect a wide range of animals 

The reality is that the herpesvirus family is very large and can affect a wide variety of animals. For instance, the equine herpes virus targets the respiratory, reproductive and central nervous systems, and gradually spreads throughout the body. 

Fortunately, you cannot catch herpes from an elephant or a horse. Each species has its own herpes virus that can cause various symptoms.  

Nine of these viruses infect humans, five of which are extremely widespread. You probably have come across someone with either HSV-1, HSV-2, the varicella zoster virus which causes chickenpox and shingles, the Epstein–Barr virus implicated in several diseases including mononucleosis and some cancers, and the cytomegalovirus - more than 90% of adults have been infected with at least one of these.   

Herpesviruses are known to share six hallmark characteristics: ubiquity, latency, incurability, reactivation, unapparent infection, and opportunistic infection.  

But for juvenile Asian elephants worldwide, a herpesvirus from the subfamily Betaherpesvirinae, called elephant endotheliotropic herpesvirus (EEHV), can be rapidly deadly. For reasons that are not yet understood, approximately 20% of Asian elephant calves appear to be susceptible to the disease when primary infections are not controlled by normal immune responses. 

The elephant herpesvirus can cause a haemorrhagic disease  

The virus causes an acute haemorrhagic disease called elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) which can result in death within 24 hours of infection especially in elephants younger than 8 years old with mortality rate of up to 85%. 

Discovered in 1999, the disease remains largely unknown. Little is known about how it is spread and which part of the body it infects. Much of what underlies EEHV-HD remains uncertain or controversial, including which tissues and cell types are permissive for EEHV infection and replication. This despite extensive analysis of the EEHV’s genome. 

Thai researchers turned to other Betaherpesviruses, such as the Human cytomegaloviruse for answers. The human version infects a broad range of target tissues, including epithelia of the oropharynx, endothelia, and immune cells by attaching to their host cell receptors. Then, it proceeds to replicate its own DNA by producing DNA polymerase, which is a marker of viral infection and replication.  

The scientists had the idea to target that process, using antibody recognition, to identify where the virus was active and which cells were infected. 

Previous studies had already developed antibodies against an envelope protein of EEHV which found the virus in the salivary glands, gastrointestinal epithelia and immune cells of the animals. However, this indicated presence of viral material, dead and alive, including material inside the immune cells, happily munching away and getting rid of the virus, not actual viral activity and replication.  

This 2020 study published in Nature is the first to develop antibodies against a non-structural protein of EEHV to find the actual target cells of the virus in vivo.  

Finding where the virus replicates  

The study demonstrated for the first time that EEHV targeted a broad range of cells in young Asian elephants during acute infection. The rabbit polyclonal antibodiesengineered for the job,indicated that the virus was present throughout the epithelia of the alimentary tract and salivary glands, endothelia and smooth muscle cells including in the cardiovascular system, and immune monocytic lineage cells as well as sometimes in the bone marrow cells.  

This might not seem much but knowing where the virus is active might help better understand how the virus works and spread in the body and ultimately find a treatment to attenuate the symptoms of the disease.  

For instance, the findings reaffirmed the active presence of the virus in the vascular endothelia, particularly small arteries and veins, arteriole, venules and capillaries, similar to that observed in HCMV infections in humans. This strongly suggest that these small blood vessels may express unique cell surface antigens required for EEHV, and thus, play a role in pathogenesis of EEHV-HD. 

Moreover, the study supports the hypothesis that EEHV is transmitted via saliva and intestinal excretion, just like it is for humans. And given that the epithelia of the trunk and tongue of elephants are permissive for EEHV replication, according to the new study, it is reasonable to speculate that this is the site of primary infection.From there, EEHV spreads to other target organs via circulating immune cells in which it replicates, again just like other human and porcine Betaherpesviruses. 

Now that the scientists know where the virus replicates in the body of elephants, they can move on to studying the virus in cell populations. This study is a promising foundation for future breakthroughs that could be crucial for an endangered and declining population of elephants.