What We Can Learn From Other Poxviruses About Monkeypox

(Posted on Tuesday, June 21, 2022)

Since the eradication of smallpox in 1980, there have been growing concerns that we are not prepared for the next poxvirus pandemic. It is important to remember that smallpox killed millions of people throughout human history.

The variola virus that caused smallpox was not only lethal but also highly contagious. Inhaling droplets from an infected person was the primary route that monkeypox was transmitted, albeit the virus could also spread through direct contact with contaminated objects or surfaces. Symptoms usually began with flu-like symptoms, such as muscle aches, headaches, and a fever. As the infection spread, the digestive tract was commonly implicated, causing nausea, vomiting, and severe backaches.

Like other viral infections, most of these symptoms lasted two to four days. Around the twentieth day of infection, visible lesions appeared on the skin. The rash first appeared on the mucous membranes of the throat, mouth, and tongue. When enlarged lesions ruptured, they released large amounts of the virus, which increasingly infected other skin cells. Depending on which strain of the smallpox virus one was infected with, the fatality rate was anywhere between 1% and 75%.

Now, we are seeing a resurgence of poxvirus infections in humans. Given that we no longer vaccinate against smallpox, much of the world population is not protected against the outstanding threat of other orthopoxviruses, such rabbitpox, deerpox, and not to mention, monkeypox. While smallpox only infected humans, many of these poxviruses are zoonotic in nature. A human case of monkeypox, for example, was first detected in 1970 in what is now the Democratic Republic of Congo. Initial studies reported that animal-to-human transmission of the monkeypox virus was rare and sporadic. However, as humans have increasingly come into contact with rainforests and jungles, human monkeypox has become endemic in several central and west African regions.

How big of a threat is monkeypox? Although there is currently no cause for alarm, this will not always be the case. There are already more than 1,000 confirmed cases of human monkeypox across almost 30 countries that do not normally experience outbreaks, including the United States, United Kingdom, and Canada.

Using a strategy called “ring vaccination”, several countries have begun administering smallpox vaccines to individuals that have been exposed to someone with monkeypox. Although smallpox vaccines are known to be effective against various poxviruses, we do not know exactly how effective they are against monkeypox. At this stage, however, this remains one of the most powerful tools we have to keep case numbers low.

The recent surge of human infections has been linked to two predominant strains of the monkeypox virus, one indigenous to West Africa and the other to Congo Basin. These outbreaks, particularly the West African strain, have produced less severe infections than previous variants. So far, no deaths associated with monkeypox have been reported in the United States or Europe, but this may likely change if the virus reaches more vulnerable populations like immunocompromised individuals or young children.

We should remember that poxviruses are not stable; they evolve with their environment. I have previously written about the coevolution of the myxoma rabbitpox virus and European rabbits exposed to a South American viral strain. While natural selection favored rabbits that could resist infection, this virus increasingly evolved to suppress the immune system of its hosts. Given the rate that rabbits multiply, this host-virus “arms race” continues to change the genome of the myxoma virus.

Over time, genome analyses of newer strains have not only identified several mutations from the original South American myxoma viral strain but also the addition of entirely new gene sequences. These sequences have enabled the expression of novel host range factors, known to enhance viral infection and replication.

Across different poxviruses, the role of host range factors is complex and not well understood. It has been suggested that the expression of specific host range factors can allow viruses to cross over and infect other species. This is what researchers speculate occurred in fall of 2018, when hundreds of Iberian hares suddenly died from rabbitpox. The myxoma-like virus detected in these hares had gained approximately 2,800 new base pairs, compared to a South American rabbitpox strain.

How does a poxvirus gain that much new genetic information? These new genes were likely acquired through a process called DNA recombination. DNA recombination occurs when two closely related viruses simultaneously infect the same cell. During replication, these viruses may swap genetic information, thus creating a new hybrid virus. It is unclear what other poxvirus the myxoma rabbitpox virus interacted with to cause the mutation that led to the infection and subsequent death of the Iberian hares.

For a virus, recombination promotes its survival by creating new genetic traits. However, there is no telling what the consequences of future hybrid poxviruses may be to animal and human health.

We must prepare for the possibility that a zoonotic poxvirus could become a highly infectious human pathogen. Our already-fragile health systems cannot afford to be caught in another global pandemic that we are not prepared for.

First, we need to invest in and expand research on smallpox vaccinations. Smallpox may be gone, but other poxviruses continue to threaten human health. Before cases get too high, we must develop a new generation of vaccines that specifically target emerging strains of monkeypox and widely distribute them not only in countries that are experiencing new outbreaks but also in regions where infections are endemic.

Second, we need to produce antiviral treatments that fight infections early and robustly. As we have learned through the Covid-19 pandemic, it is not enough to simply prevent infections from occurring in the first place; we must also stop the progression of severe infections that could overwhelm hospitals and kill vulnerable populations.

We must heed lessons from pandemics’ past and prioritize pandemic and epidemic preparedness, otherwise, we will continue to suffer constant disruption to our lives and needless deaths.

Read the article on Forbes